WorldWideScience

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 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

    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...

  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. Molecular mechanism of bone formation and regeneration

    Institute of Scientific and Technical Information of China (English)

    Akira Yamaguchi

    2008-01-01

    @@ Bone formation and regeneration are mediated by the coordinate action of various factors. Among these, bone morphogenetic protein (BMP) and runt-related gene 2 (Runx2) play crucial roles in bone formation.

  5. Recombinant human bone morphogenetic protein induces bone formation

    International Nuclear Information System (INIS)

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

  6. Bone formation following implantation of bone biomaterials into extraction sites

    OpenAIRE

    Molly, Liene; Vandromme, Heleen; Quirynen, Marc; Schepers, Evert; Adams, Jessica L; van Steenberghe, Daniel

    2008-01-01

    Background: Adequate bone volume is imperative for the osseointegration of endosseous implants, but post-extraction resorption and remodeling may challenge implant placement. The use of bone biomaterials has been advocated to fill extraction sites and to enhance primary implant stability during osseointegration. The objective of the case series was to evaluate bone formation histologically and biomechanically in extraction sites following implantation of three commercially available bone biom...

  7. Sinonasal Schwannoma with New Bone Formation Expressing Bone Morphogenic Protein

    OpenAIRE

    Satoru Kodama; Tomoyo Okamoto; Masashi Suzuki

    2010-01-01

    Schwannoma is a benign tumor that arises from the sheath of myelinated nerve fibers and may occur in any part of the body. Osteogenesis in schwannoma is extremely rare and, to date, new bone formation in sinonasal schwannoma has not yet been reported. Here, we describe the first reported case of sinonasal schwannoma with new bone formation. The tumor was successfully treated by endoscopic sinus surgery, and the patient showed no evidence of recurrence 24 months postoperatively. Immunohistoche...

  8. Aged human bone marrow stromal cells maintaining bone forming capacity in vivo evaluated using an improved method of visualization

    DEFF Research Database (Denmark)

    Stenderup, Karin; Rosada, Cecilia; Justesen, J;

    2004-01-01

    weeks, the implants were removed and embedded un-decalcified in methyl methacrylate (MMA). Sections were stained histochemically with Goldner's Trichrome stain and immuno-histochemically using human-specific antibodies against known osteogenic markers. Implanted human marrow stromal cells (hMSC) were...... able to form bone in vivo. The donor origin of bone was verified using several human-specific antibodies. Dose-response experiments demonstrated that 5 x 10(5) hMSC per implant gave the maximal bone formation after 8 weeks. No difference in BFC was observed between cells obtained from young (24...... vivo assay for quantifying the bone forming capacity (BFC) and we compared the BFC of osteoblastic cells obtained from young and old donors. Osteoblasts were obtained from human bone marrow stromal cell cultures and implanted subcutaneously in immuno-deficient mice (NOD/LtSz- Prkdc(scid)). After 8...

  9. Molecular mechanisms of bone formation in spondyloarthritis.

    Science.gov (United States)

    González-Chávez, Susana Aideé; Quiñonez-Flores, Celia María; Pacheco-Tena, César

    2016-07-01

    Spondyloarthritis comprise a group of inflammatory rheumatic diseases characterized by its association to HLA-B27 and the presence of arthritis and enthesitis. The pathogenesis involves both an inflammatory process and new bone formation, which eventually lead to ankylosis of the spine. To date, the intrinsic mechanisms of the pathogenic process have not been fully elucidated, and our progress is remarkable in the identification of therapeutic targets to achieve the control of the inflammatory process, yet our ability to inhibit the excessive bone formation is still insufficient. The study of new bone formation in spondyloarthritis has been mostly conducted in animal models of the disease and only few experiments have been done using human biopsies. The deregulation and overexpression of molecules involved in the osteogenesis process have been observed in bone cells, mesenchymal cells, and fibroblasts. The signaling associated to the excessive bone formation is congruent with those involved in the physiological processes of bone remodeling. Bone morphogenetic proteins and Wnt pathways have been found deregulated in this disease; however, the cause for uncontrolled stimulation remains unknown. Mechanical stress appears to play an important role in the pathological osteogenesis process; nevertheless, the association of other important factors, such as the presence of HLA-B27 and environmental factors, remains uncertain. The present review summarizes the experimental findings that describe the signaling pathways involved in the new bone formation process in spondyloarthritis in animal models and in human biopsies. The role of mechanical stress as the trigger of these pathways is also reviewed. PMID:26838262

  10. Understanding coupling between bone resorption and formation

    DEFF Research Database (Denmark)

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

    2013-01-01

    Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these...... lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined...... histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested...

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

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

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

  12. The Hedgehog signalling pathway in bone formation

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Philipp Andre; Ling Ye; Ying-Zi Yang

    2015-01-01

    The Hedgehog (Hh) signalling pathway plays many important roles in development, homeostasis and tumorigenesis. The critical function of Hh signalling in bone formation has been identified in the past two decades. Here, we review the evolutionarily conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development, homeostasis and diseases. In the early stages of embryonic limb development, Sonic Hedgehog (Shh) acts as a major morphogen in patterning the limb buds. Indian Hedgehog (Ihh) has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium. Hh signalling is also involved intramembrane ossification. Interactions between Hh and Wnt signalling regulate cartilage development, endochondral bone formation and synovial joint formation. Hh also plays an important role in bone homeostasis, and reducing Hh signalling protects against age-related bone loss. Disruption of Hh signalling regulation leads to multiple bone diseases, such as progressive osseous heteroplasia. Therefore, understanding the signalling mechanisms and functions of Hh signalling in bone development, homeostasis and diseases will provide important insights into bone disease prevention, diagnoses and therapeutics.

  13. Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model.

    Science.gov (United States)

    Lee, Jae Yeon; Son, Soo Jin; Son, Jun Sik; Kang, Seong Soo; Choi, Seok Hwa

    2016-01-01

    Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone) (PCL), β-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: group 1 (control), group 2 (PCL/PLGA hybrid scaffolds), group 3 (PCL/PLGA/TCP hybrid scaffolds), and group 4 (PCL/PLGA/DB hybrid scaffolds). A 5 mm critical defect was induced in the diaphysis of the left radius. X-ray, micro-CT, and histological analyses were conducted at (time 0) 4, 8, and 12 weeks after implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin) were measured and oxidative stress status was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius by inducing repair, suggesting that it could be a good option for the treatment of fracture. PMID:27042660

  14. Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model

    Directory of Open Access Journals (Sweden)

    Jae Yeon Lee

    2016-01-01

    Full Text Available Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone (PCL, β-tricalcium phosphate (TCP, and poly(lactic-co-glycolic acid (PLGA are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: group 1 (control, group 2 (PCL/PLGA hybrid scaffolds, group 3 (PCL/PLGA/TCP hybrid scaffolds, and group 4 (PCL/PLGA/DB hybrid scaffolds. A 5 mm critical defect was induced in the diaphysis of the left radius. X-ray, micro-CT, and histological analyses were conducted at (time 0 4, 8, and 12 weeks after implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin were measured and oxidative stress status was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius by inducing repair, suggesting that it could be a good option for the treatment of fracture.

  15. Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model

    Science.gov (United States)

    Lee, Jae Yeon; Son, Soo Jin; Son, Jun Sik; Kang, Seong Soo; Choi, Seok Hwa

    2016-01-01

    Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone) (PCL), β-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: group 1 (control), group 2 (PCL/PLGA hybrid scaffolds), group 3 (PCL/PLGA/TCP hybrid scaffolds), and group 4 (PCL/PLGA/DB hybrid scaffolds). A 5 mm critical defect was induced in the diaphysis of the left radius. X-ray, micro-CT, and histological analyses were conducted at (time 0) 4, 8, and 12 weeks after implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin) were measured and oxidative stress status was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius by inducing repair, suggesting that it could be a good option for the treatment of fracture. PMID:27042660

  16. 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......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...... patients 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....

  17. Dissociation of bone formation markers in bone metastasis of prostate cancer.

    OpenAIRE

    Koizumi, M; Maeda, H.; Yoshimura, K; Yamauchi, T.; Kawai, T.; Ogata, E

    1997-01-01

    To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression...

  18. Brief Review of Models of Ectopic Bone Formation

    OpenAIRE

    Scott, Michelle A.; Levi, Benjamin; Askarinam, Asal; Nguyen, Alan; Rackohn, Todd; Ting, Kang; Soo, Chia; James, Aaron W.

    2011-01-01

    Ectopic bone formation is a unique biologic entity—distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used f...

  19. Macrophage Polarization and Bone Formation: A review.

    Science.gov (United States)

    Horwood, Nicole J

    2016-08-01

    The contribution of inflammation to bone loss is well documented in arthritis and other diseases with an emphasis on how inflammatory cytokines promote osteoclastogenesis. Macrophages are the major producers of cytokines in inflammation, and the factors they produce depend upon their activation state or polarization. In recent years, it has become apparent that macrophages are also capable of interacting with osteoblasts and their mesenchymal precursors. This interaction provides growth and differentiation factors from one cell that act on the other and visa versa-a concept akin to the requirement for a feeder layer to grow hemopoietic cells or the coupling that occurs between osteoblasts and osteoclasts to maintain bone homeostasis. Alternatively, activated macrophages are the most likely candidates to promote bone formation and have also been implicated in the tissue repair process in other tissues. In bone, a number of factors, including oncostatin M, have been shown to promote osteoblast formation both in vitro and in vivo. This review discusses the different cell types involved, cellular mediators, and how this can be used to direct new bone anabolic approaches. PMID:26498771

  20. 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...... are added as in the contact precipitation process. The results show that the columns are able to remove up to 700 bedvolumes, before the concentration of fluoride in the effluent water breaks through, above 1.5 mg/L. Operational removal capacities observed are 7 and 9 mg/L, depending on contact time...... 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...

  1. 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......) from human osteoclasts cultured on either bone or plastic, and tested their effects on bone nodule formation by osteoblasts. Both types of CM were shown to dose-dependently induce bone nodule formation, whereas non-conditioned osteoclast culture medium had no effects. These data show that osteoclasts...

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

    International Nuclear Information System (INIS)

    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.)

  3. [The new bone formation and bone metabolism in Forestier disease].

    Science.gov (United States)

    Kotrych, Daniel; Bohatyrewicz, Andrzej; Woźniak, Wojciech; Zietek, Paweł; Kołodziej, Łukasz; Karaczun, Maciej; Grzegorczyk, Wojciech; Antoniak, Krzysztof

    2008-01-01

    The study was performed on 36 male patients between 65 and 83 years who were either hospitalised or treated in the out-patients clinic due to Forestier's disease. The aim of the study was to evaluate the advance of ectopic bone formation process in cervical spine and bony metabolic changes in treated patients. The study showed reverse corelation between the degree of advance of cervical hyperostosis and the prevalence of osteoporosis and metabolic disorders in the tested group. The authors have emphasized the need of precise evaluation and differentiation of Forestier's disease and degenerative spine disease. PMID:18847002

  4. Mechanical loading, damping, and load-driven bone formation in mouse tibiae.

    Science.gov (United States)

    Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki

    2012-10-01

    Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect

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

    OpenAIRE

    Duong, Le T.

    2012-01-01

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

  6. The Effect of Bone Loss Pattern on the Structural Capacity of the Proximal Femur

    Institute of Scientific and Technical Information of China (English)

    FAN Li-xia; Eric Wang

    2006-01-01

    The effect of age-related bone loss on the structural capacity of the proximal femur were investigated by Finite Element Analysis(FEA). Four bone loss patterns were considered. These were "uniform cortical bone loss", "neck cortical bone loss", "intertrochanteric cortical bone loss" and "uniform trabecular bone loss". The results show that the two "non-uniform cortical bone loss" patterns are more dangerous than the "uniform cortical bone loss" pattern, and that the cortical bone loss in intertrochanteric region is associated with a greater reduction in cortical failure load than the cortical bone loss in the femoral neck. The trabecular bone loss causes a limited decrease in both cortical failure and trabecular failure loads. This research should be helpful to the clinical assessment of femur fracture risk due to age-related bone loss.

  7. Effect of spaceflight on periosteal bone formation in rats

    Science.gov (United States)

    Wronski, T. J.; Morey, E. R.

    1983-01-01

    Male Wistar rats were placed in orbit for 18.5 days aboard the Soviet COSMOS 1129 biological satellite. Tetracycline was administered before and after spaceflight to label areas of bone formation. An inhibition of periosteal bone formation occurred during spaceflight in the tibial and humeral diaphyses, but this defect was corrected during the postflight period. The increased extent of arrest lines at these skeletal sites suggested that periosteal bone formation may have even ceased during spaceflight. The rib exhibited a small but nonsignificant decrease in periosteal bone formation. Endosteal bone resorption was not affected markedly by spaceflight conditions. The observed inhibition of periosteal bone formation may be a result of mechanical unloading, but endocrine factors cannot be ruled out.

  8. 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

    BACKGROUND: Harvesting techniques can affect cellular parameters of autogenous bone grafts in vitro. Whether these differences translate to in vivo bone formation, however, remains unknown. OBJECTIVE: The purpose of this study was to assess the impact of different harvesting techniques on bone fo...

  9. The impact of skeletal unloading on bone formation

    Science.gov (United States)

    Bikle, Daniel D.; Sakata, Takeshi; Halloran, Bernard P.

    2003-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.

  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; Clasen-Linde, Erik; Salomo, Morten; Levin Andersen, Thomas

    2015-01-01

    . Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell......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...... 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 that a...

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

    OpenAIRE

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

    2015-01-01

    Background 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. Methods The immature rabbit tibial DO model (20 mm length-gain) was u...

  12. Brief review of models of ectopic bone formation.

    Science.gov (United States)

    Scott, Michelle A; Levi, Benjamin; Askarinam, Asal; Nguyen, Alan; Rackohn, Todd; Ting, Kang; Soo, Chia; James, Aaron W

    2012-03-20

    Ectopic bone formation is a unique biologic entity--distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success. PMID:22085228

  13. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

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

    Science.gov (United States)

    Moreau, Nathan; Charrier, Jean-Baptiste

    2015-03-01

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

  15. 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.

  16. Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model

    OpenAIRE

    Jae Yeon Lee; Soo Jin Son; Jun Sik Son; Seong Soo Kang; Seok Hwa Choi

    2016-01-01

    Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone) (PCL), β-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing betwe...

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

    International Nuclear Information System (INIS)

    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.

  18. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.

    OpenAIRE

    Belfrage Ola; Isaksson Hanna; Tägil Magnus

    2012-01-01

    ABSTRACT: BACKGROUND: Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone...

  19. Vascular biology and bone formation: hints from HIF

    OpenAIRE

    Towler, Dwight A.

    2007-01-01

    In this issue of the JCI, Wang, Clemens, and colleagues demonstrate that hypoxia-inducible factor α (HIFα) signaling in bone-building osteoblasts is central to the coupling of angiogenesis and long bone development in mice (see the related article beginning on page 1616). They show that bone formation controlled by osteoblast HIFα signaling is not cell autonomous but is coupled to skeletal angiogenesis dependent upon VEGF signaling. Thus, strategies that promote HIFα signaling in osteoblasts ...

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

    Science.gov (United States)

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

    2014-01-10

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

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

    International Nuclear Information System (INIS)

    Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45Ca 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

  2. Stimulation of bone marrow cells and bone formation by nacre: in vivo and in vitro studies.

    Science.gov (United States)

    Lamghari, M; Almeida, M J; Berland, S; Huet, H; Laurent, A; Milet, C; Lopez, E

    1999-08-01

    There is frequently a loss of vertebral bone due to disease or aging. Nacre (mother of pearl from the oyster Pinctada maxima) stimulates bone cell differentiation and bone formation in vitro and in vivo. Experimental bone defects were prepared in the vertebrae of sheep and used to test the suitability of nacre as an injectable osteogenic biomaterial for treating vertebral bone loss. Twenty-one cavities were prepared in the first four upper lumbar vertebrae of 11 sheep and filled with nacre powder. The lumbar vertebrae were removed after 1 to 12 weeks, embedded undecalcified in methacrylate, and processed for histological studies. The nacre slowly dissolved and the experimental cavities contained a large active cell population. By 12 weeks, the experimental cavity was occupied by newly matured bone trabeculae in contact with or adjacent to the dissolving nacre. The functional new bone trabeculae were covered with osteoid lined with osteoblasts, indicating continuing bone formation. The in vitro study on rat bone marrow explants cultured with a water-soluble extract of the nacre organic matrix also resulted in the stimulation of osteogenic bone marrow cells with enhanced alkaline phosphatase activity. Thus, both the in vivo and in vitro findings suggest that nacre contains one or more signal molecules capable of activating osteogenic bone marrow cells. PMID:10458284

  3. Iron deficiency anemia's effect on bone formation in zebrafish mutant.

    Science.gov (United States)

    Bo, Lin; Liu, Zhichun; Zhong, Yingbin; Huang, Jian; Chen, Bin; Wang, Han; Xu, Youjia

    2016-07-01

    Iron is one of the essential elements of life. Iron metabolism is related to bone metabolism. Previous studies have confirmed that iron overload is a risk factor for osteoporosis. But the correlation between iron deficiency and bone metabolism remains unclear. Ferroportin 1 is identified as a cellular iron exporter and required for normal iron cycling. In zebrafish, the mutant of ferroportin 1 gene (fpn1), weh(tp85c) exhibited the defective iron transport, leading to developing severe hypochromic anemia. We used weh(tp85c) as a model for investigating iron deficiency and bone metabolism. In this study, we examined the morphology of the developing cartilage and vertebrae of the Weh(tp85) compared to the wild type siblings by staining the larvae with alcian blue for cartilage and alizarin red for the bone. In addition, we evaluated the expression patterns of the marker genes of bone development and cell signaling in bone formation. Our results showed that weh(tp85c) mutant larvae exhibited the defects in bone formation, revealing by decreases in the number of calcified vertebrae along with decreased expression of osteoblast novel genes: alpl, runx2a and col1a1a and BMPs signaling genes in osteoblast differentiation: bmp2a and bmp2b. Our data suggest that iron deficiency anemia affects bone formation, potentially through the BMPs signaling pathway in zebrafish. PMID:27184405

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

    Science.gov (United States)

    Stein, Koen; Prondvai, Edina

    2014-02-01

    We present novel findings on sauropod bone histology that cast doubt on general palaeohistological concepts concerning the true nature of woven bone in primary cortical bone and its role in the rapid growth and giant body sizes of sauropod dinosaurs. By preparing and investigating longitudinal thin sections of sauropod long bones, of which transverse thin sections were published previously, we found that the amount of woven bone in the primary complex has been largely overestimated. Using comparative cellular and light-extinction characteristics in the two section planes, we revealed that the majority of the bony lamina consists of longitudinally organized primary bone, whereas woven bone is usually represented only by a layer a few cells thin in the laminae. Previous arguments on sauropod biology, which have been based on the overestimated amount, misinterpreted formation process and misjudged role of woven bone in the plexiform bone formation of sauropod dinosaurs, are thereby rejected. To explain the observed pattern in fossil bones, we review the most recent advances in bone biology concerning bone formation processes at the cellular and tissue levels. Differentiation between static and dynamic osteogenesis (SO and DO) and the revealed characteristics of SO- versus DO-derived bone tissues shed light on several questions raised by our palaeohistological results and permit identification of these bone tissues in fossils with high confidence. By presenting the methods generally used for investigating fossil bones, we show that the major cause of overestimation of the amount of woven bone in previous palaeohistological studies is the almost exclusive usage of transverse sections. In these sections, cells and crystallites of the longitudinally organized primary bone are cut transversely, thus cells appear rounded and crystallites remain dark under crossed plane polarizers, thereby giving the false impression of woven bone. In order to avoid further confusion in

  5. The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

    NARCIS (Netherlands)

    E. Maronde (Erik); A.F. Schilling (Arndt); S. Seitz (Sebastian); T. Schinke (Thorsten); I. Schmutz (Isabelle); G.T.J. van der Horst (Gijsbertus); M. Amling (Michael); U. Albrecht (Urs)

    2010-01-01

    textabstractBackground: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To

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

    International Nuclear Information System (INIS)

    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 Relation between Bone and Stone Formation

    OpenAIRE

    Krieger, Nancy S.; Bushinsky, David A.

    2012-01-01

    Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total body calcium. The source of this additional urine calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD) which is correlated with the increase in urine calcium excretion. ...

  8. Dried plum's unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model.

    Directory of Open Access Journals (Sweden)

    Elizabeth Rendina

    Full Text Available Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.

  9. Osteogenesis Capacity of a Novel BMP/α-TCP Bioactive Composite Bone Cement

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-zhong; ZHOU Da-li; YIN Shao-ya; YIN Guang-fu; GAO Li-da; ZHANG Yun

    2004-01-01

    To improve the osteogenesis ability of α-tricalcium phosphate (α-TCP) bone cement,a novel BMP/α-TCP composite bone cement was prepared.By measuring the setting time and compressive strength,the hydration characteristic of bone cement was evaluated.Animal experiments including histological observation,radiographic investigation as well as digital image analyses reveal the difference of osteogenesis ability among BMP,α-TCP bone cement and BMP/α-TCP composite bone cement.Results show that α-TCP bone cement possesses excellent hydration and setting properties as well as high mechanical property.Comparison experiments show that BMP/α-TCP composite bone cement has a stronger osteogenesis ability.The gross observation of the implant site does not exhibit any inflammation or necrosis.Histological analyses reveal that the material has good osteointegration with host bone,and new bone formation is detected within the materials,which are degrading.Strong osteogenesis ability of the composite is due to not only the excellent osteoconductive potential but also the osteoinductive potential contributed by active BMP releasing and the material degradation.Large skull defect could be well-healed by filling BMP/α-TCP composite bone cement.This novel material proves itself to be an absorbable and bioactive bone cement with an osteogenesis ability.

  10. Nonlinear pattern formation in bone growth and architecture

    Directory of Open Access Journals (Sweden)

    Phil eSalmon

    2015-01-01

    Full Text Available The 3D morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatio-temporal 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 nonlinear 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 simulation of bone modeling.What insights has NPF provided to bone biology? One example concerns the genetic disorder Juvenile Pagets Disease (JPD 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 consequence of the

  11. Reduced supportive capacity of bone marrow stroma upon chemotherapy is mediated via changes in glycosaminoglycan profile

    NARCIS (Netherlands)

    Zweegman, Sonja; Kessler, Floortje L.; Kerkhoven, Ron M.; Heimerikx, Mike; Celie, Johanna W. A. M.; Janssen, Jeroen J. W. M.; Huijgens, Peter C.; Drager, Angelika M.; Van den Born, Jacob

    2007-01-01

    High dose chemotherapy and radiation have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. We now provide evidence for an important role of chemotherapy-induced alterations in stromal glycosaminoglycans (GAGs) in reduction of the supportive properties of stromal fibr

  12. Surface microcracks signal osteoblasts to regulate alignment and bone formation.

    Science.gov (United States)

    Shu, Yutian; Baumann, Melissa J; Case, Eldon D; Irwin, Regina K; Meyer, Sarah E; Pearson, Craig S; McCabe, Laura R

    2014-11-01

    Microcracks are present in bone and can result from fatigue damage due to repeated, cyclically applied stresses. From a mechanical point, microcracks can dissipate strain energy at the advancing tip of a crack to improve overall bone toughness. Physiologically, microcracks are thought to trigger bone remodeling. Here, we examine the effect of microcracks specifically on osteoblasts, which are bone-forming cells, by comparing cell responses on microcracked versus non-microcracked hydroxyapatite (HA) specimens. Osteoblast attachment was found to be greater on microcracked HA specimens (pmicrocracks on HA. Cells also displayed a preferential attachment that was 75 to 90 μm away from the microcrack indent. After 21 days of culture, osteoblast maturation was notably enhanced on the HA with microcracks, as indicated by increased alkaline phosphatase activity and gene expression. Furthermore, examination of bone deposition by confocal laser scanning microscopy indicated preferential mineralization at microcrack indentation sites. Dissolution studies indicate that the microcracks increase calcium release, which could contribute to osteoblast responses. Our findings suggest that microcracks signal osteoblast attachment and bone formation/healing. PMID:25280696

  13. AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass.

    Science.gov (United States)

    Shah, M; Kola, B; Bataveljic, A; Arnett, T R; Viollet, B; Saxon, L; Korbonits, M; Chenu, C

    2010-08-01

    Adenosine 5'-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cultured in the presence of AMPK activators (AICAR and metformin), AMPK inhibitor (compound C), the gastric peptide hormone ghrelin and the beta-adrenergic blocker propranolol. AMPK activity was measured in cell lysates by a functional kinase assay and AMPK protein phosphorylation was studied by Western Blotting using an antibody recognizing AMPK Thr-172 residue. We demonstrated that treatment of ROS 17/2.8 cells with AICAR and metformin stimulates Thr-172 phosphorylation of AMPK and dose-dependently increases its activity. In contrast, treatment of ROS 17/2.8 cells with compound C inhibited AMPK phosphorylation. Ghrelin and propranolol dose-dependently increased AMPK phosphorylation and activity. Cell proliferation and alkaline phosphatase activity were not affected by metformin treatment while AICAR significantly inhibited ROS 17/2.8 cell proliferation and alkaline phosphatase activity at high concentrations. To study the effect of AMPK activation on bone formation in vitro, primary osteoblasts obtained from rat calvaria were cultured for 14-17days in the presence of AICAR, metformin and compound C. Formation of 'trabecular-shaped' bone nodules was evaluated following alizarin red staining. We demonstrated that both AICAR and metformin dose-dependently increase trabecular bone nodule formation, while compound C inhibits bone formation. When primary osteoblasts were co-treated with AICAR and compound C, compound C suppressed the stimulatory effect of AICAR on bone nodule formation

  14. EFFECT OF CALCIUM ADDITION ON THE DEFLUORIDATION CAPACITY OF BONE CHAR

    DEFF Research Database (Denmark)

    Jacobsen, P.; Dahi, Elian

    1997-01-01

    Dosage of small amounts of calcium chloride to fluoride water prior to contact with bone char which has already been saturated with fluoride is shown to provide an additional fluoride removal capacity. The additionally obtained removal capacity increases with slower filtration velocities and...... capable of reducing the fluoride concentration form 10 to about 0.5 mgF/L. The additionally saturated column is shown to be regenerated by simple adjustment of the pH of the water to 11 and allowing to flow for a few bed volumes. The useful regeneration capacity, where the fluoride concentration is...

  15. Effects of Cadmium on BMP Induced Bone Formation

    Institute of Scientific and Technical Information of China (English)

    陈秋生; 徐顺清

    2003-01-01

    To demonstrate the direct effects of cadmium on activities of bone morphogenetic protein (BMP), a complex containing BMP and cadmium chloride (CdCl2) was implanted beneath the abdominal skin of young male Wistar rats. The activity of BMP was studied by observing the histological changes, and measuring the activity of alkaline phosphatase (ALP) and acid phosphatase (ACP) and calcium content of the implants at different time points. Our results showed that during bone formation induced by BMP, cadmium inhibited the activities of osteoblasts and osteoclasts, and slowed the deposition of calcium. It is concluded that cadmium can directly affect biological activities of BMP directly.

  16. 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....... The aim was to demonstrate that a parenteral formulation of GLP-2 is safe and well tolerated after repeated dosing in healthy postmenopausal women for 14 days. It was further investigated whether the effects on bone turnover markers were sustained throughout the study period. The study was a double...

  17. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2.

    Science.gov (United States)

    Igai, Hitoshi; Chang, Sung Soo; Gotoh, Masashi; Yamamoto, Yasumichi; Yamamoto, Masaya; Tabata, Yasuhiko; Yokomise, Hiroyasu

    2008-01-01

    We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 microg BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 microg BMP-2 from gelatin. PMID:18204324

  18. 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. PMID:24045646

  19. BMP-13 Emerges as a Potential Inhibitor of Bone Formation

    Directory of Open Access Journals (Sweden)

    Bojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan

    2009-01-01

    Full Text Available Bone morphogenetic protein-13 (BMP-13 plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP expression and activity, proteoglycan (PG synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation.

  20. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

    NARCIS (Netherlands)

    Song, G.; Habibovic, P.; Bao, C.; Hu, J.; Blitterswijk, van C.A.; Yuan, H.; Chen, W.; Xu, H.H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagl

  1. 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.

  2. Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.

    Science.gov (United States)

    Arai, Yuki; Aoki, Kazuhiro; Shimizu, Yasuhiro; Tabata, Yasuhiko; Ono, Takashi; Murali, Ramachandran; Mise-Omata, Setsuko; Wakabayashi, Noriyuki

    2016-07-01

    Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone. PMID:27118173

  3. 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

  4. Bone Tissue Engineering with Multilayered Scaffolds-Part II: Combining Vascularization with Bone Formation in Critical-Sized Bone Defect.

    Science.gov (United States)

    Sathy, Binulal Nelson; Watson, Brendan M; Kinard, Lucas A; Spicer, Patrick P; Dahlin, Rebecca L; Mikos, Antonios G; Nair, Shantikumar

    2015-10-01

    Our previous in vivo study showed that multilayered scaffolds made of an angiogenic layer embedded between an osteogenic layer and an osteoconductive layer, with layer thickness in the 100-400 μm range, resulted in through-the-thickness vascularization of the construct even in the absence of exogenous endothelial cells. The angiogenic layer was a collagen-fibronectin gel, and the osteogenic layer was made from nanofibrous polycaprolactone while the osteoconductive layer was made either from microporous hydroxyapatite or microfibrous polycaprolactone. In this follow-up study, we implanted these acellular and cellular multilayered constructs in critical-sized rat calvarial defects and evaluated their vascularization and bone formation potential. Vascularization and bone formation at the defect were evaluated and quantified using microcomputed tomography (microCT) followed by perfusion of the animals with the radio opaque contrast agent, MICROFIL. The extent of bony bridging and union within the critical-sized defect was evaluated using a previously established scoring system from the microCT data set. Similarly the new bone formation in the defect was quantified from the microCT data set as previously reported. Histological evaluation at 4 and 12 weeks validated the microCT findings. Our experimental results showed that acellular multilayered scaffolds with microscale-thick nanofibers and porous ceramic discs with angiogenic zone at their interface can regenerate functional vasculature and bone similar to that of cellular constructs in critical-sized calvarial defects. This result suggests that suitably bioengineered acellular multilayered constructs can be an improved and more translational approach in functional in vivo bone regeneration. PMID:26262560

  5. 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

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a

  6. In vivo ectopic bone formation by devitalized mineralized stem cell carriers produced under mineralizing culture condition.

    Science.gov (United States)

    Chai, Yoke Chin; Geris, Liesbet; Bolander, Johanna; Pyka, Grzegorz; Van Bael, Simon; Luyten, Frank P; Schrooten, Jan

    2014-12-01

    Functionalization of tissue engineering scaffolds with in vitro-generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem cells in vitro. However, the bone-forming capacity of these constructs (seeded with or without cells) is so far not apparent. In this study, we aimed at developing a mineralizing culture condition to biofunctionalize three-dimensional (3D) porous scaffolds with highly mineralized ECM in order to produce devitalized, osteoinductive mineralized carriers for human periosteal-derived progenitors (hPDCs). For this, three medium formulations [i.e., growth medium only (BM1), with ascorbic acid (BM2), and with ascorbic acid and dexamethasone (BM3)] supplemented with calcium (Ca(2+)) and phosphate (PO4 (3-)) ions simultaneously as mineralizing source were investigated. The results showed that, besides the significant impacts on enhancing cell proliferation (the highest in BM3 condition), the formulated mineralizing media differentially regulated the osteochondro-related gene markers in a medium-dependent manner (e.g., significant upregulation of BMP2, bone sialoprotein, osteocalcin, and Wnt5a in BM2 condition). This has resulted in distinguished cell populations that were identifiable by specific gene signatures as demonstrated by the principle component analysis. Through devitalization, mineralized carriers with apatite crystal structures unique to each medium condition (by X-ray diffraction and SEM analysis) were obtained. Quantitatively, BM3 condition produced carriers with the highest mineral and collagen contents as well as human-specific VEGF proteins, followed by BM2 and BM1 conditions. Encouragingly, all mineralized carriers (after reseeded with hPDCs) induced bone formation after 8 weeks of subcutaneous implantation in nude mice models, with BM2-carriers inducing the highest bone volume, and the lowest in the BM3 condition (as quantitated by nano-computed tomography

  7. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats

    Directory of Open Access Journals (Sweden)

    Belfrage Ola

    2012-12-01

    Full Text Available Abstract Background Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. Methods Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. Results In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007. In all groups receiving zoledronic acid, the BV/TV was higher compared to control. Conclusions This study found a strong inhibitory effect on bone resorption by

  8. VEGF stimulates intramembranous bone formation during craniofacial skeletal development.

    Science.gov (United States)

    Duan, Xuchen; Bradbury, Seth R; Olsen, Bjorn R; Berendsen, Agnes D

    2016-01-01

    Deficiency of vascular endothelial growth factor A (VEGF) has been associated with severe craniofacial anomalies in both humans and mice. Cranial neural crest cell (NCC)-derived VEGF regulates proliferation, vascularization and ossification of cartilage and membranous bone. However, the function of VEGF derived from specific subpopulations of NCCs in controlling unique aspects of craniofacial morphogenesis is not clear. In this study a conditional knockdown strategy was used to genetically delete Vegfa expression in Osterix (Osx) and collagen II (Col2)-expressing NCC descendants. No major defects in calvaria and mandibular morphogenesis were observed upon knockdown of VEGF in the Col2(+) cell population. In contrast, loss of VEGF in Osx(+) osteoblast progenitor cells led to reduced ossification of calvarial and mandibular bones without affecting the formation of cartilage templates in newborn mice. The early stages of ossification in the developing jaw revealed decreased initial mineralization levels and a reduced thickness of the collagen I (Col1)-positive bone template upon loss of VEGF in Osx(+) precursors. Increased numbers of proliferating cells were detected within the jaw mesenchyme of mutant embryos. Explant culture assays revealed that mandibular osteogenesis occurred independently of paracrine VEGF action and vascular development. Reduced VEGF expression in mandibles coincided with increased phospho-Smad1/5 (P-Smad1/5) levels and bone morphogenetic protein 2 (Bmp2) expression in the jaw mesenchyme. We conclude that VEGF derived from Osx(+) osteoblast progenitor cells is required for optimal ossification of developing mandibular bones and modulates mechanisms controlling BMP-dependent specification and expansion of the jaw mesenchyme. PMID:26899202

  9. 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. PMID:26491794

  10. Imaging symptomatic bone morphogenetic protein-2-induced heterotopic bone formation within the spinal canal: case report.

    Science.gov (United States)

    Chryssikos, Timothy; Crandall, Kenneth M; Sansur, Charles A

    2016-05-01

    Heterotopic bone formation within the spinal canal is a known complication of bone morphogenetic protein-2 (BMP-2) and presents a clinical and surgical challenge. Imaging modalities are routinely used for operative planning in this setting. Here, the authors present the case of a 59-year-old woman with cauda equina syndrome following intraoperative BMP-2 administration. Plain film myelographic studies showed a region of severe stenosis that was underappreciated on CT myelography due to a heterotopic bony lesion mimicking the dorsal aspect of a circumferentially patent thecal sac. When evaluating spinal stenosis under these circumstances, it is important to carefully consider plain myelographic images in addition to postmyelography CT images as the latter may underestimate the true degree of stenosis due to the potentially similar radiographic appearances of evolving BMP-2-induced heterotopic bone and intrathecal contrast. Alternatively, comparison of sequentially acquired noncontrast CT scans with CT myelographic images may also assist in distinguishing BMP-2-induced heterotopic bony lesions from the thecal sac. Further studies are needed to elucidate the roles of the available imaging techniques in this setting and to characterize the connection between the radiographic and histological appearances of BMP-2-induced heterotopic bone. PMID:26824586

  11. 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.

  12. New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

    Institute of Scientific and Technical Information of China (English)

    Sakae Tanaka; Taiji Adachi; Tatsuhiko Kuroda; Toshitaka Nakamura; Masataka Shiraki; Toshitsugu Sugimoto; Yasuhiro Takeuchi; Mitsuru Saito; John P Bilezikian

    2014-01-01

    Daily 20-mg and once-weekly 56.5-mg teriparatide (parathyroid hormone 1–34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

  13. Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded) allograft

    NARCIS (Netherlands)

    Eniwumide, J.O.; Yuan, H.; Cartmell, S.H.; Meijer, G.J.; Bruijn, J.D. de

    2007-01-01

    Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as co

  14. Bone Formation Process of β-TCP Ceramics with Tetracycline Tracing

    Institute of Scientific and Technical Information of China (English)

    DAI Hong-lian; LI Shi-pu; LU Xu-hui; WANG Xin-yu

    2004-01-01

    To study the new bone formation in the bone defect area after implantation, the tetracycline tracing method was used. The results show that new bone formed in 1 month, and the formation rate of new bone was very high (8.164μm/day),considerably faster than that of control groups (3.219μm/day).The new bone grew up quickly and βTCP particles were surrounded by double fluorescence bands which became more obvious. The new bone formation rate was maximal at 2 months, and then gradually reduced. The rate was steady at 4 months, and then reduced to resembling as the normal physiologic metabolism of bone, which indicated the implanted materials were completely replaced by bone. Calcium phosphatematerials had the ability of osteoconduction.

  15. Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded allograft

    Directory of Open Access Journals (Sweden)

    J O Eniwumide

    2007-08-01

    Full Text Available Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP and tricalcium phosphate (TCP, respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated.

  16. Surface microcracks signal osteoblasts to regulate alignment and bone formation

    OpenAIRE

    Shu, Yutian; Melissa J. Baumann; Case, Eldon D.; Irwin, Regina K.; Meyer, Sarah E.; Pearson, Craig S.; McCabe, Laura R.

    2014-01-01

    Microcracks are present in bone and can result from fatigue damage due to repeated, cyclically applied stresses. From a mechanical point, microcracks can dissipate strain energy at the advancing tip of a crack to improve overall bone toughness. Physiologically, microcracks are thought to trigger bone remodeling. Here, we examine the effect of microcracks specifically on osteoblasts, which are bone-forming cells, by comparing cell responses on microcracked versus non-microcracked hydroxyapatit...

  17. 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

    marrow composition revealed a total absence of marrow adipocytes in HSD1(-/-) mice. Cells from Wt and HSD1(-/-) mice exhibited similar growth rates as well as similar levels of production of osteoblastic markers. The adipocyte-forming capacity of in vitro cultured bone marrow stromal cells and trabecular...

  18. Suppression of serum iron-binding capacity and bone marrow cellularity in pigs fed aflatoxin

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, R.B.; Clark, D.E.; Huff, W.E.; Kubena, L.F.; Corrier, D.E.; Phillips, I.D.

    1988-04-01

    Flavus-parasiticus species of the genus Aspergillus are recognized as the primary producers of aflatoxins B/sub 1/, B/sup 2/, G/sup 1/, and G/sup 2/, hereafter referred to as aflatoxin (AF). The effects of feeding AF-contaminated diets to growing and finishing pigs have been described with changes in clinical performance, serum biochemistry, histology, and hematology attributed to aflatoxicosis. However, most of these studies evaluated AF-induced changes for a single AF dosage at a given point in time. The present study was designed to characterize how various AF dosages influence bone marrow histology, hematology, prothrombin and activated thromboplastin times, serum amino acids, and serum iron binding capacity during aflatoxicosis in growing pigs.

  19. Suppression of serum iron-binding capacity and bone marrow cellularity in pigs fed aflatoxin

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, R.B.; Clark, D.E.; Huff, W.E.; Kubena, L.F.; Corrier, D.E. (USDA, College Station, TX (USA)); Phillips, T.D. (Texas A M Univ., College Station (USA))

    1988-05-01

    Flavus-parasiticus species of the genus Aspergillus are recognized as the primary producers of aflatoxins B{sub 1}, B{sub 2}, G{sub 1}, and G{sub 2}, hereafter referred to as aflatoxin (AF). The effects of feeding AF-contaminated diets to growing and finishing pigs have been described with changes in clinical performance, serum biochemistry, histology, and hematology attributed to aflatoxicosis. However, most of these studies evaluated AF-induced changes for a single AF dosage at a given point in time. The present study was designed to characterize how various AF dosages influence bone marrow histology, hematology, prothrombin and activated thromboplastin times, serum amino acids, and serum iron binding capacity during aflatoxicosis in growing pigs.

  20. Radiostrontium clearance and bone formation in response to simulated internal screw fixation

    International Nuclear Information System (INIS)

    Changes in radiostrontium clearance (SrC) and bone formation (tetracycline labeling) were observed in the femurs of skeletally mature dogs following the various operative steps involved in bone screw fixation. Drilling, but not periosteal stripping, produced a small but statistically significant increase in SrC and endosteal bone formation in the distal third of the bone. Strontium clearance values equivalent to those produced by drilling alone were recorded after screw fixation at low or high torque (5 versus 20 inch pounds), as well as by the insertion of loosely fitting stainless steel implants. Bone formation (equals the percentage tetracycline-labeled trabecular bone surfaces) was increased by 30% when SrC values exceeded 3.5 ml/100 g bone/min, and the relationship was linear when SrC values ranged between 1.0 and 7.0 ml/100 g bone/min. The changes in SrC and bone formation one-week after bone screw application are primarily those associated with a response to local trauma caused by drilling

  1. Bone formation in trabecular bone of thoracic and lumbar vertebral bodies as measured by tetracycline label evaluation

    International Nuclear Information System (INIS)

    Trabecular bone from thoracic and lumbar vertebral bodies of young adult beagles was evaluated for bone formation characteristics in eight beagles, using tetracycline pre-labeling. About 3 percent of the surface was continually-forming during a twelve day interval, while from 7 to 29 percent of the surface was forming bone intermittently over the twelve day span. Analysis of cross-sections provided a clearer picture of the results than did analysis of longitudinally-cut sections. There was no statistical difference in males and females or in oral vs. intravenous administration of tetracycline

  2. 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 L; Hauge, Ellen M; Rolighed, Lars; Bollerslev, Jens; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie

    2014-01-01

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

  3. 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...

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

    International Nuclear Information System (INIS)

    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)

  5. Short-term aluminum administration in the rat: reductions in bone formation without osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, W.G.

    1984-05-01

    Aluminum may be a pathogenic factor in dialysis-associated osteomalacia. To study the early effects of Al on bone, cortical bone growth was measured in pair-fed rats given Al and control rats over two consecutive intervals of 28 (period I) and 16 (period II) days, respectively, using tetracycline labeling of bone. Al (2 mg elemental Al per rat) was administered intraperitoneally for 5 days each week, except for the first week of study, when an incremental dose of Al was given. Control rats received saline vehicle only. For the entire 44-day study, bone and matrix formation were reduced from control values in rats given Al. Although bone and matrix formation remained at control levels during period I in rats given Al, both measurements decreased from control values during period II. During Al exposure, bone and matrix apposition at the periosteum were reduced from control levels in period II, but not in period I. Neither osteoid width nor mineralization front width increased from control values in rats given Al. These findings indicate that Al reduces bone and matrix formation early in the course of Al exposure and prior to the development of histologic osteomalacia. Rather than acting as an inhibitor of mineralization, the early effect of Al on bone is the suppression of matrix synthesis. Our results suggest that the state of low bone formation seen in dialysis-associated osteomalacia may be the consequence of a direct toxic effect of Al on the cellular activity of osteoblasts. 29 references, 3 tables.

  6. Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits

    Science.gov (United States)

    Li, Yunfeng; Li, Rui; Hu, Jing; Song, Donghui; Jiang, Xiaowen

    2016-01-01

    Introduction Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. Material and methods The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. Results It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. Conclusions The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID:27279839

  7. 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. PMID:27075029

  8. Low-intensity pulsed ultrasound prompts tissue-engineered bone formation after implantation surgery

    Institute of Scientific and Technical Information of China (English)

    Wang Juyong; Wang Juqiang; Asou Yoshinori; Paul Fu; Shen Huiliang; Chen Jiani; Sotome Shinichi

    2014-01-01

    Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts.Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds,enhanced production of bone marrow cells,and improved tissue-engineered bone formation.The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells (BMSCs).Methods BMSCs/β-tricalcium phosphate (β-TCP) composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound (LIPUS) treatment group and a control group.These implants were harvested at 5,10,25,and 50 days after implantation.The samples were then biomechanically tested and analyzed for alkaline phosphate (ALP) activity and osteocalcin (OCN) content and were also observed by light microscopy.Results The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group.Histomorphometric analysis revealed a greater degree of soft tissue repair,increased blood flow,better angiogenesis,and more extensive bone formation in the LIPUS groups than in the controls.No significant difference in the compressive strength was found between the two groups.Conclusion LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β3-TCP composites.

  9. 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

    2015-01-01

    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. PMID:25554598

  10. The use of computed tomography to quantitate bone formation after distraction epiphysiolysis in the rabbit

    International Nuclear Information System (INIS)

    A study of limb lengthening by distraction epiphysiolysis in the rabbit tibia is presented. For this purpose a special external distraction device was developed, which allowed 10 mm lengthening of the leg. Bone formation in the distraction zone was quantified by means of computed tomography. Cross-sectional scan planes at 1.5 mm separation revealed bone formation proceeding for several weeks after the end of the distraction period. A period of bone remodeling followed, resulting in the formation of a solid cortical structure, similar to the diaphysis, in the distraction zone. (orig.)

  11. Increased bone formation in a rabbit long-bone defect model after single local and single systemic application of erythropoietin.

    Science.gov (United States)

    Omlor, Georg W; Kleinschmidt, Kerstin; Gantz, Simone; Speicher, Anja; Guehring, Thorsten; Richter, Wiltrud

    2016-08-01

    Background and purpose - Delayed bone healing with non-union is a common problem. Further options to increase bone healing together with surgery are needed. We therefore evaluated a 1-dose single application of erythropoietin (EPO), applied either locally to the defect or systemically during surgery, in a critical-size rabbit long-bone defect. Material and methods - 19 New Zealand White rabbits received a 15-mm defect in the radius diaphysis. An absorbable gelatin sponge was soaked with saline (control group and systemic treatment group) or EPO (local treatment group) and implanted into the gap. The systemic treatment group received EPO subcutaneously. In vivo micro-CT analysis was performed 4, 8, and 12 weeks postoperatively. Vascularization was evaluated histologically. Results - Semiquantitative histomorphometric and radiological evaluation showed increased bone formation (2.3- to 2.5-fold) in both treatment groups after 12 weeks compared to the controls. Quantitative determination of bone volume and tissue volume showed superior bone healing after EPO treatment at all follow-up time points, with the highest values after 12 weeks in locally treated animals (3.0- to 3.4-fold). More vascularization was found in both EPO treatment groups. Interpretation - Initial single dosing with EPO was sufficient to increase bone healing substantially after 12 weeks of follow-up. Local application inside the defect was most effective, and it can be administered directly during surgery. Apart from effects on ossification, systemic and local EPO treatment leads to increased callus vascularization. PMID:27348783

  12. The Effect of Skeletal Unloading on Bone Formation: Role of IGF-I

    Science.gov (United States)

    Bikle, D. D.; Kostenuik, P.; Holton, E. M.; Halloran, B. P.

    1999-01-01

    The best documented change in bone during space flight is the near cessation of bone formation. Space flight leads to a decrease in osteoblast number and activity, likely the result of altered differentiation of osteoblast precursors. The net result of these space flight induced changes is weaker bone. To understand the mechanism for these changes poses a challenge. Space flight studies must overcome enormous technical problems, and are necessarily limited in size and frequency. Therefore, ground based models have been developed to evaluate the effects of skeletal unloading. The hindlimb elevation (tail suspension) model simulates space flight better than other models because it reproduces the fluid shifts seen in space travel, is reversible, and is well tolerated by the animals with minimal evidence of stress as indicated by continued weight gain and normal levels and circadian rhythms of corticosterone. This is the model we have used for our experiments. Skeletal unloading by the hindlimb elevation method simulates a number of features of space flight in that bone formation, mineralization, and maturation are inhibited, osteoblast number is decreased, serum and skeletal osteocalcin levels fall, the ash content of bone decreases, and bone strength diminishes. We and others have shown that when osteoblasts or osteoprogenitor cells from the bones of the unloaded limbs are cultured in vitro they proliferate and differentiate more slowly, suggesting that skeletal unloading causes a persistent change in cell function which can be assessed in vitro. In contrast to the unweighted bones of the hindlimbs, no significant change in bone mass or bone formation is observed in the humeri, mandible, and cervical vertebrae during hindlimb elevation. The lack of effect of hindlimb elevation on bones like the humeri, mandible, and cervical vertebrae which are not unloaded by this procedure suggests that local factors rather than systemic effects dominate the response of bone to

  13. Load bearing capacity of bone anchored fiber-reinforced composite device.

    Science.gov (United States)

    Ballo, Ahmed Mansour; Lassila, Lippo V; Vallittu, Pekka K; Närhi, Timo O

    2007-10-01

    The purpose of this study was to evaluate the push-out load-bearing capacity of threaded fiber-reinforced composite (FRC) devices for use as bone-anchored devices. The purpose was also to evaluate the possibility to use bioactive glass (BAG) granules on the experimental FRC devices in terms the mechanical behavior. Three experimental FRC devices (n = 15) were fabricated for the study: (a) threaded device with smooth surface; (b) threaded device with BAG granules (S53P4, Vivoxid Ltd, Turku, Finland) and supplementary retention grooves, and (c) unthreaded device with BAG granules. Threaded titanium devices were used as controls. The FRC devices were prepared from a light-polymerized dimethacrylate resin reinforced with preimpregnated unidirectional and bidirectional E-glass fibers (EverStick, StickTech Ltd, Turku, Finland). Experimental and control devices were embedded into dental plaster to simulate bone before the mechanical push-out test was carried out. ANOVA and Weibull analysis were used for the statistical evaluation. Threaded FRC devices had significantly higher push-out strength than the threaded titanium device (p < .001). The push-out forces exceeding 2,500 N were measured for threaded FRC devices with supplementary grooves and BAG coating. No thread failures were observed in any FRC devices. The unthreaded FRC devices with BAG lost 70% of glass particles during the test, while no BAG particles were lost from threaded FRC devices. It can be concluded that threaded FRC devices can withstand high push-out forces in the dental plaster without a risk of thread failure under physiological load. PMID:17558473

  14. The Effect of Heparan Sulfate Application on Bone Formation during Distraction Osteogenesis

    OpenAIRE

    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 re...

  15. TGF-βand BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

    Institute of Scientific and Technical Information of China (English)

    Mengrui Wu; Guiqian Chen; and Yi-Ping Li

    2016-01-01

    Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-βand BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-βand BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-βand BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.

  16. Heat and Radiofrequency Plasma Glow Discharge Pretreatment of a Titanium Alloy Promote Bone Formation and Osseointegration

    OpenAIRE

    MacDonald, Daniel E.; Rapuano, Bruce E.; Vyas, Parth; Lane, Joseph M.; Meyers, Kathleen; Wright, Timothy

    2013-01-01

    Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600°C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1 nM) or left unc...

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

    OpenAIRE

    Ali Murat Tatlı; Seyda Gunduz; Sema Sezgin Göksu; Deniz Arslan; Mukremin Uysal; Cumhur İbrahim Başsorgun; Hasan Şenol Coşkun

    2013-01-01

    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 ...

  18. 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.

  19. 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.

  20. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development

    OpenAIRE

    Ducy, Patricia; Starbuck, Michael; Priemel, Matthias; Shen, Jianhe; Pinero, Gerald; Geoffroy, Valerie; Amling, Michael; Karsenty, Gerard

    1999-01-01

    The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in C...

  1. 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

    canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone...

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

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Henriksen, Kim; Sørensen, Mette G;

    2005-01-01

    investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ovariectomy model withtwice daily oral dosing of NS3696 at 50 mg/kg for 6 weeks. We observed a 60% decrease in resorption (DPYR), increased tartrate-resistant acid phosphatase levels, and no effect on bone formation...

  3. 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...

  4. 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...

  5. Chondrocytes-Specific Expression of Osteoprotegerin Modulates Osteoclast Formation in Metaphyseal Bone

    OpenAIRE

    Baoli Wang; Hongting Jin; Bing Shu; Ranim R. Mira; Di Chen

    2015-01-01

    Bone marrow stromal cells/osteoblasts were originally thought to be the major player in regulating osteoclast differentiation through expressing RANKL/OPG cytokines. Recent studies have established that chondrocytes also express RANKL/OPG and support osteoclast formation. Till now, the in vivo function of chondrocyte-produced OPG in osteoclast formation and postnatal bone growth has not been directly investigated. In this study, chondrocyte-specific Opg transgenic mice were generated by using...

  6. [Recruitment of osteogenic cells to bone formation sites during development and fracture repair - German Version].

    Science.gov (United States)

    Böhm, A-M; Dirckx, N; Maes, C

    2016-04-01

    Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated. PMID:27003859

  7. In Vivo Ectopic Bone Formation by Devitalized Mineralized Stem Cell Carriers Produced Under Mineralizing Culture Condition

    OpenAIRE

    Chai, Yoke Chin; Geris, Liesbet; Bolander, Johanna; Pyka, Gregory; Van Bael, Simon; Luyten, Frank; Schrooten, Jan

    2014-01-01

    Abstract Functionalization of tissue engineering scaffolds with in vitro–generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem cells in vitro. However, the bone-forming capacity of these constructs (seeded with or without cells) is so far not apparent. In this study, we aimed at developing a mineralizing culture condition to biofunctionalize three-dimensional (3D) porous scaffolds with highly mineralized ECM in...

  8. Tissue-engineered bone formation using human bone marrow stromal cells and novel β-tricalcium phosphate

    International Nuclear Information System (INIS)

    In this study we investigated not only the cellular proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) on the novel β-tricalcium phosphate (β-TCP) scaffolds in vitro but also bone formation by ectopic implantation in athymic mice in vivo. The interconnected porous β-TCP scaffolds with pores of 300-500 μm in size were prepared by the polymeric sponge method. β-TCP scaffolds with the dimension of 3 mm x 3 mm x 3 mm were combined with hBMSCs, and incubated with (+) or without (-) osteogenic medium in vitro. Cell proliferation and osteogenic differentiation on the scaffolds were evaluated by scanning electron microscopy (SEM) observation, MTT assay, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content measurement. SEM observation showed that hBMSCs attached well on the scaffolds and proliferated rapidly. No significant difference in the MTT assay could be detected between the two groups, but the ALP activity and OCN content of scaffolds (+) were much higher than those of the scaffolds (-) (p < 0.05). These results indicated that the novel porous β-TCP scaffolds can support the proliferation and subsequent osteogenic differentiation of hBMSCs in vitro. After being cultured in vitro for 14 days, the scaffolds (+) and (-) were implanted into subcutaneous sites of athymic mice. In β-TCP scaffolds (+), woven bone formed after 4 weeks of implantation and osteogenesis progressed with time. Furthermore, tissue-engineered bone could be found at 8 weeks, and remodeled lamellar bone was also observed at 12 weeks. However, no bone formation could be found in β-TCP scaffolds (-) at each time point checked. The above findings illustrate that the novel porous β-TCP scaffolds developed in this work have prominent osteoconductive activity and the potential for applications in bone tissue engineering

  9. 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.

  10. Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    汤亭亭; 徐小良; 戴尅戎; 郁朝锋; 岳冰; 楼觉人

    2005-01-01

    Objective: To evaluate the osteogenic potential of bone morphogenetic protein (BMP)-2 gene transfected goat bone marrow-derived mesenchymal stem cells (MSCs). Methods: Goat bone marrow- derived MSCs were transfected by Adv-human bone morphogenetic protein (hBMP)-2 gene(Group 1), Adv-beta gal transfected MSCs (Group 2)and uninfected MSCs(Group 3). Western blot analysis, alkaline phosphatase staining, Von Kossa staining and transmission electron microscopy were adopted to determine the phenotype of MSCs. Then the cells were injected into thigh muscles of the nude mice. Radiographical and histological evaluations were performed at different intervals. Results: Only Adv-hBMP-2 transfected MSCs produced hBMP-2. These cells were positive for alkaline phosphatase staining at the 12th day and were positive for Von Kossa staining at the 16th day after gene transfer. Electron microscopic observation showed that there were more rough endoplasmic reticulum, mitochondria and lysosomes in Adv-hBMP-2 transfected MSCs compared to MSCs of other two groups. At the 3rd and 6th weeks after cell injection, ectopic bones were observed in muscles of nude mice of Group 1. Only fibrous tissue or a little bone was found in other two groups. Conclusions: BMP-2 gene transfected MSCs can differentiate into osteoblasts in vitro and induce bone formation in vivo.

  11. Sprouty2 regulates endochondral bone formation by modulation of RTK and BMP signaling.

    Science.gov (United States)

    Joo, Adriane; Long, Roger; Cheng, Zhiqiang; Alexander, Courtney; Chang, Wenhan; Klein, Ophir D

    2016-07-01

    Skeletal development is regulated by the coordinated activity of signaling molecules that are both produced locally by cartilage and bone cells and also circulate systemically. During embryonic development and postnatal bone remodeling, receptor tyrosine kinase (RTK) superfamily members play critical roles in the proliferation, survival, and differentiation of chondrocytes, osteoblasts, osteoclasts, and other bone cells. Recently, several molecules that regulate RTK signaling have been identified, including the four members of the Sprouty (Spry) family (Spry1-4). We report that Spry2 plays an important role in regulation of endochondral bone formation. Mice in which the Spry2 gene has been deleted have defective chondrogenesis and endochondral bone formation, with a postnatal decrease in skeletal size and trabecular bone mass. In these constitutive Spry2 mutants, both chondrocytes and osteoblasts undergo increased cell proliferation and impaired terminal differentiation. Tissue-specific Spry2 deletion by either osteoblast- (Col1-Cre) or chondrocyte- (Col2-Cre) specific drivers led to decreased relative bone mass, demonstrating the critical role of Spry2 in both cell types. Molecular analyses of signaling pathways in Spry2(-/-) mice revealed an unexpected upregulation of BMP signaling and decrease in RTK signaling. These results identify Spry2 as a critical regulator of endochondral bone formation that modulates signaling in both osteoblast and chondrocyte lineages. PMID:27130872

  12. The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation.

    Directory of Open Access Journals (Sweden)

    Erik Maronde

    Full Text Available BACKGROUND: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. METHODOLOGY/PRINCIPAL FINDINGS: We found that Per2(Brdm1 mutant mice as well as mice lacking Cry2(-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2(Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2(-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2(-/- mutants despite the simultaneous inactivation of Per2. CONCLUSIONS/SIGNIFICANCE: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters.

  13. 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

  14. 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; 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......-antagonistic properties, have increased energy expenditure and bone mass. Since these mice express ¿FosB in bone, fat and hypothalamus, we sought to determine 1) whether overexpression of ¿FosB 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 ¿FosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass...

  15. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    Science.gov (United States)

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID:26141839

  16. Osteoclast formation from mononuclear phagocytes : role of bone forming cells

    OpenAIRE

    Burger, E.H.; Meer, J.W.M. van der; Nijweide, P. J.

    1984-01-01

    In a previous study, using co-cultures of embryonic bone rudiments stripped of periosteum, and mononuclear phagocytes of various sources, we found that multinucleated mineral-resorbing osteoclasts developed in vitro from radiosensitive mouse bone marrow mononuclear phagocytes (BMMP). (Burger, E. H., J. W. M. van der Meer, J. S. van de Gevel, C. W. Thesingh, and R. van Furth, 1982, J. Exp. Med. 156:1604-1614). In the present study, this co-culture technique was used to analyze the influence of...

  17. 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)

    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 PTH1–34 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

  18. 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

  19. 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.

  20. 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.

  1. Forskolin enhances in vivo bone formation by human mesenchymal stromal cells.

    Science.gov (United States)

    Doorn, Joyce; Siddappa, Ramakrishnaiah; van Blitterswijk, Clemens A; de Boer, Jan

    2012-03-01

    Activation of the protein kinase A (PKA) pathway with dibutyryl cyclic adenosine monophosphate (db-cAMP) was recently shown to enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs) in vitro and bone formation in vivo. The major drawback of this compound is its inhibitory effect on proliferation of hMSCs. Therefore, we investigated whether fine-tuning of the dose and timing of PKA activation could enhance bone formation even further, with minimum effects on proliferation. To test this, we selected two different PKA activators (8-bromo-cAMP (8-br-cAMP) and forskolin) and compared their effects on proliferation and osteogenic differentiation with those of db-cAMP. We found that all three compounds induced alkaline phosphatase levels, bone-specific target genes, and secretion of insulin-like growth factor-1, although 8-br-cAMP induced adipogenic differentiation in long-term cultures and was thus considered unsuitable for further in vivo testing. All three compounds inhibited proliferation of hMSCs in a dose-dependent manner, with forskolin inhibiting proliferation most. The effect of forskolin on in vivo bone formation was tested by pretreating hMSCs before implantation, and we observed greater amounts of bone using forskolin than db-cAMP. Our data show forskolin to be a novel agent that can be used to increase bone formation and also suggests a role for PKA in the delicate balance between adipogenic and osteogenic differentiation. PMID:21942968

  2. 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

    defects, 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...... amount of bone marrow was increased 75% in the rhPDGF-BB-treated defect. The porosity of cortical lamella in the newly formed bone was 84% higher in the rhPDGF-BB-treated defects compared to the control. These results show that administration of a single dose of rhPDGF-BB stimulates bone formation in...

  3. Influence of interfacial properties and inhomogeneity on formation of microdamage in bone

    Science.gov (United States)

    Nakade, Rugved

    Microdamage accumulation at the nanoscopic level of bone affects the overall mechanical behavior of the bone. This makes it necessary to study the mechanisms through which microdamage accumulation can take place at the nanoscopic level. Experiments on bone's different hierarchy are difficult because of the small sizes of these hierarchical structures. Prevention of bone fractures is greatly enhanced with the help of predictive computational tools and hence used to evaluate the effects of microdamage in bone. There are two main types of microdamage that can form in the bone; linear cracks and diffuse damage. The bone nanostructure consists of mineral platelets embedded in soft protein called collagen and can be treated as a composite material. In this study, a two-dimensional probabilistic finite element model of the bone nanostructure was developed to evaluate the likely formation of the microdamage in the nanostructure due to changes in material properties of the nanostructure. The influence of the microdamage formation due to the collagen-mineral interface strength and also the effects of inhomogeneity were studied. To study interfacial strength effects, cohesive elements using bilinear traction separation laws were used to simulate the behavior of the interface (by way of interfacial debonding) between the collegen-mineral layers. Random field theory was used to assign spatially correlated random variables in order to assign inhomogeneous material properties to the bone. Correlation lengths were used to control the level of inhomogeneity in the model. The analysis showed that the type of microdamage was significantly influenced by the strength of the mineral-collagen interface. Probabilistic failure analyses indicated that strong interfaces resulted in limited interfacial debonding and narrow stress concentrations around an initial defect in the mineral-collagen composite, thereby suggesting that the likely location of failure was in same plane of the initial

  4. Low-Level Mechanical Vibrations can Reduce Bone Resorption and Enhance Bone Formation in the Growing Skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Xie,L.; Jacobsen, J.; Busa, B.; Donahue, L.; Miller, L.; Rubin, C.; Judex, S.

    2006-01-01

    Short durations of extremely small magnitude, high-frequency, mechanical stimuli can promote anabolic activity in the adult skeleton. Here, it is determined if such signals can influence trabecular and cortical formative and resorptive activity in the growing skeleton, if the newly formed bone is of high quality, and if the insertion of rest periods during the loading phase would enhance the efficacy of the mechanical regimen. Eight-week-old female BALB/cByJ mice were divided into four groups, baseline control (n = 8), age-matched control (n = 10), whole-body vibration (WBV) at 45 Hz (0.3 g) for 15 min day{sup -1} (n = 10), and WBV that were interrupted every second by 10 of rest (WBV-R, n = 10). In vivo strain gaging of two additional mice indicated that the mechanical signal induced strain oscillations of approximately 10 microstrain on the periosteal surface of the proximal tibia. After 3 weeks of WBV, applied for 15 min each day, osteoclastic activity in the trabecular metaphysis and epiphysis of the tibia was 33% and 31% lower (P < 0.05) than in age-matched controls. Bone formation rates (BFR{center_dot}BS{sup -1}) on the endocortical surface of the metaphysis were 30% greater (P < 0.05) in WBV than in age-matched control mice but trabecular and middiaphyseal BFR were not significantly altered. The insertion of rest periods (WBV-R) failed to potentiate the cellular effects. Three weeks of either WBV or WBV-R did not negatively influence body mass, bone length, or chemical bone matrix properties of the tibia. These data indicate that in the growing skeleton, short daily periods of extremely small, high-frequency mechanical signals can inhibit trabecular bone resorption, site specifically attenuate the declining levels of bone formation, and maintain a high level of matrix quality. If WBV prove to be efficacious in the growing human skeleton, they may be able to provide the basis for a non-pharmacological and safe means to increase peak bone mass and, ultimately

  5. 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

  6. A correlative imaging based methodology for accurate quantitative assessment of bone formation in additive manufactured implants.

    Science.gov (United States)

    Geng, Hua; Todd, Naomi M; Devlin-Mullin, Aine; Poologasundarampillai, Gowsihan; Kim, Taek Bo; Madi, Kamel; Cartmell, Sarah; Mitchell, Christopher A; Jones, Julian R; Lee, Peter D

    2016-06-01

    A correlative imaging methodology was developed to accurately quantify bone formation in the complex lattice structure of additive manufactured implants. Micro computed tomography (μCT) and histomorphometry were combined, integrating the best features from both, while demonstrating the limitations of each imaging modality. This semi-automatic methodology registered each modality using a coarse graining technique to speed the registration of 2D histology sections to high resolution 3D μCT datasets. Once registered, histomorphometric qualitative and quantitative bone descriptors were directly correlated to 3D quantitative bone descriptors, such as bone ingrowth and bone contact. The correlative imaging allowed the significant volumetric shrinkage of histology sections to be quantified for the first time (~15 %). This technique demonstrated the importance of location of the histological section, demonstrating that up to a 30 % offset can be introduced. The results were used to quantitatively demonstrate the effectiveness of 3D printed titanium lattice implants. PMID:27153828

  7. The effects of n-3 long-chain polyunsaturated fatty acids on bone formation and growth factors in adolescent boys

    DEFF Research Database (Denmark)

    Damsgaard, C. T.; Mølgaard, C.; Gyldenløve, S. N.;

    2012-01-01

    NTRODUCTION: Animal studies indicate that n-3 long-chain polyunsaturated fatty acids (LCPUFAs) increase bone formation. To our knowledge, no studies have examined this in growing humans. This study investigated whether bone mass and markers of bone formation and growth were (i) associated with......-1 (IGF-1) during intervention (β = 0.24, P = 0.03, n = 78). DISCUSSION: DHA status and fish oil supplementation were not associated with bone mass or markers of bone formation in adolescent boys, but IGF-1 increased with increasing DHA status....

  8. 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.

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

    Science.gov (United States)

    Tatlı, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Coşkun, Hasan Şenol

    2013-01-01

    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. PMID:23956898

  10. Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells.

    Science.gov (United States)

    Schulze, Jochen; Bickert, Thomas; Beil, F Timo; Zaiss, Mario M; Albers, Joachim; Wintges, Kristofer; Streichert, Thomas; Klaetschke, Kristin; Keller, Johannes; Hissnauer, Tim-Nicolas; Spiro, Alexander S; Gessner, Andre; Schett, Georg; Amling, Michael; McKenzie, Andrew N J; Horst, Andrea Kristina; Schinke, Thorsten

    2011-04-01

    Since the hematopoetic system is located within the bone marrow, it is not surprising that recent evidence has demonstrated the existence of molecular interactions between bone and immune cells. While interleukin 1 (IL-1) and IL-18, two cytokines of the IL-1 family, have been shown to regulate differentiation and activity of bone cells, the role of IL-33, another IL-1 family member, has not been addressed yet. Since we observed that the expression of IL-33 increases during osteoblast differentiation, we analyzed its possible influence on bone formation and observed that IL-33 did not affect matrix mineralization but enhanced the expression of Tnfsf11, the gene encoding RANKL. This finding led us to analyze the skeletal phenotype of Il1rl1-deficient mice, which lack the IL-33 receptor ST2. Unexpectedly, these mice displayed normal bone formation but increased bone resorption, thereby resulting in low trabecular bone mass. Since this finding suggested a negative influence of IL-33 on osteoclastogenesis, we next analyzed osteoclast differentiation from bone marrow precursor cells and observed that IL-33 completely abolished the generation of TRACP(+) multinucleated osteoclasts, even in the presence of RANKL and macrophage colony-stimulating factor (M-CSF). Although our molecular studies revealed that IL-33 treatment of bone marrow cells caused a shift toward other hematopoetic lineages, we further observed a direct negative influence of IL-33 on the osteoclastogenic differentiation of RAW264.7 macrophages, where IL-33 repressed the expression of Nfatc1, which encodes one of the key transciption factors of osteoclast differentiation. Taken together, these findings have uncovered a previously unknown function of IL-33 as an inhibitor of bone resorption. PMID:20939024

  11. Thrombospondin 1 promotes synaptic formation in bone marrow-derived neuron-like cells★

    OpenAIRE

    Huang, Yun; Lu, Mingnan; Guo, Weitao; Zeng, Rong; Wang, Bin; Wang, Huaibo

    2013-01-01

    In this study, a combination of growth factors was used to induce bone marrow mesenchymal stem cells differentiation into neuron-like cells, in a broader attempt to observe the role of thrombospondin 1 in synapse formation. Results showed that there was no significant difference in the differentiation rate of neuron-like cells between bone marrow mesenchymal stem cells with thrombospondin induction and those without. However, the cell shape was more complex and the neurites were dendritic, wi...

  12. Kartogenin induces cartilage-like tissue formation in tendon–bone junction

    OpenAIRE

    Zhang, Jianying; Wang, James H-C.

    2014-01-01

    Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells...

  13. 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.

  14. 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; Hauge, Ellen Margrethe; Bollerslev, Jens; Amling, Michael; Barvencik, Florian; Delaissé, Jean-Marie

    2011-01-01

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

  15. 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 ...

  16. 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. PMID:26031934

  17. 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.

  18. 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.

  19. 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 form...

  20. Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II

    OpenAIRE

    Kollmann, Katrin; Pestka, Jan Malte; Kühn, Sonja Christin; Schöne, Elisabeth; Schweizer, Michaela; Karkmann, Kathrin; Otomo, Takanobu; Catala-Lehnen, Philip; Failla, Antonio Virgilio; Marshall, Robert Percy; Krause, Matthias; Santer, Rene; Amling, Michael; Braulke, Thomas; Schinke, Thorsten

    2013-01-01

    Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency...

  1. Mechanical microenvironments and protein expression associated with formation of different skeletal tissues during bone healing.

    Science.gov (United States)

    Miller, Gregory J; Gerstenfeld, Louis C; Morgan, Elise F

    2015-11-01

    Uncovering the mechanisms of the sensitivity of bone healing to mechanical factors is critical for understanding the basic biology and mechanobiology of the skeleton, as well as for enhancing clinical treatment of bone injuries. This study refined an experimental method of measuring the strain microenvironment at the site of a bone injury during bone healing. This method used a rat model in which a well-controlled bending motion was applied to an osteotomy to induce the formation of pseudarthrosis that is composed of a range of skeletal tissues, including woven bone, cartilage, fibrocartilage, fibrous tissue, and clot tissue. The goal of this study was to identify both the features of the strain microenvironment associated with formation of these different tissues and the expression of proteins frequently implicated in sensing and transducing mechanical cues. By pairing the strain measurements with histological analyses that identified the regions in which each tissue type formed, we found that formation of the different tissue types occurs in distinct strain microenvironments and that the type of tissue formed is correlated most strongly to the local magnitudes of extensional and shear strains. Weaker correlations were found for dilatation. Immunohistochemical analyses of focal adhesion kinase and rho family proteins RhoA and CDC42 revealed differences within the cartilaginous tissues in the calluses from the pseudarthrosis model as compared to fracture calluses undergoing normal endochondral bone repair. These findings suggest the involvement of these proteins in the way by which mechanical stimuli modulate the process of cartilage formation during bone healing. PMID:25822264

  2. Laser Microablative Tunnel Formation to Initiate Alveolar Bone Regeneration. Pilot ex vivo Study

    Directory of Open Access Journals (Sweden)

    Karabut М.М.

    2013-12-01

    Full Text Available In recent years there has been demonstrated the ability of Erbium (Er laser to cause effective ablation of bone tissue with minimum collateral damage. Non-surgical treatment of periodontitis using Er laser improves probing depth and clinical attachment level. However, periodontal anti-inflammatory therapy should not be limited to these parameters, but also should initiate tissue regeneration including bone tissue damaged by the disease. The aim of the investigation was to evaluate feasibility and characterize the process of laser microablative tunnel formation in gingiva and alveolar bone using a pulse-periodic, single mode Er laser, and determine laser parameters providing appropriate size of the tunnel and coagulation zone needed to initiate healing and regeneration of the alveolar bone. Materials and Methods. Ex vivo pig jaw was used as a model for the study. To create a through-gingiva microperformation of the alveolar bone, we used a laboratory prototype of Er laser and delivery system Alta PE-AT (Dental Photonics, Inc.. Results. We performed a microperforation of a 1 mm thick gingiva and created a microcrater (tunnel in the underlying bone using a single pulse with energy 5, 10 and 30 mJ. The laser tunnel characteristics in the gingiva, bone and dentine were characterized as a function of laser irradiation parameters. Optical microscopy and histology examination did not reveal carbonization or significant collateral damage of the bone tissue. Conclusion. Using a laboratory prototype of Alta PE-AT Er laser we demonstrated feasibility of through gingiva laser microperforation of alveolar bone that can serve as the first step towards further study of healing and initiation of the alveolar bone regeneration.

  3. AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass

    OpenAIRE

    Shah, M; Kola, B; Bataveljic, A.; Arnett, T. R.; Viollet, B.; Saxon, L.; Korbonits, M.; C. Chenu

    2010-01-01

    Adenosine 5′-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cult...

  4. 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

  5. Thrombospondin 1 promotes synaptic formation in bone marrow-derived neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Yun Huang; Mingnan Lu; Weitao Guo; Rong Zeng; Bin Wang; Huaibo Wang

    2013-01-01

    In this study, a combination of growth factors was used to induce bone marrow mesenchymal stem cells differentiation into neuron-like cells, in a broader attempt to observe the role of thrombospondin 1 in synapse formation. Results showed that there was no significant difference in the differentiation rate of neuron-like cells between bone marrow mesenchymal stem cells with thrombospondin induction and those without. However, the cell shape was more complex and the neurites were dendritic, with unipolar, bipolar or multipolar morphologies, after induction with thrombospondin 1. The induced cells were similar in morphology to normal neurites. Immunohistochemical staining showed that the number of positive cells for postsynaptic density protein 95 and synaptophysin 1 protein was significantly increased after induction with thrombospondin 1. These findings indicate that thrombospondin 1 promotes synapse formation in neuron-like cells that are differentiated from bone marrow mesenchymal stem cells.

  6. Theory of SEI Formation in Rechargeable Batteries: Capacity Fade, Accelerated Aging and Lifetime Prediction

    OpenAIRE

    Pinson, Matthew B.; Bazant, Martin Z.

    2012-01-01

    Cycle life is critically important in applications of rechargeable batteries, but lifetime prediction is mostly based on empirical trends, rather than mathematical models. In practical lithium-ion batteries, capacity fade occurs over thousands of cycles, limited by slow electrochemical processes, such as the formation of a solid-electrolyte interphase (SEI) in the negative electrode, which compete with reversible lithium intercalation. Focusing on SEI growth as the canonical degradation mecha...

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

    OpenAIRE

    Mohammad Kargar; Rouhi Afkari; Sadegh Ghorbani-Dalini

    2013-01-01

    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 tota...

  8. 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. PMID:23988277

  9. Chondrocytes-Specific Expression of Osteoprotegerin Modulates Osteoclast Formation in Metaphyseal Bone.

    Science.gov (United States)

    Wang, Baoli; Jin, Hongting; Shu, Bing; Mira, Ranim R; Chen, Di

    2015-01-01

    Bone marrow stromal cells/osteoblasts were originally thought to be the major player in regulating osteoclast differentiation through expressing RANKL/OPG cytokines. Recent studies have established that chondrocytes also express RANKL/OPG and support osteoclast formation. Till now, the in vivo function of chondrocyte-produced OPG in osteoclast formation and postnatal bone growth has not been directly investigated. In this study, chondrocyte-specific Opg transgenic mice were generated by using type II collagen promoter. The Col2-Opg transgenic mice showed delayed formation of secondary ossification center and localized increase of bone mass in proximal metaphysis of tibiae. TRAP staining showed that osteoclast numbers were reduced in both secondary ossification center and proximal metaphysis. This finding was further confirmed by in vitro chondrocyte/spleen cell co-culture assay. In contrast, the mineral apposition rates were not changed in Col2-Opg transgenic mice. TUNEL staining revealed more apoptotic hypertrophic chondrocytes in the growth plate of Col2-Opg mice. Flow cytometry analysis showed fewer RANK-expressing cells in the marrow of Col2a1-Opg mice, suggesting the role of OPG in blocking the differentiation of early mesenchymal progenitors into RANK-expressing pre-osteoclasts. Our results demonstrated that OPG expression in chondrocyte increases bone mass in the proximal metaphysis of tibiae through negative regulation of osteoclast formation. PMID:26329493

  10. cAMP/PKA Signaling Inhibits Osteogenic Differentiation and Bone Formation in Rodent Models

    NARCIS (Netherlands)

    Siddappa, Ramakrishnaiah; Mulder, Winfried; Steeghs, Ilse; Klundert, van de Christine; Fernandes, Hugo; Liu, Jun; Arends, Roel; Blitterswijk, van Clemens; Boer, de Jan

    2009-01-01

    We previously demonstrated that cAMP-mediated protein kinase A (PKA) activation induces in vitro osteogenesis and in vivo bone formation by human mesenchymal stem cells (hMSCs). To analyze the species-specific response of this phenomenon and to translate our findings into a clinical trial, suitable

  11. Forskolin enhances in vivo bone formation by human mesenchymal stromal cells

    NARCIS (Netherlands)

    Doorn, J.; Siddappa, R.; Blitterswijk, van C.A.; Boer, de J.

    2012-01-01

    Activation of the protein kinase A (PKA) pathway with dibutyryl cyclic adenosine monophosphate (db-cAMP) was recently shown to enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs) in vitro and bone formation in vivo. The major drawback of this compound is its inhibitory effe

  12. Induction of DNA-strand breaks after X-irradiation in murine bone cells of various differentiation capacities

    Science.gov (United States)

    Lau, Patrick; Hellweg, Christine E.; Kirchner, Simone; Baumstark-Khan, Christa

    During longterm space missions, astronauts suffer from the loss of minerals especially from weightbearing bones due to prolonged sojourn under microgravity. In addition to weightlessness, exposure to cosmic ionization radiation is another space related factor endangering health and productivity of astronauts. In order to elucidate changes in bone cell metabolism induced by ionizing radiation, ground-based bone cell models have been developed. The differentiation level of the bone cells may influence their radiation sensitivity. Therefore, our cell model comprises a collection of immortalized murine pre-osteoblast, osteoblast and osteocyte cell lines representing discrete stages of differentiation: the subclones 4 and 24 of the osteoblast cell line MC3T3-E1, the osteoblast cell line OCT-1 and the osteocyte cell line MLO-Y4 display varying potential to produce mineralized bone matrix upon incubation with ascorbic acid and β-glycerophosphate (osteogenic medium). The MLO-Y4 cells showed the highest and subclone 24 the lowest proliferation rate. The most intense von Kossa reaction after culture in osteogenic medium was observed in subclone 4, indicating mineralized bone matrix. The bone cell markers alkaline phosphatase and osteocalcin were determined to further characterize the differentiation stage. All cell lines expressed osteocalcin, as determined by reverse transcriptase polymerase chain reaction. The activity of alkaline phosphatase was highest in the cell line OCT-1 and very low in MLO-Y4 and S4. The peculiarity of the markers suggests a characterization of OCT-1 and S24 as preosteoblast, S4 as (mature) osteoblast, and MLO-Y4 as osteocyte. Survival after exposure to X-rays was determined using the colony forming ability test. The resulting dose-effect relationships revealed normal radiation sensitivity (compared to human fibroblasts). Cell clone specific variations (subclones 4 and 24) in the radiation sensitivity may be due to the differentiation level. The

  13. 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

  14. Implantation of a polycaprolactone scaffold with subchondral bone anchoring ameliorates nodules formation and other tissue alterations

    OpenAIRE

    Vikingsson, Line; Sancho-Tello, Mar??a; Ruiz-Saur??, Amparo; Martinez-Diaz, Santos; G??mez-Tejedor, Jos?? Antonio; Gallego Ferrer, Gloria; Carda, Carmen; Monllau Garc??a, Juan Carlos; G??mez Ribelles, Jos?? Luis

    2016-01-01

    PURPOSE: Articular cartilage has limited repair capacity. Two different implant devices for articular cartilage regeneration were tested in vivo in a sheep model to evaluate the effect of subchondral bone anchoring for tissue repair. METHODS: The implants were placed with press-fit technique in a cartilage defect after microfracture surgery in the femoral condyle of the knee joint of the sheep and histologic and mechanical evaluation was done 4.5 months later. The first group consisted of a b...

  15. Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin

    Science.gov (United States)

    Ishijima, Muneaki; Rittling, Susan R.; Yamashita, Teruhito; Tsuji, Kunikazu; Kurosawa, Hisashi; Nifuji, Akira; Denhardt, David T.; Noda, Masaki

    2001-01-01

    Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN−/− mice using a tail suspension model. In contrast to the tail suspension–induced bone loss in wild-type mice, OPN−/− mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN−/− mice. Analysis of the mechanisms of OPN deficiency–dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN−/− mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN−/− mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts. PMID:11157060

  16. 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

  17. A myostatin and activin decoy receptor enhances bone formation in mice.

    Science.gov (United States)

    Bialek, P; Parkington, J; Li, X; Gavin, D; Wallace, C; Zhang, J; Root, A; Yan, G; Warner, L; Seeherman, H J; Yaworsky, P J

    2014-03-01

    Myostatin is a member of the bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty. PMID:24333131

  18. Efficacy of Intraperitoneal Administration of PEGylated NELL-1 for Bone Formation

    Science.gov (United States)

    Tanjaya, Justine; Zhang, Yulong; Lee, Soonchul; Shi, Jiayu; Chen, Eric; Ang, Pia; Zhang, Xinli; Tetradis, Sotirios; Ting, Kang; Wu, Benjamin; Soo, Chia; Kwak, Jin Hee

    2016-01-01

    Abstract Systemically delivered NEL-like molecule-1 (NELL-1), a potent pro-osteogenic protein, promotes bone formation in healthy and osteoporotic mouse models. PEGylation of NELL-1 (NELL-PEG) increases the half-life of the protein in a mouse model without compromising its osteogenic potential, thereby improving its pharmacokinetics upon systemic delivery. This study consists of a twofold approach: a biodistribution test and an in vivo osteogenic potential test. The biodistribution test compared two commonly used administration methods for drug delivery other than intravenous—intraperitoneal (IP) and subcutaneous (SC)—to examine NELL-PEG biodistribution in mice. Compared to a single-dose SC injection (1.25 mg/kg), a single-dose IP administration yielded a higher protein uptake in the targeted bone sites. When the IP injection dose was doubled to 2.5 mg/kg, the protein remained in the femurs, tibias, and vertebrae for up to 72 h. Next, based on the results of the biodistribution study, IP administration was selected to further investigate the in vivo osteogenic effects of weekly NELL-PEG injection (q7d). In vivo, the IP administered NELL-PEG group showed significantly greater bone mineral density, bone volume fraction, and trabecular bone formation in the targeted bone sites compared to the phosphate-buffered saline control. In summary, weekly NELL-PEG injection via IP administration successfully enhanced the overall bone quality. These findings demonstrate that systemic delivery of NELL-PEG via IP administration may serve as an effective osteogenic therapy for preventing and treating osteoporosis. PMID:27354930

  19. Pyk2 regulates megakaryocyte-induced increases in osteoblast number and bone formation.

    Science.gov (United States)

    Cheng, Ying-Hua; Hooker, R Adam; Nguyen, Khanh; Gerard-O'Riley, Rita; Waning, David L; Chitteti, Brahmananda R; Meijome, Tomas E; Chua, Hui Lin; Plett, Artur P; Orschell, Christie M; Srour, Edward F; Mayo, Lindsey D; Pavalko, Fredrick M; Bruzzaniti, Angela; Kacena, Melissa A

    2013-06-01

    Preclinical and clinical evidence from megakaryocyte (MK)-related diseases suggests that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We, therefore, examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 levels in OBs were significantly enhanced primarily because of increased Pyk2 gene transcription. Additionally, p53 and Mdm2 were both decreased in OBs upon MK stimulation, which would be permissive of cell cycle entry. We then demonstrated that OB number was markedly reduced when Pyk2-/- OBs, as opposed to wild-type (WT) OBs, were co-cultured with MKs. We also determined that MKs inhibit OB differentiation in the presence and absence of Pyk2 expression. Finally, given that MK-replete spleen cells from GATA-1-deficient mice can robustly stimulate OB proliferation and bone formation in WT mice, we adoptively transferred spleen cells from these mice into Pyk2-/- recipient mice. Importantly, GATA-1-deficient spleen cells failed to stimulate an increase in bone formation in Pyk2-/- mice, suggesting in vivo the important role of Pyk2 in the MK-induced increase in bone volume. Further understanding of the signaling pathways involved in the MK-mediated enhancement of OB number and bone formation will facilitate the development of novel anabolic therapies to treat bone loss diseases. PMID:23362087

  20. 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.

  1. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts.

    Science.gov (United States)

    Keller, Johannes; Catala-Lehnen, Philip; Huebner, Antje K; Jeschke, Anke; Heckt, Timo; Lueth, Anja; Krause, Matthias; Koehne, Till; Albers, Joachim; Schulze, Jochen; Schilling, Sarah; Haberland, Michael; Denninger, Hannah; Neven, Mona; Hermans-Borgmeyer, Irm; Streichert, Thomas; Breer, Stefan; Barvencik, Florian; Levkau, Bodo; Rathkolb, Birgit; Wolf, Eckhard; Calzada-Wack, Julia; Neff, Frauke; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabĕ; Klutmann, Susanne; Tsourdi, Elena; Hofbauer, Lorenz C; Kleuser, Burkhard; Chun, Jerold; Schinke, Thorsten; Amling, Michael

    2014-01-01

    The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P3. Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P3-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts. PMID:25333900

  2. Radiographic evaluation and unusual bone formations in different genetic patterns in synpolydactyly

    International Nuclear Information System (INIS)

    To compare the radiological findings of heterozygous and homozygous subjects with synpolydactyly (SPD) and to discuss their unusual bone formations. Families with hand and foot SPD were examined. Genetic analysis was performed with blood samples and the pedigree was constructed. The affected individuals, especially those with distinctive phenotypic features, were invited to our orthopaedics clinic for further diagnostic studies. All participants underwent detailed clinical and X-ray examinations. Of the invited patients, 16 (five female and 11 male; age range 4-37 years, mean age 10.75 years) were included in our study, and hand and foot radiographs were obtained. All subjects had bilateral hand radiographs (32 hands), and 14 had bilateral foot radiographs (28 feet). Genetic analysis revealed 12 heterozygote (75%) and four (25%) homozygote phenotypes. Among patients enrolled into the study nine (three homozygotes, six heterozygotes) had SPD of both hands and feet bilaterally (tetrasynpolydactyly). Six unusual bone formations were observed in the hands and feet: delta phalanx, delta metacarpal/metatarsal, kissing delta phalanx, true double epiphysis, pseudoepiphysis and cone-shaped epiphysis. There were major differences in radiological and clinical manifestations of homozygote and heterozygote phenotypes. The homozygous SPD presented with very distinctive unusual bone formations. The existence and variety of unusual bones may indicate the severity of penetrance and expressivity of SPD. (orig.)

  3. Teriparatide Increases Bone Formation and Bone Mineral Density in Adult Women With Anorexia Nervosa

    Science.gov (United States)

    Wang, Irene S.; Miller, Karen K.; Herzog, David B.; Misra, Madhusmita; Lee, Hang; Finkelstein, Joel S.; Bouxsein, Mary L.; Klibanski, Anne

    2014-01-01

    Context: Anorexia nervosa (AN), a prevalent psychiatric disorder predominantly affecting women, is characterized by self-induced starvation and low body weight. Increased clinical fractures are common, and most women have low bone mineral density (BMD). Previously investigated treatments have led to no or modest increases in BMD in AN. Objective: Our objective was to investigate the effect of teriparatide (TPT; human PTH[1–34]), an anabolic agent, on low bone mass in women with AN. Design, Setting, and Patients: This randomized, placebo-controlled trial at a clinical research center included 21 women with AN: 10 (mean age ± SEM, 47 ± 2.7 years) treated with TPT and 11 (47.1 ± 2.3 years) treated with placebo. Interventions: TPT (20 μg SC) or placebo was administered for 6 months. Main Outcome Measures: Our primary outcome measure was change in BMD of the spine and hip by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in serum N-terminal propeptide of type 1 procollagen (P1NP), C-terminal collagen cross-links, sclerostin, and IGF-1 levels. Results: At 6 months, spine BMD increased significantly more with TPT (posteroanterior spine, 6.0% ± 1.4%; lateral spine, 10.5% ± 2.5%) compared with placebo (posteroanterior spine, 0.2% ± 0.7%, P < .01; lateral spine, −0.6% ± 1.0%; P < .01). The results remained significant after controlling for baseline body mass index, P1NP, and IGF-1. Changes in femoral neck (P = .4) and total hip (P = 0.8) BMD were comparable in both groups, as were changes in weight. Serum P1NP levels increased after 3 months of TPT treatment and remained at this higher level at 6 months, whereas P1NP levels were unchanged in the placebo group (P = .02). TPT was well-tolerated by all subjects. Conclusions: This study demonstrates that TPT administration increases spine BMD substantially after only 6 months of therapy in women with AN. PMID:24456286

  4. Effects of magnetic resonance imaging (MRI) on the formation of mouse dentin and bone

    International Nuclear Information System (INIS)

    The effects of magnetic resonance imaging (MRI) on dentin and bone formation in mice were examined using standard autoradiographic and liquid scintillation procedures. It was observed that exposure to a standard 23.2 min clinical multislice MRI (0.15T) procedure caused a significant increase in the synthesis of the collagenous matrix of dentin in the incisors of mice. There were no significant effects on alveolar and tibial bone matrix synthesis. These results suggest that the magnetic fields associated with MRI can affect the activity of cells and/or tissues that are involved in rapid synthetic activity

  5. Zygomatico-coronoid ankylosis secondary to heterotopic bone formation: Combined treatment by surgery and radiation therapy

    International Nuclear Information System (INIS)

    Zygomatico-coronoid ankylosis is a rare, extra-articular form of ankylosis of the jaws. An unusual case is presented in which true bony zygomatico-coronoid ankylosis was produced by a mass of heterotopic bone. Surgical treatment consisted of an oblique ostectomy across the mandibular ascending ramus, with interposition of Silastic sheeting to form a pseudarthrosis. Since surgery is often the stimulus for this condition, 2000 rads were delivered to the surgical site postoperatively in order to inhibit recurrent heterotopic bone formation. The rationale and indications for this form of treatment are discussed. (orig.)

  6. Assessment of bone formation and bone resorption in osteoporosis: a comparison between tetracycline-based iliac histomorphometry and whole body 85Sr kinetics

    International Nuclear Information System (INIS)

    Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption

  7. [Impact of high-technology teaching systems on the formation of gymnasia pupils' adaptive capacities].

    Science.gov (United States)

    Sosnina, E V; Setko, A G

    2009-01-01

    The paper presents the results of studying the adaptive capacities in first-, fourth-, and fifth-form gymnasia pupils taught by the system developed by L. V. Zankov (Group 1) and M. Montessori (Group 2), by evaluating the functional status of the cardiovascular and central nervous systems and determining the level of biological adaptation. The findings are suggestive of the better adaptation and functional status of the central nervous and cardiovascular systems in the gymnasia pupils taught by the educational-and-developing program worked out by L. V. Zankov, which is likely to be explained by the training effect of functional capacities and by the formation of a long-acting effect that is shown in the better adaptation values on transition to the middle link of education. PMID:19802950

  8. Theory of SEI Formation in Rechargeable Batteries: Capacity Fade, Accelerated Aging and Lifetime Prediction

    CERN Document Server

    Pinson, Matthew B

    2012-01-01

    Cycle life is critically important in applications of rechargeable batteries, but lifetime prediction is mostly based on empirical trends, rather than mathematical models. In practical lithium-ion batteries, capacity fade occurs over thousands of cycles, limited by slow electrochemical processes, such as the formation of a solid-electrolyte interphase (SEI) in the negative electrode, which compete with reversible lithium intercalation. Focusing on SEI growth as the canonical degradation mechanism, we show that a simple single-particle model can accurately explain experimentally observed capacity fade in commercial cells with graphite anodes, and predict future fade based on limited accelerated aging data for short times and elevated temperatures. The theory is extended to porous electrodes, predicting that SEI growth is essentially homogeneous throughout the electrode, even at high rates. The lifetime distribution for a sample of batteries is found to be consistent with Gaussian statistics, as predicted by th...

  9. New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model

    Science.gov (United States)

    Kurniawati, Tri; Siregar, Nurjati Chairani; Syahrurachman, Agus; Dilogo, Ismail Hadisubroto; Iskandriati, Diah; Fitri, Arni Diana

    2016-01-01

    Study Design Preliminary experimental study using a rabbit spondylitis model. Purpose To observe the ossification in a micro-environment containing live Mycobacterium tuberculosis transplanted with bone marrow stromal cells (BMSCs) in rabbits. Overview of Literature BMSCs differentiate to osteoblasts and then osteocytes during ossification. Mycobacterium tuberculosis does not affect BMSC growth in vitro. Methods Six rabbits were divided into two groups of three rabbits. One group was positive for spondylitis tuberculosis by culture, polymerase chain reaction (PCR), and histopathologically. The other group was positive by PCR and histopathologically. Both groups were treated using BMSC transplantation and anti-tuberculosis drugs. After 6 weeks, ossification was evaluated by enumerating the number of osteoblasts, osteocytes, and lesion level of calcium. Results Mean number of osteoblasts was 207.00±31.00 in the first group and 220.33±73.46 in the second group. Mean number of intra-lesions osteocytes was in the first and second group was 18.33±30.04 and 31.00±26.87, respectively. Mean calcium level in the first group and second group was 2.94%±0.89% and 2.51%±0.13%, respectively. Total ossification score in the first and second group was 31.00 and 25.67, respectively. Conclusions Mycobacterium tuberculosis provides support for new bone formation by stimulating intra-lesion calcium metabolism. The microscopic environment containing live Mycobacterium tuberculosis enhances ossification. PMID:26949451

  10. Bone

    International Nuclear Information System (INIS)

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

  11. Fast and reliable determination of antioxidant capacity based on the formation of gold nanoparticles

    International Nuclear Information System (INIS)

    We demonstrate that the formation of gold nanoparticles (AuNPs) can be exploited in a well-defined and reliable electron-transfer assay for antioxidant capacity (AOxC). The AOxC of a sample usually is due to the presence of polyphenols, and a good correlation exists between the production of AuNPs and the concentration of polyphenols. The results obtained by this method correlate well with the established AOxC assays (FRAP and FC; p < 0.05). HPLC analysis revealed that the AOxC is driven by the overall quantitative levels of polyphenolic antioxidants. UV characterization and TEM confirm the formation of stabilized AuNPs of well-defined size (all <20 nm). This protocol represents a reliable yet inexpensive and fast approach compared to other methods to determine AOxC. (author)

  12. 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.

  13. Phosphate Interacts With PTHrP to Regulate Endochondral Bone Formation

    OpenAIRE

    Liu, Eva S.; Zalutskaya, Alena; Chae, Byongsoo Timothy; Zhu, Eric D.; Gori, Francesca; Demay, Marie B.

    2014-01-01

    Phosphate and parathyroid hormone related peptide (PTHrP) are required for normal growth plate maturation. Hypophosphatemia impairs hypertrophic chondrocyte apoptosis leading to rachitic expansion of the growth plate; however, the effect of phosphate restriction on chondrocyte differentiation during endochondral bone formation has not been examined. Investigations were, therefore, undertaken to address whether phosphate restriction alters the maturation of embryonic d15.5 murine metatarsal el...

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

    International Nuclear Information System (INIS)

    Highlights: • LiCoO2 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 LiCoO2 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 LiCoO2 (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 LiCoO2 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 LiCoO2 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

  15. Effect of mixed compounds on methane hydrate formation and dissociation rates and storage capacity

    Energy Technology Data Exchange (ETDEWEB)

    Ganji, H. [Department of Engineering and Development, Research Institute of Petroleum Industry, Tehran (Iran); Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, Tehran (Iran); Manteghian, M. [Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, Tehran (Iran); Rahimi Mofrad, H. [Department of Engineering and Development, Research Institute of Petroleum Industry, Tehran (Iran)

    2007-09-15

    To use gas hydrates for storage and transport of gas, the hydrate should be reasonably stable. Surfactants were found to increase the hydrate formation rate and storage capacity. On the other hand, they accelerate its decomposition rate. This study is concerned with methods of decreasing the dissociation rate of methane hydrate formed in the presence of sodium dodecyl sulfate (SDS). Using SDS solution with concentration of 500 ppm, the hydrate formation rate increased by the factor grater than 35 and the storage capacity was doubled. Below the ice point however, the stability of hydrate decreased effectively. While after 10 h 2.3 mol% of methane hydrate in pure water was dissociated at 268.2 K, the dissociation percentage was 9.7 wt.% for the hydrate formed in the SDS solution. By addition of a minor amount of xanthan or starch (so as to reach a concentration of 100-300 ppm in the solution) the dissociation rate of the methane hydrate was decreased effectively. (author)

  16. Short-term aluminum administration in the rat. Effects on bone formation and relationship to renal osteomalacia.

    OpenAIRE

    Goodman, W G; Gilligan, J; Horst, R.

    1984-01-01

    Aluminum may be pathogenic in the osteomalacia observed in some patients receiving hemodialysis. To study the early effects of Al on bone growth, bone formation, mineralization, and resorption were measured during short-term Al exposure in the tibial cortex of pair-fed control (C, n = 10), aluminum-treated (AL, n = 9), subtotally nephrectomized control (NX-C, n = 7), and subtotally nephrectomized aluminum-treated (NX-AL, n = 8) rats using double tetracycline labeling of bone. Animals received...

  17. Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

    OpenAIRE

    Jodi A. Carlson Scholz; Agnès Vignery; James Gilligan; Nozer Mehta; Xiaoqing Xu; Christopher Miller; Jesse Bible; Jiliang Li; Qing Zhang,

    2012-01-01

    Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH o...

  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. 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. PMID:24460696

  20. 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

  1. A novel mouse model for the study of the inhibitory effects of chronic ethanol exposure on direct bone formation

    Science.gov (United States)

    Excessive alcohol consumption has been reported to interfere with human bone homeostasis and repair in multiple ways. Previous studies have demonstrated that chronic ethanol exposure in the rat via an intragastric dietary delivery system inhibits direct bone formation during distraction osteogenesis...

  2. 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

  3. Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium

    Institute of Scientific and Technical Information of China (English)

    Audrey Rakian; Wu-Chen Yang; Jelica Gluhak-Heinrich; Yong Cui; Marie A Harris; Demitri Villarreal; Jerry Q Feng; Mary MacDougall; Stephen E Harris

    2013-01-01

    Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey’s fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp71 (Osterix1) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and a-SMA1 cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOSp7-Cre-EGFP. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOSp7-Cre-EGFP. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.

  4. Multiple myeloma presenting as plasmacytoma of the jaws showing prominent bone formation during chemotherapy.

    Science.gov (United States)

    An, S-Y; An, C-H; Choi, K-S; Heo, M-S

    2013-01-01

    A 65-year-old female visited our hospital complaining of a swelling on the left cheek area of 2 years' duration. A panoramic radiograph revealed an ill-defined osteolytic radiolucent bony lesion involving the left mandibular angle, ascending ramus, coronoid process and condylar process. Histological examination showed the mandibular lesion to be a plasmacytoma, and a systemic work-up was obtained to rule out multiple myeloma. Contrast-enhanced CT images showed a well-defined and slightly enhanced round mass on the left ramal area, accompanied by the destruction of the left ramus and posterior maxilla. An (18)F-fluorodeoxy-glucose positron emission tomography CT ((18)F-FDG PET/CT) scan revealed a hypermetabolic mass extending from the left mandible to the left maxillary sinus. The patient had M-protein in serum and urine, plasma cells up to 36.5% on bone marrow biopsy and anaemia as a clinical complication. The patient was diagnosed with multiple myeloma and received chemotherapy with thalidomide, cyclophosphamide and dexamethasone. A PET/CT scan taken 6 months later revealed that the hypermetabolic mass had disappeared and there was remarkable bone formation on the left mandible compared with a previous PET/CT scan. A panoramic radiograph taken 8 months later also demonstrated a prominent bone formation of the affected site. To the best of our knowledge, the current case is the first report of multiple myeloma presenting as plasmacytoma of the mandible with an FDG PET/CT scan. The lesion was solitary at diagnosis, and remarkable bone formation was newly observed on the radiographic examination during chemotherapy. PMID:23520399

  5. Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using {sup 18F} FDG PET/CT and {sup 99mT}c HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with of without soft tissue formation from HCC. of 4,151 patients with HCC, 263 patients had bone metastases. Eighty five patients with bone metastasis from HCC underwent contrast enhanced FDG PET/CT. Fifty four of the enrolled subjects had recent {sup 99mT}c HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow up studies. Forty seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft tissue formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher SUVmax (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non soft tissue formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion based analysis (98 vs. 53%, p=0.0015) and in patient based analysis (100 vs. 80%, p<0.001). Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast enhanced PET/CT will be useful in finding and delineating soft tissue forming bone metastasis from HCC.

  6. 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.......7 ± 1.9 and 2.4 ± 2.9 %, respectively, in SOC, with a greater (P < 0.05) change in SOC than in MS and C, whereas total body and total leg BMD did not change in any of the groups. CONCLUSION: In conclusion, 15 weeks of 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....

  7. Long-Term Symptoms Onset and Heterotopic Bone Formation around a Total Temporomandibular Joint Prosthesis: a Case Report

    OpenAIRE

    Luca Guarda-Nardini; Daniele Manfredini; Marco Olivo; Giuseppe Ferronato

    2014-01-01

    Background: The literature on total alloplastic temporomandibular joint (TMJ) reconstructions is encouraging, and studies on total alloplastic TMJ replacements outcomes showed acceptable improvements in terms of both pain levels and jaw function. Nevertheless, some adverse events, such as heterotopic bone formation around the implanted prosthesis, may occur. In consideration of that, the present manuscript describes a case of heterotopic bone formation around a total temporomandibular joint p...

  8. Long-Term Symptoms Onset and Heterotopic Bone Formation around a Total Temporomandibular Joint Prosthesis: a Case Report

    OpenAIRE

    Guarda-Nardini, Luca; Manfredini, Daniele; Olivo, Marco; Ferronato, Giuseppe

    2014-01-01

    ABSTRACT Background The literature on total alloplastic temporomandibular joint (TMJ) reconstructions is encouraging, and studies on total alloplastic TMJ replacements outcomes showed acceptable improvements in terms of both pain levels and jaw function. Nevertheless, some adverse events, such as heterotopic bone formation around the implanted prosthesis, may occur. In consideration of that, the present manuscript describes a case of heterotopic bone formation around a total temporomandibular...

  9. Structure and formation of the twisted plywood pattern of collagen fibrils in rat lamellar bone.

    Science.gov (United States)

    Yamamoto, Tsuneyuki; Hasegawa, Tomoka; Sasaki, Muneteru; Hongo, Hiromi; Tabata, Chihiro; Liu, Zhusheng; Li, Minqi; Amizuka, Norio

    2012-04-01

    This study was designed to elucidate details of the structure and formation process of the alternate lamellar pattern known to exist in lamellar bone. For this purpose, we examined basic internal lamellae in femurs of young rats by transmission and scanning electron microscopy, the latter employing two different macerations with NaOH at concentrations of 10 and 24%. Observations after the maceration with 10% NaOH showed that the regular and periodic rotation of collagen fibrils caused an alternation between two types of lamellae: one consisting of transversely and nearly transversely cut fibrils, and the other consisting of longitudinally and nearly longitudinally cut fibrils. This finding confirms the consistency of the twisted plywood model. The maceration method with 24% NaOH removed bone components other than cells, thus allowing for three-dimensional observations of osteoblast morphology. Osteoblasts extended finger-like processes paralleling the inner bone surface, and grouped in such a way that, within a group, the processes arranged in a similar direction. Transmission electron microscopy showed that newly deposited fibrils were arranged alongside these processes. For the formation of the alternating pattern, our findings suggest that: (1) osteoblasts control the collagen fibril arrangement through their finger-like process position; (2) osteoblasts behave similarly within a group; (3) osteoblasts move their processes synchronously and periodically to promote alternating different fibril orientation; and (4) this dynamic sequential deposition of fibrils results in the alternate lamellar (or twisted plywood) pattern. PMID:22362877

  10. Nanoscale control of silica particle formation via silk-silica fusion proteins for bone regeneration.

    Science.gov (United States)

    Mieszawska, Aneta J; Nadkarni, Lauren D; Perry, Carole C; Kaplan, David L

    2010-10-26

    The biomimetic design of silk/silica fusion proteins was carried out, combining the self assembling domains of spider dragline silk (Nephila clavipes) and silaffin derived R5 peptide of Cylindrotheca fusiformis that is responsible for silica mineralization. Genetic engineering was used to generate the protein-based biomaterials incorporating the physical properties of both components. With genetic control over the nanodomain sizes and chemistry, as well as modification of synthetic conditions for silica formation, controlled mineralized silk films with different silica morphologies and distributions were successfully generated; generating 3D porous networks, clustered silica nanoparticles (SNPs), or single SNPs. Silk serves as the organic scaffolding to control the material stability and multiprocessing makes silk/silica biomaterials suitable for different tissue regenerative applications. The influence of these new silk-silica composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on the silk/silica films. The presence of the silica in the silk films influenced osteogenic gene expression, with the upregulation of alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col 1) markers. Evidence for early bone formation as calcium deposits was observed on silk films with silica. These results indicate the potential utility of these new silk/silica systems towards bone regeneration. PMID:20976116

  11. Kartogenin induces cartilage-like tissue formation in tendon–bone junction

    Science.gov (United States)

    Zhang, Jianying; Wang, James H-C

    2014-01-01

    Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

  12. Kartogenin induces cartilage-like tissue formation in tendon-bone junction

    Institute of Scientific and Technical Information of China (English)

    Jianying Zhang; James H-C Wang

    2014-01-01

    Tendon-bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs.

  13. Kartogenin induces cartilage-like tissue formation in tendon-bone junction.

    Science.gov (United States)

    Zhang, Jianying; Wang, James H-C

    2014-01-01

    Tendon-bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

  14. 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.

  15. Development of a bone tissue-engineered construct to enhance new bone formation in revision total hip replacement

    OpenAIRE

    García Gareta, E.

    2012-01-01

    The main issue associated with revision total hip replacements (rTHRs) is how to generate new bone and restore bone stock for fixation of the revision stem. Bone tissue engineering (BTE) seeks the generation of constructs ex vivo in order to replace damaged or lost bone. The aim of this thesis was to develop a bone tissue-engineered construct with a calcium-phosphate (CaP) coated porous metal scaffold seeded throughout its structure with mesenchymal stem cells (MSCs) in order to enhance new b...

  16. EFFECTS OF XW630 ON BONE FORMATION IN OVARIECTOMIZED RATS AND IN HUMAN OSTEOBLAST-LIKE CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To study the effects of XW630 on bone formation in overiectomized(OVX) rats and in human osteoblast-like cell line TE85.Method. Bone histomorphometric analysis was performed with undecalcified bone sections and tetracycline intraperitoneally labeling.Results. Compared with that of OVX rats, the static data of trabecular bone volume(TBV)/ total tissue volume(TTV), TBV/sponge bone volume(SBV) and mean trabecular plate density (MTPD) were enhanced while mean trabecular plate spacing(MTPS) decreased after treated with XW630 for 13w. The dynamic data of single-labeled surface [Sfract(s)], double-labeled surface[Sfract(d)],Sfract(d+1/2s),trabecular osteoid surface(TOS), and bone formation rate in tissue level (Svf) were increased and osteoid maturation period (OMP) shortened in XW630 group. In osteoblast-like cells, both 3H-thymidine incorporation and cell count increased after treated with XW630 for 48. Treated with XW630 for 12~18h,inducible nitric oxide synthase(iNOS) activity and cGMP content increased in time-dependent manners.Conclusions. XW630 enhanced bone activation frequency and increased trabecular connectivity, stability, and strength. The cellular mechanism related to effects of XW630 on bone formation in ovariectomized rats.

  17. 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.

  18. Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties

    International Nuclear Information System (INIS)

    Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy

  19. 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

    2015-05-01

    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. PMID:25969194

  20. Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.

    Science.gov (United States)

    Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

    2012-06-01

    Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss. PMID:22436700

  1. Osteoblast-Specific γ-Glutamyl Carboxylase-Deficient Mice Display Enhanced Bone Formation With Aberrant Mineralization.

    Science.gov (United States)

    Azuma, Kotaro; Shiba, Sachiko; Hasegawa, Tomoka; Ikeda, Kazuhiro; Urano, Tomohiko; Horie-Inoue, Kuniko; Ouchi, Yasuyoshi; Amizuka, Norio; Inoue, Satoshi

    2015-07-01

    Vitamin K is a fat-soluble vitamin that is necessary for blood coagulation. In addition, it has bone-protective effects. Vitamin K functions as a cofactor of γ-glutamyl carboxylase (GGCX), which activates its substrates by carboxylation. These substrates are found throughout the body and examples include hepatic blood coagulation factors. Furthermore, vitamin K functions as a ligand of the nuclear receptor known as steroid and xenobiotic receptor (SXR) and its murine ortholog, pregnane X receptor (PXR). We have previously reported on the bone-protective role of SXR/PXR signaling by demonstrating that systemic Pxr-knockout mice displayed osteopenia. Because systemic Ggcx-knockout mice die shortly after birth from severe hemorrhage, the GGCX-mediated effect of vitamin K on bone metabolism has been difficult to evaluate. In this work, we utilized Ggcx-floxed mice to generate osteoblast-specific GGCX-deficient (Ggcx(Δobl/Δobl)) mice by crossing them with Col1-Cre mice. The bone mineral density (BMD) of Ggcx(Δobl/Δobl) mice was significantly higher than that of control Col1-Cre (Ggcx(+/+)) mice. Histomorphometrical analysis of trabecular bones in the proximal tibia showed increased osteoid volume and a higher rate of bone formation in Ggcx(Δobl/Δobl) mice. Histomorphometrical analysis of cortical bones revealed a thicker cortical width and a higher rate of bone formation in Ggcx(Δobl/Δobl) mice. Electron microscopic examination revealed disassembly of mineralized nodules and aberrant calcification of collagen fibers in Ggcx(Δobl/Δobl) mice. The mechanical properties of bones from Ggcx(Δobl/Δobl) mice tended to be stronger than those from control Ggcx(+/+) mice. These results suggest that GGCX in osteoblasts functions to prevent abnormal mineralization in bone formation, although this function may not be a prerequisite for the bone-protective effect of vitamin K. PMID:25600070

  2. Free Radicals Formation of Irradiated Lyophilized Can-Cellous Human and Bovine Bone

    International Nuclear Information System (INIS)

    Radiation sterilization of lyophilized human and bovine bone as allograft and xenograft have been produced and used in orthopaedic practice in Indonesia routinely. It is well known from radio biologic studies that one of the most pronounce effects of ionizing radiation on biologic species produced the free radicals that influence the physico-chemical as well as the mechanical properties of irradiated bone. The aim of our study is to investigate the free radicals formation of irradiated lyophilized cancellous triple A bone (Autolyzed Antigen-Extracted Allograft) produced by Batan Research Tissue Bank in Jakarta. The cancellous triple A were prepared according to AATB (American Association of Tissue Bank) method. Gamma Irradiations was done at doses of 10, 20 and 30 kGy with a dose rate of 7,5 kGy/h at room temperature (30oC± 2oC). Measurements of free radicals was done at 24oC ±1oC within 30 minutes after irradiational and measurement were continued up to 9 months of storage using a JES-REIX ESR Spectrophotometer (JEOL) with Mn exp. ++ standard. Parameters measured, were the effects of mechanical grinding, water immersion and irradiation dose on free radicals formation in the bone. Results show that the signal area of ESR spectra from irradiated bovine bone of 30 kGy was higher than those of human bone I.e. 1,4 x 10 exp. 7 dan 6,4 x 10 exp. 6 Au (arbitrary unit)/g samples respectively. The signal of ESR spectra increased linearly with increasing dose in the range of 10-30 kGy and it will reduce about 30% caused by water immersion. The ESR signal reduced sharply after 2 days and gradually decreased up to 14 days and then became constant up to 9 months of storage at room temperature. A certain method of crushing can produce free radicals. Key Words: free radical, irradiation, allograft, xenograft, mechanical-grinding

  3. The effects of 3D bioactive glass scaffolds and BMP-2 on bone formation in rat femoral critical size defects and adjacent bones

    International Nuclear Information System (INIS)

    Reconstruction of critical size defects in the load-bearing area has long been a challenge in orthopaedics. In the past, we have demonstrated the feasibility of using a biodegradable load-sharing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. For this reason, 13-93 bioactive glass scaffolds with local BMP-2 delivery were investigated in this study for inducing segmental defect repairs in a load-bearing region. Furthermore, a recent review on BMP-2 revealed greater risks in radiculitis, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. We also evaluated the potential side effects of locally delivered BMP-2 on the structures of adjacent bones. Therefore, cylindrical 13-93 glass scaffolds were fabricated by indirect selective laser sintering with side holes on the cylinder filled with dicalcium phosphate dehydrate as a BMP-2 carrier. The scaffolds were implanted into critical size defects created in rat femurs with and without 10 μg of BMP-2. The x-ray and micro-CT results showed that a bridging callus was found as soon as three weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. Degradation of the scaffolds was noted in both groups. Stiffness, peak load and energy to break of the BMP group were all higher than the control group. There was no statistical difference in bone mineral density, bone area and bone mineral content in the tibiae and contralateral femurs of the control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects. (paper)

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

    International Nuclear Information System (INIS)

    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)

  5. Human Osteoblast Differentiation and Bone Formation: Growth Factors, Hormones and Regulatory Networks

    OpenAIRE

    Eijken, Marco

    2007-01-01

    textabstractOsteoporosis is the most common bone disease and is characterized by low bone mass, micro architectural deterioration and decreased bone quality resulting in increased risk of fractures. Osteoblasts, the bone forming cells, play a crucial role in the regulation of bone mass and bone quality. Osteoblasts are of mesenchymal origin and undergo a complex differentiation process regulated by many endocrine and autocrine factors. In order to develop novel bone anabolic drugs, more knowl...

  6. 18F]fluoride PET indicates reduced bone formation in severe glucocorticoid-induced osteoporosis

    International Nuclear Information System (INIS)

    A 61-year-old female patient presenting with mixed connective tissue disease (Sharp syndrome), underwent a long-term high dose glucocordicoid treatment because of multiple organ manifestations. Under steroid therapy she developed severe osteoporosis resulting in multiple fractures. A dynamic [18F]fluoride PET study in this patient revealed reduced fluoride influx in non-fractured vertebrae. This finding corresponds to pathogenetic concepts which propose an inhibition of bone formation as major cause of glucocorticoid-induced osteoporosis. In the light of the presented case it seems to be promising to evaluate the diagnostic benefit of [18F]fluoride PET in osteoporosis. (orig.)

  7. X-ray studies on the change in bone formation in fractures following laser treatment

    International Nuclear Information System (INIS)

    An important problem, associated with the X-ray studies of the changes in bone formation in fractures following laser treatment, is dicussed. Results are reported on laser therapy of 30 patients with fractures of the radius in loco typico and compared with a control group of 30 patients, who were treated with ordinary (laboratory) lamp with a side light beam. It was found that laser biostimulation activated callus development in fractures and speeded their complete consolidation. In laser-treated patients osteoporosis occured more seldom and had predominantly limited and patchy appearance, while Sudek's osteoporosis was seen mainly in the control group

  8. Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

    Directory of Open Access Journals (Sweden)

    Jodi A. Carlson Scholz

    2012-12-01

    Full Text Available Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH. Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.

  9. Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.

    Directory of Open Access Journals (Sweden)

    Marta Kisiel

    Full Text Available Bone morphogenetic protein-2 (BMP-2 is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs dermatan sulfate (DS or heparin (HP, prior to loading it into a hyaluronic acid (HA hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG.

  10. 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.

  11. A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation

    DEFF Research Database (Denmark)

    Thudium, Christian S; Moscatelli, Ilana; Flores, Carmen; Thomsen, Jesper Skovhus; Brüel, Annemarie; Gudmann, Natasja Stæhr; Hauge, Ellen Margrethe; Karsdal, Morten A; Richter, Johan; Henriksen, Kim

    2014-01-01

    formation rate (54 %) in trabecular bone, while RANK KO recipients showed only minor trends compared to control recipients. We here show that maintaining non-resorbing osteoclasts, as opposed to reducing the osteoclasts, leads to increased bone formation, bone volume, and ultimately higher bone strength in......Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating......-poor adult osteopetrosis model. We used fetal liver HSCs from (1) oc/oc mice, (2) RANK KO mice, and (3) compared these to wt control cells. TRAP5b activity, a marker of osteoclast number and size, was increased in the oc/oc recipients, while a significant reduction was seen in the RANK KO recipients. In...

  12. The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

    Science.gov (United States)

    Halloran, B. P.; Bikle, D. D.; Wronski, T. J.; GLOBUS. R.; Levens, M. J.; Morey-Holton, E.

    1983-01-01

    Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus (P sub i), 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D (24,25(OH)2D and 1,25-dihydroxyvitamin D (1,25(OH)2D. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P 0.01), a 32% decrease in bone surface lined with osteoblasts (P .05), no change in bone surface lined with osteoclasts and a decrease in circulating (1,25(OH)2D. No significant changes in the serum concentrations of P sub i, 25-OH-D or 24,25(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control and serum Ca and 1,25(OH)2D returned to control values. Maintenance of a constant serum 1,25(OH)2D concentration by chronic infusion of 1,25(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation which in turn produces a transitory hypercalcemia.

  13. Influence of B-lymphocytes from various organs on hemopoietic colony formation in the spleen by bone marrow cells

    International Nuclear Information System (INIS)

    The influence of B-lymphocytes from various sources on splenic colony formation was studied in the syngeneic system. Splenic, but not bone marrow and lymph node B-cells inhibited colony formation by combination of Sc-1- and Sc-1+ cells. All effects of Ig+ cells were abolished by treatment of cells with rabbit anti-MBLA serum. Thus, B-cells of various origin can either enhance or inhibit colony formation. The enhancing of inhibitory effect after B (MBLA+)-cells elimination from suspension of bone marrow and lymph node (but not spleen) Ig+-cells resulted from the activity of B-contrasuppressors

  14. Ectopic bone formation using an injectable biphasic calcium phosphate/Si-HPMC hydrogel composite loaded with undifferentiated bone marrow stromal cells.

    Science.gov (United States)

    Trojani, Christophe; Boukhechba, Florian; Scimeca, Jean-Claude; Vandenbos, Fanny; Michiels, Jean-François; Daculsi, Guy; Boileau, Pascal; Weiss, Pierre; Carle, Georges F; Rochet, Nathalie

    2006-06-01

    We have used a new synthetic injectable composite constituted of hydroxyapatite/tricalcium phosphate (HA/TCP) particles in suspension in a self-hardening Si-hydroxypropylmethylcellulose (HPMC) hydrogel. The aim of this study was to evaluate in vivo the biocompatibility and the new bone formation efficacy of this scaffold loaded with undifferentiated bone marrow stromal cells (BMSCs). This biomaterial was mixed extemporaneously with BMSCs prepared from C57BL/6 mice, injected in subcutaneous and intramuscular sites and retrieved 4 and 8 weeks after implantation. Dissection of the implants revealed a hard consistency and the absence of a fibrous capsule reflecting a good integration into the host tissues. Histological analysis showed mineralized woven bone in the granule inter-space with numerous active osteoclasts attached to the particles as assessed by the presence of multinucleated cells positively stained for TRAP activity and for the a3 subunit of the V-ATPase. Small vessels were homogenously distributed in the whole implants. Similar results were obtained in SC and IM sites and no bone formation was observed in the control groups when cell-free and particle-free transplants were injected. These results indicate that this injectable biphasic calcium phosphate-hydrogel composite mixed with undifferentiated BMSCs is a new promising osteoinductive bone substitute. It also provides with an original in vivo model of osteoclast differentiation and function. PMID:16510180

  15. cAMP/PKA signaling inhibits osteogenic differentiation and bone formation in rodent models.

    Science.gov (United States)

    Siddappa, Ramakrishnaiah; Mulder, Winfried; Steeghs, Ilse; van de Klundert, Christine; Fernandes, Hugo; Liu, Jun; Arends, Roel; van Blitterswijk, Clemens; de Boer, Jan

    2009-08-01

    We previously demonstrated that cAMP-mediated protein kinase A (PKA) activation induces in vitro osteogenesis and in vivo bone formation by human mesenchymal stem cells (hMSCs). To analyze the species-specific response of this phenomenon and to translate our findings into a clinical trial, suitable animal models and cell lines are desirable. In this report, we assessed whether PKA plays a similar proosteogenic role played by two commonly used PKA activators-N6,2'-O-dibutyryl-cAMP (db-cAMP) and 8-bromo cAMP (8b-cAMP)-in a number of model systems. To this end, we treated MC3T3-E1 cells, mouse calvarial osteoblasts, mouse MSCs, and rat MSCs with cAMP. We demonstrate that cAMP inhibits osteogenesis in rodent cell types, evidenced by inhibition of osteogenic markers such as alkaline phosphatase (ALP), osteocalcin (BGLAP), and collagen type 1 (COL1A1). In support of this, ex vivo-cultured mouse calvaria exposed to db-cAMP showed a reduction in bone volume. Interestingly, cAMP even stimulated adipogenic differentiation in rat MSCs. Taken together, our data demonstrate that cAMP inhibits osteogenesis in vitro and bone formation ex vivo in rodent models in contrast to our earlier findings in hMSCs. The species discrepancy in response to various osteogenic signals is a critical need to be tested in clinically relevant models to translate the fundamental findings in lower species level to clinical applications. PMID:19231969

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Exploring pre-service science teachers' pedagogical capacity for formative assessment through analyses of student answers

    Science.gov (United States)

    Aydeniz, Mehmet; Dogan, Alev

    2016-05-01

    Background: There has been an increasing emphasis on empowering pre-service and in-service science teachers to attend student reasoning and use formative assessments to guide student learning in recent years. Purpose: The purpose of this study was to explore pre-service science teachers' pedagogical capacity for formative assessment. Sample: This study took place in Turkey. The participants include 53 pre-service science teachers in their final year of schooling. All but two of the participants are female. Design and methods: We used a mixed-methods methodology in pursing this inquiry. Participants analyzed 28 responses to seven two-tiered questions given by four students of different ability levels. We explored their ability to identify the strengths and weaknesses in students' answers. We paid particular attention to the things that the pre-service science teachers noticed in students' explanations, the types of inferences they made about students' conceptual understanding, and the affordances of pedagogical decisions they made. Results: The results show that the majority of participants made an evaluative judgment (i.e. the answer is correct or incorrect) in their analyses of students' answers. Similarly, the majority of the participants recognized the type of mistake that the students made. However, they failed to successfully elaborate on fallacies, limitations, or strengths in student reasoning. We also asked the participants to make pedagogical decisions related to what needs to be done next in order to help the students to achieve academic objectives. Results show that 8% of the recommended instructional strategies were of no affordance, 64% of low-affordance, and 28% were of high affordance in terms of helping students achieve the academic objectives. Conclusion: If our goal is to improve pre-service science teachers' noticing skills, and the affordance of feedback that they provide, engaging them in activities that asks them to attend to students' ideas

  18. Very-long-chain fatty acids restrict regeneration capacity by confining pericycle competence for callus formation in Arabidopsis.

    Science.gov (United States)

    Shang, Baoshuan; Xu, Chongyi; Zhang, Xixi; Cao, Huifen; Xin, Wei; Hu, Yuxin

    2016-05-01

    The already differentiated organs in plants have a remarkable capacity to regenerate new individuals under culture conditions. Plant in vitro regeneration practically starts with the induction of a pluripotent cell mass, the callus, from detached organs on auxin-rich callus-inducing medium (CIM), which is generally required for subsequent regeneration of new bodies. Recent studies show that CIM-induced callus formation occurs from the pericycle or pericycle-like cells through a root developmental pathway, whereas the signals involved in governing callus-forming capacity of pericycle cells remain unknown. Here we report that very-long-chain fatty acids (VLCFAs) play a critical role in confining the pericycle competence for callus formation and thus the regeneration capacity of Arabidopsis By genetic screening, we identified the callus formation-related 1 (cfr1) mutant, which bypasses the inhibition of callus-forming capacity in roots by solitary-root (slr/iaa14). We show that CFR1 encodes 3-ketoacyl-CoA synthase 1 (KCS1), which catalyzes a rate-limiting step of VLCFA biosynthesis. Our biochemical and genetic analyses demonstrate that VLCFAs restrict the pericycle competence for callus formation, at least in part, by regulating the transcription of Aberrant Lateral Root Formation 4 (ALF4). Moreover, we provide evidence that VLCFAs act as cell layer signals to mediate the pericycle competence for callus formation. Taken together, our results identify VLCFAs or their derivatives as the confining signals for mediating the pericycle competence for callus formation and thus the regeneration capacity of plant organs. PMID:27092001

  19. The remodeling pattern of human mandibular alveolar bone during prenatal formation from 19 to 270mm CRL.

    Science.gov (United States)

    Radlanski, Ralf J; Renz, Herbert; Tsengelsaikhan, Nyamdorj; Schuster, Felix; Zimmermann, Camilla A

    2016-05-01

    The underlying mechanisms of human bone morphogenesis leading to a topologically specific shape remain unknown, despite increasing knowledge of the basic molecular aspects of bone formation and its regulation. The formation of the alveolar bone, which houses the dental primordia, and later the dental roots, may serve as a model to approach general questions of bone formation. Twenty-five heads of human embryos and fetuses (Radlanski-Collection, Berlin) ranging from 19mm to 270mm (crown-rump-length) CRL were prepared as histological serial sections. For each stage, virtual 3D-reconstructions were made in order to study the morphogenesis of the mandibular molar primordia with their surrounding bone. Special focus was given to recording the bone-remodeling pattern, as diagnosed from the histological sections. In early stages (19-31mm CRL) developing bone was characterized by appositional only. At 41, in the canine region, mm CRL bony extensions were found forming on the bottom of the trough. Besides general apposition, regions with resting surfaces were also found. At a fetal size of 53mm CRL, septa have developed and led to a compartment for canine development. Furthermore, one shared compartment for the incisor primordia and another shared compartment for the molars also developed. Moreover, the inner surfaces of the dental crypts showed resorption of bone. From this stage on, a general pattern became established such that the compartmentalizing ridges and septa between all of the dental primordia and the brims of the crypts were noted, and were due to appositional growth of bone, while the crypts enlarged on their inner surfaces by resorption. By 160mm CRL, the dental primordia were larger, and all of the bony septa had become reduced in size. The primordia for the permanent teeth became visible at 225mm CRL and shared the crypts of their corresponding deciduous primordia. PMID:26921449

  20. Culture medium of bone marrow-derived human mesenchymal stem cells effects lymphatic endothelial cells and tumor lymph vessel formation

    OpenAIRE

    ZHAN, JIE; Li, Yahong; Yu, Jing; ZHAO, YUANYAUN; CAO, WENMING; Ma, Jie; Sun, Xiaoxian; Sun, Li; QIAN, HUI; Zhu, Wei; Xu, Wenrong

    2015-01-01

    Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet...

  1. 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. PMID:26707938

  2. The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice.

    Directory of Open Access Journals (Sweden)

    Edgardo Rodríguez-Carballo

    Full Text Available p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified.We evaluated osteoblast-specific deletion of p38α to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38α deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38α did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38α disruption after birth by removal of doxycycline. Deletion of p38α at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months.Our data demonstrates that, in addition to early skeletogenesis, p38α is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects.

  3. 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...... implant were not significantly different among the four groups. The ABM/P-15 group had similar shear mechanical properties on implant fixation as the allograft group. Adding HA/βTCP-PDLLA to ABM/P-15 did not significantly change these parameters. This study revealed that ABM/P-15 had significantly bone...

  4. Conditional Deletion of BMP7 from the Limb Skeleton Does Not Affect Bone Formation or Fracture Repair

    OpenAIRE

    Tsuji, Kunikazu; Cox, Karen; Gamer, Laura; Graf, Daniel; Economides, Aris; Rosen, Vicki

    2010-01-01

    While the osteoinductive activity of recombinant bone morphogenetic protein 7 (BMP7) is well established, evaluation of the role of endogenous BMP7 in bone formation and fracture healing has been hampered by perinatal lethality in BMP7 knockout mice. Here we employ conditional deletion of BMP7 from the embryonic limb prior to the onset of skeletogenesis to create limb bones lacking BMP7. We find that the absence of locally produced BMP7 has no effect on postnatal limb growth, articular cartil...

  5. Evaluation of complex formation ability of dissolved organic matter with radionuclide in ground water based on loading capacity (LC) method

    International Nuclear Information System (INIS)

    It is important to evaluate complex formation ability of dissolved organic matter (DOM) with radionuclide, in terms of long-term safety assessment of nuclear waste. In this review, the dependence of the complex stability on environmental factors such as pH, ionic strength, and characteristics of humic substances was described based on Loading Capacity (LC) method. The effects of humic concentration on actinide speciation and its solubility in a groundwater were evaluated with consideration of mixed complex formation. (author)

  6. Effect of xenograft (ABBM) particle size on vital bone formation following maxillary sinus augmentation: a multicenter, randomized, controlled, clinical histomorphometric trial.

    Science.gov (United States)

    Testori, Tiziano; Wallace, Stephen S; Trisi, Paolo; Capelli, Matteo; Zuffetti, Francesco; Del Fabbro, Massimo

    2013-01-01

    The purpose of this study was a histomorphometric comparison of vital bone formation following maxillary sinus augmentation with two different particle sizes of anorganic bovine bone matrix (ABBM). Bilateral sinus floor augmentations were performed in 13 patients. Trephine bone cores were taken from the lateral window areas of 11 patients 6 to 8 months after augmentation for histologic and histomorphometric analysis. Bone samples from both the large and small particle size groups showed evidence of vital bone formation similar to that seen in previous studies, confirming the osteoconductivity of ABBM. Significant bone bridging was seen creating new trabeculae composed of the newly formed bone and residual ABBM particles. Histologic evaluation revealed the newly formed bone to be mostly woven bone with some remodeling to lamellar bone. Osteocytes were seen within the newly formed bone as well as osteoblast seams with recently formed osteoid. Isolated osteoclasts were observed on the ABBM surfaces. Vital bone formation (primary outcome measure) was more extensive in the large particle grafts compared with the small particle grafts (26.77% ± 9.63% vs 18.77% ± 4.74%, respectively). The histologic results reaffirm the osteoconductive ability of ABBM when used as the sole grafting material in maxillary sinus augmentation. The histomorphometric results at 6 to 8 months revealed a statistically significant increase (P = .02) in vital bone formation when the larger particle size was used. Additional studies should be performed to confirm these results. PMID:23820706

  7. Class I PI-3-Kinase Signaling Is Critical for Bone Formation Through Regulation of SMAD1 Activity in Osteoblasts.

    Science.gov (United States)

    Gámez, Beatriz; Rodríguez-Carballo, Edgardo; Graupera, Mariona; Rosa, José Luis; Ventura, Francesc

    2016-08-01

    Bone formation and homeostasis is carried out by osteoblasts, whose differentiation and activity are regulated by osteogenic signaling networks. A central mediator of these inputs is the lipid kinase phosphatidylinositol 3-kinase (PI3K). However, at present, there are no data on the specific role of distinct class IA PI3K isoforms in bone biology. Here, we performed osteoblast-specific deletion in mice to show that both p110α and p110β isoforms are required for survival and differentiation and function of osteoblasts and thereby control bone formation and postnatal homeostasis. Impaired osteogenesis arises from increased GSK3 activity and a depletion of SMAD1 protein levels in PI3K-deficient osteoblasts. Accordingly, pharmacological inhibition of GSK3 activity or ectopic expression of SMAD1 or SMAD5 normalizes bone morphogenetic protein (BMP) transduction and osteoblast differentiation. Together, these results identify the PI3K-GSK3-SMAD1 axis as a central node integrating multiple signaling networks that govern bone formation and homeostasis. © 2016 American Society for Bone and Mineral Research. PMID:26896753

  8. TEI-3313, a novel prostaglandin A1 derivative, prevents bone loss and enhances bone formation in immobilized male rats.

    Science.gov (United States)

    Ohta, T; Azuma, Y; Kanatani, H; Kiyoki, M; Koshihara, Y

    1995-10-01

    The effect of a novel prostaglandin A1 derivative, TEI-3313, with the chemical structure 5-[(Z,2E)-4,7-dihydroxy-2-heptenyridene]-4-hydroxy- 2-methylthio-4-(4-phenoxybutyl)-2-cyclopentenone, on bone mineral content was investigated. Seven-week-old Sprague-Dawley rats in which the right hindlimbs were immobilized by sciatic nerve dissection received 1, 10, 100 or 500 micrograms of TEI-3313/kg/day, i.p., for 6 weeks. Control animals were operated on but received vehicle only. Bone mineral content of the femur was measured by single-photon absorptiometry, and biochemical parameters were analyzed. Histomorphometric observations were performed on the proximal metaphysial sections of the tibiae. The administration of up to 500 micrograms/kg of TEI-3313 to rats had no effect on body weight or on serum calcium, inorganic phosphorus and 1 alpha,25 dihydroxy vitamin D3 levels. Immobilization decreased the ash content, calcium content and total bone mineral content of the femur compared with nonimmobilization (unoperated femur). With TEI-3313 administration, changes in these parameters in the immobilized femur were prevented almost to the levels of the nonimmobilized femur, in a dose-dependent manner. The enhancement of bone mineral content was remarkable in the midshaft of the femur. TEI-3313 enhanced ash and calcium content and total bone mineral content in nonimmobilized femurs. Microradiograms showed that TEI-3313, unlike pamidronate and 17 beta-estradiol, had little inhibitory effect on trabecular bone resorption in the proximal portion of the tibia. TEI-3313 not only prevented the bone loss induced by immobilization but also increased bone mass in the nonimmobilized femurs without affecting the levels of 1 alpha,25 dihydroxy vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7562584

  9. A Longitudinal Study of the Effect of Genistein on Bone in Two Different Murine Models of Diminished Estrogen-Producing Capacity

    OpenAIRE

    Stephen Barnes; Turner, Charles H.; Hoyer, Patricia B.; Mayer, Loretta P.; Susan Reinwald; Weaver, Connie M.

    2010-01-01

    This experiment was designed to assess the capacity of dietary genistein (GEN), to attenuate bone loss in ovariectomized (OVX) and ovary-intact VCD-treated mice. Pretreatment of mice with 4-vinylcyclohexene diepoxide (VCD) gradually and selectively destroys ovarian follicles whilst leaving ovarian androgen-producing cells largely intact. VCD induces a perimenopause-like condition prior to the onset of reproductive acyclicity. Sixteen-week-old C57BL/6J mice were randomized to five treatment gr...

  10. The combined mechanism of bone morphogenetic protein- and calcium phosphate-induced skeletal tissue formation by human periosteum derived cells.

    Science.gov (United States)

    Bolander, J; Ji, W; Geris, L; Bloemen, V; Chai, Y C; Schrooten, J; Luyten, F P

    2016-01-01

    When combining osteogenic progenitor cells such as human periosteum derived cells (hPDCs) with osteoconductive biomaterials like calcium phosphate (CaP)-scaffolds, in vivo bone formation can be achieved. This process is dependent on the early activation of Bone morphogenetic protein (BMP)-signalling. However, the bone forming process is slow and routinely only a limited amount of bone and bone marrow is formed. Therefore, we hypothesised that a robust clinically relevant outcome could be achieved by adding more physiological levels of potent BMP-ligands to these cell- and CaP-based constructs. For this, hPDCs were characterised for their responsiveness to BMP-ligands upon in vitro 2D stimulation. BMP-2, -4, -6 and -9 robustly induced osteochondrogenic differentiation. Subsequently, these ligands were coated onto clinically approved CaP-scaffolds, BioOss® and CopiOs®, followed by hPDC-seeding. Protein lysates and conditioned media were investigated for activation of BMP signalling pathways. Upon in vivo implantation, the most abundant bone formation was found in BMP-2 and BMP-6-coated scaffolds. Implanted cells actively contributed to the newly formed bone. Remnants of cartilage could be observed in BMP-coated CopiOs®-constructs. Computational analysis displayed that the type of BMP-ligand as well as the CaP-scaffold affects skeletal tissue formation, observed in a qualitative as well as quantitative manner. Furthermore, the in vitro mechanism appears to predict the in vivo outcome. This study presents further evidence for the potential of BMP-technology in the development of clinically relevant cell-based constructs for bone regenerative strategies. PMID:26728496

  11. Short-term intermittent PTH 1-34 administration enhances bone formation in SCID/Beige mice

    International Nuclear Information System (INIS)

    The anabolic effect of intermittent parathyroid hormone (PTH) on bone is variable depending on the species studied, duration/mode of administration, and location of skeletal response investigated. We tested the hypothesis that low dose, short term, intermittent PTH 1-34 administration is sufficient to enhance bone formation without altering bone resorption. To test our hypothesis, mice were treated intermittently with one of three concentrations of PTH 1-34 (1 μg/kg, low; 10μg/kg or 20 μg/kg, high) for three weeks. The skeletal response was identified by quantifying: serum markers of bone turnover, cancellous bone parameters in distal femur, proximal tibia, and lumbar vertebrae by μCT, and number of osteoblasts and osteoclasts in distal femur. Mice receiving 20 μg/kg of PTH 1-34 demonstrated a 30% increase in serum osteocalcin, but no differences in serum calcium, type I collagen teleopeptides, or tartrate resistant acid phosphatase (TRACP) 5b. For all bones, μCT analysis suggested mice receiving 20 μg/kg of PTH 1-34 had increased cancellous bone mineral density, trabecular thickness and spacing, but decreased trabecular number. A 60% increase in the number of alkaline phosphatase positive osteoblasts in the distal femur was also observed in tissue sections; however, the number of TRAP positive osteoclasts was not different between test and control groups. While animals administered 10 μg/kg demonstrated similar trends for all bone turnover indices, such alterations were not observed in animals administered PTH 1-34 at 1 μg/kg per day. Thus, PTH 1-34, administered intermittently for three weeks at 20 μg/kg is sufficient to enhance bone formation without enhancing resorption. (author)

  12. Charge-transfer complex formation in gelation: the role of solvent molecules with different electron-donating capacities.

    Science.gov (United States)

    Basak, Shibaji; Bhattacharya, Sumantra; Datta, Ayan; Banerjee, Arindam

    2014-05-01

    A naphthalenediimide (NDI)-based synthetic peptide molecule forms gels in a particular solvent mixture (chloroform/aromatic hydrocarbon, 4:1) through charge-transfer (CT) complex formation; this is evident from the corresponding absorbance and fluorescence spectra at room temperature. Various aromatic hydrocarbon based solvents, including benzene, toluene, xylene (ortho, meta and para) and mesitylene, have been used for the formation of the CT complex. The role of different solvent molecules with varying electron-donation capacities in the formation of CT complexes has been established through spectroscopic and computational studies. PMID:24677404

  13. The Impact of Immune System in Regulating Bone Metastasis Formation by Osteotropic Tumors

    Directory of Open Access Journals (Sweden)

    Lucia D’Amico

    2015-01-01

    Full Text Available Bone metastases are frequent and debilitating consequence for many tumors, such as breast, lung, prostate, and kidney cancer. Many studies report the importance of the immune system in the pathogenesis of bone metastasis. Indeed, bone and immune system are strictly linked to each other because bone regulates the hematopoietic stem cells from which all cells of the immune system derive, and many immunoregulatory cytokines influence the fate of bone cells. Furthermore, both cytokines and factors produced by immune and bone cells promote the growth of tumor cells in bone, contributing to supporting the vicious cycle of bone metastasis. This review summarizes the current knowledge on the interactions among bone, immune, and tumor cells aiming to provide an overview of the osteoimmunology field in bone metastasis from solid tumors.

  14. 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)

    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)

  15. Calcium Plasma Implanted Titanium Surface with Hierarchical Microstructure for Improving the Bone Formation.

    Science.gov (United States)

    Cheng, Mengqi; Qiao, Yuqin; Wang, Qi; Jin, Guodong; Qin, Hui; Zhao, Yaochao; Peng, Xiaochun; Zhang, Xianlong; Liu, Xuanyong

    2015-06-17

    Introducing hierarchical microstructure and bioactive trace elements simultaneously onto the surface of titanium implant is a very effective way to improve the osseointegration between bone and implant. In this work, hierarchical topography was prepared on Ti surface via acid etching and sandblasting (SLA) to form micropits and microcavities then underwent Ca plasma immersion ion implantation (Ca-PIII) process. The surface wettability and roughness did not change obviously before and after Ca-PIII process. The in vitro evaluations including cell adhesion, activity, alkaline phosphatase (ALP), osteogenic genes (Runx2, OSX, ALP, BSP, Col1a1, OPN, and OC), and protein (BSP, Col1a1, OPN, and OC) expressions revealed that the introduction of Ca ions onto the surface of SLA-treated Ti can promote greater osteoblasts adhesion, spread and proliferation, which in return further accelerated the maturation and mineralization of osteoblasts. More importantly, in vivo evaluations including Micro-CT evaluation, histological observations, push-out test, sequential fluorescent labeling and histological observations verified that Ca-SLA-treated Ti implants could efficiently promote new bone formation in early times. These promising results suggest that Ca-SLA-treated Ti has the potential for future application in orthopedic field. PMID:26020570

  16. The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family.

    Science.gov (United States)

    Ripamonti, Ugo; Parak, Ruqayya; Klar, Roland M; Dickens, Caroline; Dix-Peek, Thérèse; Duarte, Raquel

    2016-10-01

    The momentum to compose this Leading Opinion on the synergistic induction of bone formation suddenly arose when a simple question was formulated during a discussion session on how to boost the often limited induction of bone formation seen in clinical contexts. Re-examination of morphological and molecular data available on the rapid induction of bone formation by the recombinant human transforming growth factor-β3 (hTGF-β3) shows that hTGF-β3 replicates the synergistic induction of bone formation as invocated by binary applications of hOP-1:hTGF-β1 at 20:1 by weight when implanted in heterotopic sites of the rectus abdominis muscle of the Chacma baboon, Papio ursinus. The rapid induction of bone formation in primates by hTGF-β3 may stem from bursts of cladistic evolution, now redundant in lower animal species but still activated in primates by relatively high doses of hTGF-β3. Contrary to rodents, lagomorphs and canines, the three mammalian TGF-β isoforms induce rapid and substantial bone formation when implanted in heterotopic rectus abdominis muscle sites of P. ursinus, with unprecedented regeneration of full thickness mandibular defects with rapid mineralization and corticalization. Provocatively, thus providing potential molecular and biological rationales for the apparent redundancy of osteogenic molecular signals in primates, binary applications of recombinant human osteogenic protein-1 (hOP-1) with low doses of hTGF-β1 and -β3, synergize to induce massive ossicles in heterotopic rectus abdominis, orthotopic calvarial and mandibular sites of P. ursinus. The synergistic binary application of homologous but molecularly different soluble molecular signals has indicated that per force several secreted molecular signals are required singly, synchronously and synergistically to induce optimal osteogenesis. The morphological hallmark of the synergistic induction of bone formation is the rapid differentiation of large osteoid seams enveloping

  17. 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.

  18. Unusual presentation of glomus tympanicum tumour: New bone formation in the middle ear.

    Science.gov (United States)

    Kumar, Gaurav; Andreou, Zenon; Virk, Jagdeep Singh; Owa, Anthony

    2014-09-16

    The objective of this study is to increase awareness of the rare presentation, diagnostic difficulties and management of glomus tympanicum of the middle ear. A 49 years old male, with a background of hypertension and epilepsy, presented with a two month history of left sided conductive hearing loss, pulsatile tinnitus and headache. Clinically and radiologically a diagnosis of glomus tympanicum was made. Intraoperatively, extensive osteogenesis of the middle ear resulting in ossicular fixation and erosion was found. This patient required a two stage operation for full clearance of disease. A stapedectomy drill was used to drill off the bony overgrowth surrounding the ossicles resulting in improved hearing thresholds and full clearance of the disease at two year follow up. Glomus tympanicum can result in new bone formation in the middle ear with resultant ossicular fixation and conductive hearing loss. This can be effectively treated surgically with restoration of hearing. PMID:25232551

  19. Radiotherapy of heterotopic bone formation in patients with paraplegia. Preliminary results

    International Nuclear Information System (INIS)

    In 20 patients with paralysis, 25 regions were irradiated with (mostly) 10 Gy in single fractions of 2 to 2.5 Gy using 8 MW photons. In 15 patients radiotherapy was performed as a primary treatment in the status of myositis; 7 patients were treated after (subtotal) resection of already manifest ossifications (2 patients were treated twice, primarily and postoperatively). In a minimum follow-up 12 weeks, none of the 20 irradiated patients showed any progression of the developing or already manifest ossification; thus mobilisation and rehabilitation could be carried out as desired. No side effects occurred. The preliminary results of the present study suggest that radiotherapy is an effective local treatment with minimal side effects for the prevention of heterotopic bone formation in patients with paraplegia. (orig.)

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

    DEFF Research Database (Denmark)

    Chen, Li; Shi, Kaikai; Frary, Charles Edward;

    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...

  1. Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation.

    Science.gov (United States)

    Yun, Hyung-Mun; Ahn, Su-Jin; Park, Kyung-Ran; Kim, Mi-Joo; Kim, Jung-Ju; Jin, Guang-Zhen; Kim, Hae-Won; Kim, Eun-Cheol

    2016-04-01

    Magnetism has recently been implicated to play significant roles in the regulation of cell responses. Allowing cells to experience a magnetic field applied externally or scaffolding them in a material with intrinsic magnetic properties has been a possible way of utilizing magnetism. Here we aim to investigate the combined effects of the external static magnetic field (SMF) with magnetic nanocomposite scaffold made of polycaprolactone/magnetic nanoparticles on the osteoblastic functions and bone formation. The SMF synergized with the magnetic scaffolds in the osteoblastic differentiation of primary mouse calvarium osteoblasts, including the expression of bone-associated genes (Runx2 and Osterix) and alkaline phosphatase activity. The synergism was demonstrated in the activation of integrin signaling pathways, such as focal adhesion kinase, paxillin, RhoA, mitogen-activated protein kinase, and nuclear factor-kappaB, as well as in the up-regulation of bone morphogenetic protein-2 and phosphorylation of Smad1/5/8. Furthermore, the SMF/magnetic scaffold-stimulated osteoblasts promoted the angiogenic responses of endothelial cells, including the expression of vascular endothelial growth factor and angiogenin-1 genes and the formation of capillary tubes. When the magnetic scaffolds were implanted in mouse calvarium defects, the application of SMF significantly enhanced the new bone formation at 6 weeks, as revealed by the histological and micro-computed tomographic analyses. Current findings suggest that the combinatory application of external (SMF) and internal (scaffold) magnetism can be a promising tool to regenerative engineering of bone. PMID:26854394

  2. In Vivo Static Creep Loading of the Rat Forelimb Reduces Ulnar Structural Properties at Time-Zero and Induces Damage-Dependent Woven Bone Formation

    OpenAIRE

    Lynch, Jennifer A.; Silva, Matthew J.

    2008-01-01

    Periosteal woven bone forms in response to stress fractures and pathological overload. The mechanical factors that regulate woven bone formation are poorly understood. Fatigue loading of the rat ulna triggers a woven bone response in proportion to the level of applied fatigue displacement. However, because fatigue produces damage by application of cyclic loading it is unclear if the osteogenic response is due to bone damage (injury response) or dynamic strain (adaptive response). Creep loadin...

  3. Bone-like apatite formation on HA/316L stainless steel composite surface in simulated body fluid

    Institute of Scientific and Technical Information of China (English)

    FAN Xin; CHEN Jian; ZOU Jian-peng; WAN Qian; ZHOU Zhong-cheng; RUAN Jian-ming

    2009-01-01

    HA/316L stainless steel(316L SS) biocomposites were prepared by hot-pressing technique. The formation of bone-like apatite on the biocomposite surfaces in simulated body fluid(SBF) was analyzed by digital pH meter, plasma emission spectrometer, scanning electron microscope(SEM) and energy dispersive X-ray energy spectrometer(EDX). The results indicate that the pH value in SBF varies slightly during the immersion. It is a dynamic process of dissolution-precipitation for the formation of apatite on the surface. With prolonging immersion time, Ca and P ion concentrations increase gradually, and then approach equilibrium. The bone-like apatite layer forms on the composites surface, which possesses benign bioactivity and favorable biocompatibility and achieves osseointegration, and can provide firm fixation between HA60/316L SS composite implants and human body bone.

  4. Collagen immobilization of multi-layered BCP-ZrO2 bone substitutes to enhance bone formation

    International Nuclear Information System (INIS)

    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-ZrO2. - Abstract: 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

  5. 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.

  6. Ectopic bone formation cannot occur by hydroxyapatite/β-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

    International Nuclear Information System (INIS)

    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

  7. 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

  8. Long-Term Symptoms Onset and Heterotopic Bone Formation around a Total Temporomandibular Joint Prosthesis: a Case Report

    Directory of Open Access Journals (Sweden)

    Luca Guarda-Nardini

    2014-04-01

    Full Text Available Background: The literature on total alloplastic temporomandibular joint (TMJ reconstructions is encouraging, and studies on total alloplastic TMJ replacements outcomes showed acceptable improvements in terms of both pain levels and jaw function. Nevertheless, some adverse events, such as heterotopic bone formation around the implanted prosthesis, may occur. In consideration of that, the present manuscript describes a case of heterotopic bone formation around a total temporomandibular joint prosthesis, which occurred several years after the implant. Methods: The present manuscript describes a case of heterotopic bone formation around a total TMJ prosthesis, which occurred several years after the implant in patients, who previously underwent multiple failed TMJ surgeries. Results: Ten years after the surgical TMJ replacement to solve an ankylotic bone block, the patient came to our attention again referring a progressive limitation in mouth opening. A computerized tomography showed evidence of marked heterotopic bone formation in the medial aspects of the joint, where a new-born ankylotic block occupied most part of the gap created by resecting the coronoid process at the time of the TMJ prosthesis insertion. Conclusions: Despite this adverse event has been sometimes described in the literature, this is the first case in which its occurrence happened several years after the temporomandibular joint replacement. It can be suggested that an accurate assessment of pre-operative risk factors for re-ankylosis (e.g., patients with multiple failed temporomandibular joint surgeries and within-intervention prevention (e.g., strategies to keep the bone interfaces around the implant separated should be better standardized and define in future studies.

  9. Monotropein isolated from the roots of Morinda officinalis increases osteoblastic bone formation and prevents bone loss in ovariectomized mice.

    Science.gov (United States)

    Zhang, Zhiguo; Zhang, Qiaoyan; Yang, Hua; Liu, Wei; Zhang, Naidan; Qin, Luping; Xin, Hailiang

    2016-04-01

    Monotropein is a natural iridoid glycoside enriched in Morinda officinalis and has been used for medicinal purposes in China. In the present study, we systematically examined its effects on ovariectomy (OVX)-induced osteoporosis in mice and osteoblastic MC3T3-E1 cells for the first time. Eight-week-old female C57/BL6 mice were used to evaluate the osteoprotective effect of monotropein. Results showed that administration of monotropein (40 or 80mg/kg/day) for four weeks exerted good bone protective effects as evidenced by the increase of bone mineral content (BMC), bone mineral density (BMD), bone volume fraction (BVF) and improvement of bone microstructure. Monotropein also enhanced the parameters of biomechanical properties, including maximum load, maximum stress and elastic modulus of femur in OVX mice. In addition, monotropein treatment decreased the serum levels of interleukin 1 (IL-1), interleukin 6 (IL-6) and soluble receptor activator of NF-κB ligand (sRANKL) in OVX mice. In this study, we also assessed the effects of monotropein on the proliferation and differentiation of osteoblastic MC3T3-E1 cells in vitro. After incubation for 48h, the cell proliferation was increased at the concentration of 10μM, 25μM, 50μM and 100μM. ALP activities were significantly increased after treatment with monotropein for 72h. Quantitative analyses with alizarin red staining showed significantly increased mineralization of MC3T3-E1 cells after treatment with monotropein for 28days. Based on these results, monotropein may serve as a new candidate or a leading compound for antiosteoporosis. PMID:26996879

  10. Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

    DEFF Research Database (Denmark)

    Jensen, Simon S; Chen, B; Bornstein, Michael M; Bosshardt, Dieter D; Buser, Daniel

    2011-01-01

    Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole or...

  11. In vitro and in vivo evaluation of bone formation using solid freeform fabrication-based bone morphogenic protein-2 releasing PCL/PLGA scaffolds

    International Nuclear Information System (INIS)

    The aim of this study was to develop novel polycaprolactone/poly(lactic-co-glycolic acid) (PCL/PLGA) scaffolds with a heparin–dopamine (Hep–DOPA) conjugate for controlled release of bone morphogenic protein-2 (BMP-2) to enhance osteoblast activity in vitro and also bone formation in vivo. PCL/PLGA scaffolds were prepared by a solid freeform fabrication method. The PCL/PLGA scaffolds were functionalized with Hep–DOPA and then BMP-2 was sequentially coated onto the Hep–DOPA/PCL/PLGA scaffolds. The characterization and surface elemental composition of all scaffolds were evaluated by scanning electron microscope and x-ray photoelectron spectroscopy. The osteoblast activities on all scaffolds were assessed by cell proliferation, alkaline phosphatase (ALP) activity and calcium deposition in vitro. To demonstrate bone formation in vivo, plain radiograph, micro-computed tomography (micro-CT) evaluation and histological studies were performed after the implantation of all scaffolds on a rat femur defect. Hep–DOPA/PCL/PLGA had more controlled release of BMP-2, which was quantified by enzyme-linked immunosorbent assay, compared with Hep/PCL/PLGA. The in vitro results showed that osteoblast-like cells (MG-63 cells) grown on BMP-2/Hep–DOPA/PCL/PLGA had significantly enhanced ALP activity and calcium deposition compared with those on BMP-2/Hep/PCL/PLGA and PCL/PLGA. In addition, the plain radiograph, micro-CT evaluation and histological studies demonstrated that the implanted BMP-2/Hep–DOPA/PCL/PLGA on rat femur had more bone formation than BMP-2/Hep/PCL/PLGA and PCL/PLGA in vivo. (paper)

  12. Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/β-catenin signaling pathway in vivo and in vitro

    OpenAIRE

    Junhua Wang; Yunxia Tao; Zichuan Ping; Wen Zhang; Xuanyang Hu; Yijun Wang; Liangliang Wang; Jiawei Shi; Xiexing Wu; Huilin Yang; Yaozeng Xu; Dechun Geng

    2016-01-01

    Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Her...

  13. Zinc may increase bone formation through stimulating cell proliferation, alkaline phosphatase activity and collagen synthesis in osteoblastic MC3T3-E1 cells

    OpenAIRE

    Seo, Hyun-Ju; Cho, Young-Eun; Kim, Taewan; Shin, Hong-In; Kwun, In-Sook

    2010-01-01

    Zinc is an essential trace element required for bone formation, however not much has been clarified yet for its role in osteoblast. We hypothesized that zinc would increase osteogenetic function in osteoblasts. To test this, we investigated whether zinc treatment enhances bone formation by stimulating osteoblast proliferation, bone marker protein alkaline phosphatase activity and collagen synthesis in osteoblastic MC3T3-E1 cells. MC3T3-E1 cells were cultured and treated with various concentra...

  14. MURINE MOBILIZED PERIPHERAL BLOOD STEM CELLS HAVE A LOWER CAPACITY THAN BONE MARROW TO INDUCE MIXED CHIMERISM AND TOLERANCE

    OpenAIRE

    Koporc, Zvonimir; Pilat, Nina; Nierlich, Patrick; Blaha, Peter; Bigenzahn, Sinda; Pree, Ines; Selzer, Edgar; Sykes, Megan; Muehlbacher, Ferdinand; Wekerle, Thomas

    2008-01-01

    Allogeneic bone marrow transplantation (BMT) under costimulation blockade allows induction of mixed chimerism and tolerance without global T cell depletion. The mildest such protocols without recipient cytoreduction, however, require clinically impracticable bone marrow (BM) doses. The successful use of mobilized peripheral blood stem cells (PBSC) instead of BM in such regimens would provide a substantial advance, allowing transplantation of higher doses of hematopoietic donor cells. We thus ...

  15. Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation

    OpenAIRE

    N C Rivron; Raiss, C.C.; Liu, J.; Nandakumar, A.; Sticht, C; Gretz, N; Truckenmuller, R.K.; Rouwkema, J.; Blitterswijk, van, W.J.

    2012-01-01

    Large bone defects naturally regenerate via a highly vascularized tissue which progressively remodels into cartilage and bone. Current approaches in bone tissue engineering are restricted by delayed vascularization and fail to recapitulate this stepwise differentiation toward bone tissue. Here, we use the morphogen Sonic Hedgehog (Shh) to induce the in vitro organization of an endothelial capillary network in an artificial tissue. We show that endogenous Hedgehog activity regulates angiogenic...

  16. Use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement

    Energy Technology Data Exchange (ETDEWEB)

    Sylvester, J.E.; Greenberg, P.; Selch, M.T.; Thomas, B.J.; Amstutz, H.

    1988-03-01

    Formation of heterotopic bone (HTB) following total hip replacement may partially or completely ankylose the joint space, causing pain and/or limiting the range of motion. Patients at high risk for formation of HTB postoperatively include those with previous HTB formation, heterotopic osteoarthritis, and active rheumatoid spondylitis. Patients in these high risk groups have a 63-69% incidence of post-operative HTB formation, usually seen radiographically by 2 months post-operation. From 1980-1986 twenty-nine hips in 28 consecutively treated patients were irradiated post-operatively at the UCLA Center for the Health Sciences. The indication for irradiation was documented HTB formation previously in 26 of the 27 hips presented below. From 1980-1982 patients received 20 Gray (Gy) in 2 Gy fractions; from 1982-1986 the dose was reduced to 10 Gy in 2 Gy fractions. Twenty-seven hips in 26 patients completed therapy and were available for evaluation, with a minimum of 2 month follow-up, and a median follow-up of 12 months. Three of 27 hips developed significant HTB (Brooker grade III or IV) post-operatively, whereas 5 of 27 hips developed minor, nonsymptomatic HTB (Brooker grade I). When irradiation was begun by postoperative day 4, 0 of 17 hips formed significant HTB. If irradiation began after post-operative day 4, 3 of 10 hips formed significant HTB (Brooker grade III or IV). These 3 hips received doses of 10 Gy in one hip and 20 Gy in the other 2 hips. There were no differences in the incidence or severity of side effects in the 10 Gy vs. the 20 Gy treatment groups. Eighteen hips received 10 Gy, 8 hips 20 Gy and, 1 hip 12 Gy. In conclusion, 10 Gy in 5 fractions appears as effective as 20 Gy in 10 fractions at preventing post-operative formation of HTB. For optimal results, treatment should begin as early as possible prior to post-operative day 4.

  17. Skeletal Self-Repair: Stress Fracture Healing by Rapid Formation and Densification of Woven Bone

    OpenAIRE

    Uthgenannt, Brian A.; Kramer, Michael H.; Hwu, Joyce A.; Wopenka, Brigitte; Silva, Matthew J.

    2007-01-01

    Stress fractures of varying severity were created using a rat model of skeletal fatigue loading. Periosteal woven bone formed in proportion to the level of bone damage, resulting in the rapid recovery of whole-bone strength independent of stress fracture severity.

  18. Strong Price of Anarchy of Coalition Formation Game with Fair Cost Sharing and Bounded Capacity for Sharing Economy

    OpenAIRE

    Chau, Chi-Kin; Elbassioni, Khaled

    2015-01-01

    This paper studies a coalition formation game subject to the capacity of $K$ participants per coalition. The participants in each coalition are supposed to split the associated cost according to a given cost sharing solution. A stable coalition structure is established, when no group of participants can opt out to form another coalition that leads to lower individual payments. We investigate the strong price of anarchy (PoA) comparing a worst-case stable coalition structure and a social optim...

  19. Structural Determinants of the Capacity of Heparin to Inhibit the Formation of the Human Amplification C3 Convertase

    OpenAIRE

    Kazatchkine, Michel D.; Fearon, Douglas T.; Metcalfe, Dean D.; Rosenberg, Robert D.; Austen, K. Frank

    1981-01-01

    The ability of heparin glycosaminoglycan to prevent formation of the properdin-stabilized amplification C3 convertase is independent of antithrombin binding activity and requires substitution of the amino sugar and a degree of oxygen (O)-sulfation which could be on the uronic acid or the amino sugar. Preparations of heparin glycosaminoglycan isolated by different techniques from different species (rat, human, and porcine) exhibited an equivalent capacity to inhibit generation of the amplifica...

  20. 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.

  1. 1,25-Dihydroxyvitamin D3 prevents bone loss of the secondary spongiosa in arthritic rats by an increase of bone formation and mineralization and inhibition of bone resorption

    OpenAIRE

    Oelzner, Peter; Petrow, Peter K; Wolf, Gunter; Bräuer, Rolf

    2014-01-01

    Background Active vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment. However, because the direct effects of 1,25-dihydroxyvitamin D3 (1,25(OH) 2D3) on bone formation and resorption are very complex, the net effect of 1,25(OH)2D3 on histomorphometric parameters of bone turnover and mineralisation should be investigated. Therefore, we examined the influence of 1,25(OH)2D3 therapy on arthritis-induced alteratio...

  2. Bone formation and degradation behavior of nanocrystalline hydroxyapatite with or without collagen-type 1 in osteoporotic bone defects - an experimental study in osteoporotic goats.

    Science.gov (United States)

    Alt, Volker; Cheung, Wing Hoi; Chow, Simon K H; Thormann, Ulrich; Cheung, Edmond N M; Lips, Katrin S; Schnettler, Reinhard; Leung, Kwok-Sui

    2016-06-01

    The intention of the current work is to assess new bone formation and degradation behavior of nanocrystalline hydroxyapatite with (HA/col-1) or without collagen-type I (HA) in osteoporotic metaphyseal bone defects in goats. After ovariectomy and special low-calcium diet for three months, 3 drill hole defects in the vertebrae of L3, L4, L5, 4 drill hole defects in the right and left iliac crest and 1 drill hole defect at the distal femur were created in three Chinese mountain goats with a total of 24 defects. The defects were either filled with one of the biomaterials or left empty (empty defect control group). After 42 days, the animals were euthanized and the samples were assessed for new bone formation using high-resolution peripheral quantitative computed tomography (HR-pQCT) and histomorphometry with 2 regions of interest. Detail histology, enzymehistochemistry and immunohistochemistry as well as connexin-43 in situ hybridization and transmission electron microscopy were carried out for evaluation of degradation behavior of the materials and cellular responses of the surrounding tissue in respect to the implants. HR-pQCT showed the highest BV/TV ratio (p = 0.008) and smallest trabecular spacing (p = 0.005) for HA compared to the other groups in the region of interest at the interface with 1mm distance to the initially created defect. The HA/col-1 yielded the highest connectivity density (Conn.D) (p = 0.034) and the highest number of trabeculae (Tb.N) (p = 0.002) compared to the HA and the control group. Histomorphometric analysis for the core region of the initially created defect revealed a statistically higher new bone formation in the HA (p = 0.001) and HA/col-1 group (p = 0.001) compared to the empty defect group including all defect sites. This result was confirmed for site specific analysis with significant higher new bone formation for the HA group for vertebral defects compared to the empty defect group (p = 0.029). For the interface region, no

  3. 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

    had a complete absence of osteoid surfaces, and a 5-fold increase in the extent of eroded/reversal surfaces after 7months. Most of these reversal surfaces were actually arrested reversal surfaces, defined as reversal surfaces without the presence of neighbouring osteoid surfaces or osteoclasts, which...... is classically observed next to active reversal surfaces. As in humans, these arrested reversal surfaces had compared to active reversal surfaces a reduced canopy coverage, a significantly decreased cell density, and a decreased immunoreactivity for the osteoblastic markers osterix, runx2 and smooth...... muscle actin 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...

  4. SP600125 enhances the anti-apoptotic capacity and migration of bone marrow mesenchymal stem cells treated with tumor necrosis factor-α.

    Science.gov (United States)

    Wei, Bo; Bai, Xizhuang; Chen, Kang; Zhang, Xiaonan

    2016-07-01

    Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic disorders associated with inflammation of joints characterized by damage to the underlying cartilage and bone. Bone marrow mesenchymal stem cells (BMSCs) are candidates for regeneration of bone and cartilage, which is inhibited by inflammatory cytokines in OA and RA, in particular tumor necrosis factor-α (TNF-α). This study aimed to investigate if the c-Jun N-terminal kinases (JNK)-specific inhibitor SP600125 could enhance the anti-apoptosis and migration of BMSCs treated with TNF-α. The level of apoptosis was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)/4',6-diamidino-2-phenylindole (DAPI) staining, annexin V/propidium iodide (PI) staining and western blotting. Migration of BMSCs was assessed using transwell migration chambers. We showed that the survival capacity and migration of BMSCs was significantly inhibited by TNF-α, which was blocked by pretreatment with SP600125. In the presence of SP600125, expression of cleaved caspase-9/-3 and p53 as well as the ratio of Bax to Bcl-2 was significantly decreased compared to treatment with TNF-α alone. Our results therefore indicate that SP600125 improves the migration capacity of TNF-α-treated BMSCs and exerts a significant effect on the viability of TNF-α-treated BMSCs through reducing the up-regulation of p53, caspase-9/-3 and the Bcl-2 family induced by TNF-α. These findings suggest that SP600125 is of potential use in promoting the regeneration of bone and cartilage in OA and RA. PMID:27233606

  5. Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/β-catenin signaling pathway in vivo and in vitro.

    Science.gov (United States)

    Wang, Junhua; Tao, Yunxia; Ping, Zichuan; Zhang, Wen; Hu, Xuanyang; Wang, Yijun; Wang, Liangliang; Shi, Jiawei; Wu, Xiexing; Yang, Huilin; Xu, Yaozeng; Geng, Dechun

    2016-01-01

    Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs). Additionally, icariin increased bone mass and decreased bone loss in titanium-particle-induced osteolytic sites. Mechanistically, icariin inhibited decreased β-catenin stability induced by titanium particles in vivo and in vitro. To confirm icariin mediated its bone-protective effects via the Wnt/β-catenin signaling pathway, we demonstrated that ICG-001, a selective Wnt/β-catenin inhibitor, attenuated the effects of icariin on MSC mineralization in vitro and bone formation in vivo. Therefore, icariin could induce osteogenic differentiation of MSCs and promote new bone formation at a titanium-particle-induced osteolytic site via activation of the Wnt/β-catenin signaling pathway. These results further support the protective effects of icariin on particle-induced bone loss and provide novel mechanistic insights into the recognized bone-anabolic effects of icariin and an evidence-based rationale for its use in PIO treatment. PMID:27029606

  6. Study of bone formation in the mandibular alveolar process of the young adult beagle by tetracycline label analysis

    International Nuclear Information System (INIS)

    The mandibular alveolar processes of young, adult beagles were observed to determine several aspects of tissue-level bone turnover. The animals had been previously labeled with a double tetracycline (TC) regimen, and analysis carried out on the resulting label distributions and patterns. Analysis of the fraction of bone surface incorporating TC showed that about 1.5 percent of surfaces are double labeled, 16 percent are single labeled, and 75 percent of surfaces are bare of label. The apposition rate for formation sites was found to be approximately 1.54 μm/day

  7. Angiogenic factor-enriched platelet-rich plasma enhances in vivo bone formation around alloplastic graft material

    OpenAIRE

    Kim, Eun-Seok; Kim, Jae-Jin; Park, Eun-Jin

    2010-01-01

    PURPOSE Although most researchers agree that platelet-rich plasma (PRP) is a good source of autogenous growth factors, its effect on bone regeneration is still controversial. The purpose of this study was to evaluate whether increasing angiogenic factors in the human PRP to enhance new bone formation through rapid angiogenesis. MATERIAL AND METHODS In vitro, the human platelets were activated with application of shear stress, 20 µg/ml collagen, 2 mM CaCl2 and 10U thrombin/1 × 109 platelets. L...

  8. EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; KerryAtkinson

    1994-01-01

    We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo.IL-4 alone was found to be incapable of stimulating colony formation,but it inhibited both IL-3-and GM-CSF-induced colony for-mation by murine hematopoietic progenitor cells.In contrast,colony formation induced by G-CSF was enhanced in the presence of IL-4.We also studied the influence of IL-4 on hematopoietie reconstiution after allogeneic bone marrow transplantation in a murine model,and found that IL-4 and G-CSF was significantly suppressed by IL-4.The combination of IL-4 and GM-CSF caused a significant decrease in the absolute mumber of meutrophils.

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

    OpenAIRE

    Hasani-Ranjbar Shirin; Jouyandeh Zahra; Qorbani Mostafa; Hemmatabadi Mahbubeh; Larijani Bagher

    2012-01-01

    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 diff...

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

    OpenAIRE

    Shirin Hasani-Ranjbar; Zahra Jouyandeh; Mostafa Qorbani; Mahbubeh Hemmatabadi; Bagher Larijani

    2012-01-01

    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 org...

  11. 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

  12. 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

  13. Influence of interferon preparations on the proliferative capacity of human and mouse bone marrow cells in vitro

    NARCIS (Netherlands)

    E. van 't Hull (Eveline); B. Löwenberg (Bob); M. de Vries (Marco); H. Schellekens (Huub)

    1978-01-01

    textabstractThe toxicity of interferon to bone marrow was studied by the use of in vitro colony forming assays for hemopoietic cells. In the same study the relative inhibitory effects of two clinically common interferon preparations, leukocyte and fibroblast interferons, were compared with regard to

  14. R-Spondin 1 promotes vibration-induced bone formation in mouse models of osteoporosis

    OpenAIRE

    Wang, Haitao; Brennan, Tracy A.; Russell, Elizabeth; Kim, Jung-Hoon; Egan, Kevin P.; Chen, Qijun; Israelite, Craig; Schultz, David C.; Johnson, Frederick B.; Pignolo, Robert J.

    2013-01-01

    Bone tissue adapts to its functional environment by optimizing its morphology for mechanical demand. Among the mechanosensitive cells that recognize and respond to forces in the skeleton are osteocytes, osteoblasts, and mesenchymal progenitor cells (MPCs). Therefore, the ability to use mechanical signals to improve bone health through exercise and devices that deliver mechanical signals is an attractive approach to age-related bone loss; however, the extracellular or circulating mediators of ...

  15. ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

    OpenAIRE

    Mourskaia, Anna A; Amir, Eitan; Dong, Zhifeng; Tiedemann, Kerstin; Cory, Sean; Omeroglu, Atilla; Bertos, Nicholas; Ouellet, Véronique; Clemons, Mark; Scheffer, George L.; Park, Morag; Hallett, Michael; Svetlana V Komarova; Siegel, Peter M.

    2012-01-01

    Introduction Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture micr...

  16. Analyzing Heat Capacity Profiles of Peptide-Containing Membranes: Cluster Formation of Gramicidin A

    OpenAIRE

    Ivanova, V.; Makarov, I.; Schaeffer, T.; Heimburg, T.

    2003-01-01

    The analysis of peptide and protein partitioning in lipid membranes is of high relevance for the understanding of biomembrane function. We used statistical thermodynamics analysis to demonstrate the effect of peptide mixing behavior on heat capacity profiles of lipid membranes with the aim to predict peptide aggregation from cP-profiles. This analysis was applied to interpret calorimetric data on the interaction of the antibiotic peptide gramicidin A with lipid membranes. The shape of the hea...

  17. Divergent resorbability and effects on osteoclast formation of commonly used bone substitutes in a human in vitro-assay.

    Directory of Open Access Journals (Sweden)

    Johannes Keller

    Full Text Available Bioactive bone substitute materials are a valuable alternative to autologous bone transplantations in the repair of skeletal defects. However, clinical studies have reported varying success rates for many commonly used biomaterials. While osteoblasts have traditionally been regarded as key players mediating osseointegration, increasing evidence suggests that bone-resorbing osteoclasts are of crucial importance for the longevity of applied biomaterials. As no standardized data on the resorbability of biomaterials exists, we applied an in vitro-assay to compare ten commonly used bone substitutes. Human peripheral blood mononuclear cells (PBMCs were differentiated into osteoclasts in the co-presence of dentin chips and biomaterials or dentin alone (control for a period of 28 days. Osteoclast maturation was monitored on day 0 and 14 by light microscopy, and material-dependent changes in extracellular pH were assessed twice weekly. Mature osteoclasts were quantified using TRAP stainings on day 28 and their resorptive activity was determined on dentin (toluidin blue staining and biomaterials (scanning electron microscopy, SEM. The analyzed biomaterials caused specific changes in the pH, which were correlated with osteoclast multinuclearity (r = 0.942; p = 0.034 and activity on biomaterials (r = 0.594; p = 0.041. Perossal led to a significant reduction of pH, nuclei per osteoclast and dentin resorption, whereas Tutogen bovine and Tutobone human strikingly increased all three parameters. Furthermore, natural biomaterials were resorbed more rapidly than synthetic biomaterials leading to differential relative resorption coefficients, which indicate whether bone substitutes lead to a balanced resorption or preferential resorption of either the biomaterial or the surrounding bone. Taken together, this study for the first time compares the effects of widely used biomaterials on osteoclast formation and resorbability in an unbiased approach that may now aid

  18. 兔股骨节段缺损模型研究磷酸钙骨水泥骨愈合性能%Bone Healing Capacity of Calcium Phosphate Cement Cylinder in a Rabbit Femur Segmental Defect Model

    Institute of Scientific and Technical Information of China (English)

    王大伟; 潘朝晖; 赵玉祥; 栾兆新

    2015-01-01

    Objective:To investigate the bone healing capacity of calcium phosphate cement ( CPC) cylinder in a rabbit femur seg-mental defect model by comparing the influence of muscle or periosteum as wrapping material.Methods: Pre-hardened CPC cylinder was prepared.Three specimens were analyzed by scanning electron microscopy and X-ray diffraction to characterize its microstructure and chemical composition.Sixty adult rabbits were randomly assigned to four groups,then received a defect size of 15 mm osteotomy within the femurs.The 8-hole plate was fixed with three screws in the proximal and distal part of the defect, respectively.In group A, the fem-oral defects were left alone;in group B, the defects with retained periosteum; in group C, the defects were grafted with CPC cylinder wrapped by muscle;and in group D, the defects were grafted with CPC cylinder wrapped by periosteum.Five rabbits from each group were sacrificed at 4, 8 and 12 weeks postoperatively.The samples were evaluated with radiological, biomechanical and histological meth-ods.Results:Irregular particles were seen on the surface of specimens, the pore size was approximately 10 μm.The peak locations for the hydroxyapatite were seen in the X-ray diffraction patterns of the specimens.Group A showed a few radiographic evidence of new bone formation within the boundary of the defect at 4 weeks.Three bone defects bridged at 8 weeks and 4 bone defects bridged at 12 weeks. Group B showed radiographic evidence of new bone formation at 4 weeks.Four bone defects bridged at 8 weeks and 5 bone defects bridged at 12 weeks.Group C showed discernable interface between the CPC cylinder and both femoral cut ends at 4 weeks, which became invisi-ble at 8 weeks.Defects bridged by continuous callus beside the CPC cylinder in 4 rabbits and completely surrounded in 1 rabbit at 12 weeks.Group D showed better quality of new bone formation, the CPC cylinders were surrounded by new bone at 12 weeks.However, all CPCs retained their

  19. Administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma-induced nerve sprouting, neuroma formation and bone cancer pain

    Directory of Open Access Journals (Sweden)

    Bloom Aaron P

    2010-12-01

    Full Text Available Abstract Pain often accompanies cancer and most current therapies for treating cancer pain have significant unwanted side effects. Targeting nerve growth factor (NGF or its cognate receptor tropomyosin receptor kinase A (TrkA has become an attractive target for attenuating chronic pain. In the present report, we use a mouse model of bone cancer pain and examine whether oral administration of a selective small molecule Trk inhibitor (ARRY-470, which blocks TrkA, TrkB and TrkC kinase activity at low nm concentrations has a significant effect on cancer-induced pain behaviors, tumor-induced remodeling of sensory nerve fibers, tumor growth and tumor-induced bone remodeling. Early/sustained (initiated day 6 post cancer cell injection, but not late/acute (initiated day 18 post cancer cell injection administration of ARRY-470 markedly attenuated bone cancer pain and significantly blocked the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor bearing bone, but did not have a significant effect on tumor growth or bone remodeling. These data suggest that, like therapies that target the cancer itself, the earlier that the blockade of TrkA occurs, the more effective the control of cancer pain and the tumor-induced remodeling of sensory nerve fibers. Developing targeted therapies that relieve cancer pain without the side effects of current analgesics has the potential to significantly improve the quality of life and functional status of cancer patients.

  20. 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.

  1. Radiographic Assessment of Bone Formation Using rhBMP2 at Maxillary Periapical Surgical Defects: A Case Series.

    Science.gov (United States)

    Kumar, M Siva; Kumar, M Hari; Vishalakshi, K; Sabitha, H

    2016-04-01

    Periapical cysts are the most common inflammatory odontogenic cysts arising from untreated dental caries with pulp necrosis and periapical infection. The choice of treatment is often influenced by various factors like size, extension of the lesion, proximity to vital structures, systemic condition and compliance of the patient too. The treatment protocol for management of periapical cysts is still under discussion and options vary from conservative treatment by means of endodontic technique to surgical treatment like decompression or a marsupialisation or even to enucleation. Large bony defect secondary to periapical surgery compromising the tooth integrity often requires bone graft to enhance bone formation and thus restoring function at the earliest. The present case series included 10 patients who had established periapical pathology secondary to history of trauma on upper anterior teeth as well patients with history of carious teeth with an apparent failure in root canal therapy. All ten patients were treated with cyst enucleation and apiceotomy along with 1.4cc Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge implantation at surgical defect. Radiographs and clinical examinations were done upto 3 months to evaluate healing. Radiographic and clinical assessments revealed bone regeneration and restoration of the maxillary surgical defects in all 10 patients. No evidence of graft failure was noted. The Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge carrier is thus proved to be a viable option for the treatment of maxillary periapical surgical defects. PMID:27190972

  2. Radiographic Assessment of Bone Formation Using rhBMP2 at Maxillary Periapical Surgical Defects: A Case Series

    Science.gov (United States)

    Kumar, M. Hari; Vishalakshi, K.; Sabitha, H.

    2016-01-01

    Periapical cysts are the most common inflammatory odontogenic cysts arising from untreated dental caries with pulp necrosis and periapical infection. The choice of treatment is often influenced by various factors like size, extension of the lesion, proximity to vital structures, systemic condition and compliance of the patient too. The treatment protocol for management of periapical cysts is still under discussion and options vary from conservative treatment by means of endodontic technique to surgical treatment like decompression or a marsupialisation or even to enucleation. Large bony defect secondary to periapical surgery compromising the tooth integrity often requires bone graft to enhance bone formation and thus restoring function at the earliest. The present case series included 10 patients who had established periapical pathology secondary to history of trauma on upper anterior teeth as well patients with history of carious teeth with an apparent failure in root canal therapy. All ten patients were treated with cyst enucleation and apiceotomy along with 1.4cc Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge implantation at surgical defect. Radiographs and clinical examinations were done upto 3 months to evaluate healing. Radiographic and clinical assessments revealed bone regeneration and restoration of the maxillary surgical defects in all 10 patients. No evidence of graft failure was noted. The Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge carrier is thus proved to be a viable option for the treatment of maxillary periapical surgical defects. PMID:27190972

  3. 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. PMID:27040245

  4. 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; Ditzel, Nicholas; Shi, Kaikai; Hokland, Lea; Kassem, Moustapha

    2014-01-01

    target 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...... regulatory effects controlling both hMSC proliferation and OB differentiation. Tissue-specific inhibition of miR-34a might be a potential novel therapeutic strategy for enhancing in vivo bone formation. Stem Cells 2014;32:902-912......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...

  5. A method for quick assessment of CO2 storage capacity in closedand semi-closed saline formations

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Q.; Birkholzer, J.; Tsang, C.F.; Rutqvist, J.

    2008-02-10

    Saline aquifers of high permeability bounded by overlying/underlying seals may be surrounded laterally by low-permeability zones, possibly caused by natural heterogeneity and/or faulting. Carbon dioxide (CO{sub 2}) injection into and storage in such 'closed' systems with impervious seals, or 'semi-closed' systems with nonideal (low-permeability) seals, is different from that in 'open' systems, from which the displaced brine can easily escape laterally. In closed or semi-closed systems, the pressure buildup caused by continuous industrial-scale CO{sub 2} injection may have a limiting effect on CO{sub 2} storage capacity, because geomechanical damage caused by overpressure needs to be avoided. In this research, a simple analytical method was developed for the quick assessment of the CO{sub 2} storage capacity in such closed and semi-closed systems. This quick-assessment method is based on the fact that native brine (of an equivalent volume) displaced by the cumulative injected CO{sub 2} occupies additional pore volume within the storage formation and the seals, provided by pore and brine compressibility in response to pressure buildup. With nonideal seals, brine may also leak through the seals into overlying/underlying formations. The quick-assessment method calculates these brine displacement contributions in response to an estimated average pressure buildup in the storage reservoir. The CO{sub 2} storage capacity and the transient domain-averaged pressure buildup estimated through the quick-assessment method were compared with the 'true' values obtained using detailed numerical simulations of CO{sub 2} and brine transport in a two-dimensional radial system. The good agreement indicates that the proposed method can produce reasonable approximations for storage-formation-seal systems of various geometric and hydrogeological properties.

  6. Induction of DNA-strand breaks after X- irradiation in murine bone cells of various differentiation capacities

    Science.gov (United States)

    Lau, P.; Hellweg, C. E.; Kirchner, S.; Arenz, A.; Baumstark-Khan, C.; Horneck, G.

    Bone loss resulting from long-duration space flight is a well known medical risk for space travellers, as a weakened skeleton is more susceptible to bone fractures. In addition to weightlessness the astronaut is also exposed to cosmic ionizing radiation. In order to elucidate changes in bone cell metabolism by ionizing radiation, a ground-based bone cell model has been developed. This model consists of a bunch of immortalized murine osteocyte, osteoblast and pre-osteoblast cell lines representing discrete stages of differentiation: The osteocyte cell line MLO-Y4 (obtained from L. Bonewald, Kansas City, USA), the osteoblast cell line OCT-1 (obtained from D. Chen, San Antonio, USA), and the subclones 4 and 24 of the osteoblast cell line MC3T3-E1 (obtained from ATCC, Manassas, Virginia, USA). Regarding their growth properties, MLO-Y4 cells show the highest growth velocity with a doubling time of 15.8 h. The osteoblast cell line OCT-1 has a doubling time of 27.3 h. The respective values for MC3T3-E1 subclone 24 and S4 are 90.5 h and 51.6 h. To investigate the stage of differentiation, the expression of alkaline phosphatase, of osteocalcin and of E11 was examined. Survival after X-ray exposure was determined using the colony forming ability test. The resulting dose-effect relationships revealed significant differences. The parameter D0 of the survival curves ranges between 1.8 Gy for OCT-1, 1.9 Gy for MLO-Y4, 2.0 Gy for subclone 24 and 2,3 Gy for subclone 4. The quantitative acquisition of DNA-strand breaks was performed by Fluorescent Analysis of DNA-Unwinding (FADU). The results can be correlated with the corresponding survival curve. In conclusion, the cell lines with higher differentiation levels are less sensitive to radiation when compared to the lower differentiated osteoblast cell lines.

  7. The Role of Scaffold Architecture and Composition on the Bone Formation by Adipose-Derived Stem Cells

    OpenAIRE

    Declercq, Heidi A.; Desmet, Tim; Dubruel, Peter; Cornelissen, Maria J.

    2013-01-01

    Scaffold architecture and composition are crucial parameters determining the initial cell spatial distribution and consequently bone tissue formation. Three-dimensional poly-ɛ-caprolactone (PCL) scaffolds with a 0/90° lay-down pattern were plotted and subjected to (1) an oxygen plasma (PCL O) or (2) a postargon plasma modification with gelatin and fibronectin (PCL Fn). These scaffolds with an open pore structure were compared with more compact scaffolds fabricated by conventional processing t...

  8. The role of scaffold architecture and composition on the bone formation by adipose-derived stem cells

    OpenAIRE

    Declercq, Heidi; Desmet, Tim; Dubruel, Peter; Cornelissen, Maria

    2014-01-01

    Scaffold architecture and composition are crucial parameters determining the initial cell spatial distribution and consequently bone tissue formation. Three-dimensional poly-ε-caprolactone (PCL) scaffolds with a 0/90° lay-down pattern were plotted and subjected to 1) an oxygen plasma (PCL O) or 2) a post-argon plasma modification with gelatine and fibronectin (PCL Fn). These scaffolds with an open pore structure were compared with more compact scaffolds fabricated by conventional processing t...

  9. Controlled Release of Simvastatin from In situ Forming Hydrogel Triggers Bone Formation in MC3T3-E1 Cells

    OpenAIRE

    Park, Yoon Shin; David, Allan E.; Park, Kyung Min; Lin, Chia-Ying; Than, Khoi D.; Lee, Kyuri; Park, Jun Beom; Jo, Inho; Park, Ki Dong; Yang, Victor C.

    2012-01-01

    Simvastatin (SIM), a drug commonly administered for the treatment of hypercholesterolemia, has been recently reported to induce bone regeneration/formation. In this study, we investigated the properties of hydrogel composed of gelatin–poly(ethylene glycol)–tyramine (GPT) as an efficient SIM delivery vehicle that can trigger osteogenic differentiation. Sustained delivery of SIM was achieved through its encapsulation in an injectable, biodegradable GPT-hydrogel. Cross-linking of the gelatin-bas...

  10. The comparative effectiveness of demineralized bone matrix, beta-tricalcium phosphate, and bovine-derived anorganic bone matrix on inflammation and bone formation using a paired calvarial defect model in rats

    Directory of Open Access Journals (Sweden)

    Khoshzaban A

    2011-09-01

    Full Text Available Ahad Khoshzaban1,2,3, Shahram Mehrzad1, Vida Tavakoli2, Saeed Heidari Keshel2, Gholam Reza Behrouzi2, Maryam Bashtar2 1Iranian Tissue Bank Research and Preparation Center, Imam Khomeini Hospital Complex, 2Stem Cells Preparation Unit, Eye Research Center, Farabi Hospital, Tehran University of Medical Science, 3Dental Bio Material Department, Tehran University of Medical Science, Faculty of Dentistry, Tehran, Iran Background: In this study, the effectiveness of Iranian Tissue Bank–produced demineralized bone matrix (ITB-DBM, beta-tricalcium phosphate (ßTCP, and Bio-Oss® (Geistlich Pharma AG, Wolhusen, Switzerland were evaluated and compared with double controls. The main goal was to measure the amount of new bone formation in the center of defects created in rat calvaria. Another goal was to compare the controls and evaluate the effects of each treatment material on their adjacent untreated (control defects. Methods: In this study, 40 male Wistar rats were selected and divided into four groups, In each group, there were ten rats with two defects in their calvarias; one of them is considered as control and the other one was treated with ITB-DBM (group 1, BIO-OSS (group2, and ßTCP (group 3, respectively. But in group 4, both defects were considered as control. The amount of inflammation and new bone formation were evaluated at 4 and 10 weeks. In the first group, one defect was filled with ITB-DBM; in the second group, one defect was filled with Bio-Oss; in the third group, one defect was filled with ßTCP; and in the fourth group, both defects were left unfilled. Zeiss microscope (Carl Zeiss AG, Oberkochen, Germany and Image Tool® (version 3.0; University of Texas Health Science Center at San Antonio, San Antonio, TX software were used for evaluation. SPSS Statistics (IBM Corp, Somers, NY was used for statistical analysis. Results: Maximum bone formation at 4 and 10 weeks were observed in the ITB-DBM group (46.960% ± 4.366%, 94.970% ± 0

  11. Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Siersbaek, Majken S; Chen, Li;

    2015-01-01

    for several malignant and nonmalignant conditions. We screened a library of kinase inhibitors to identify small molecules that enhance bone formation by human skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to inhibit protein kinases A, C, and G) as a potent enhancer of...... differentiation and suggest that pharmacological inhibition of PRKG1 in hMSC implanted at the site of bone defect can enhance bone regeneration. Stem Cells 2015....

  12. Dosimetry of hip irradiation for the prevention of heterotopic bone formation after arthroplasty

    International Nuclear Information System (INIS)

    Purpose: The dosimetry of hip irradiation for the prevention of heterotopic bone formation following arthroplasty is complicated by the use of custom shielding in the treatment portal, and the fact that irradiation is usually required during a 48 hour period following surgery. Both the machine output and depth dose factors of the resulting fields are modified by the presence of the shielding blocks. A simplified dosimetric approach, based on correction factors for both the output and depth dose as a function of field geometry is presented for various megavoltage energy beams. Materials and Methods: Measurements of relative dose factors (RDF) and percentage depth dose (PDD) were carried out for different combinations of field size, block size and separation between adjacent blocks. Both RDF and PDD measurements were made in a water phantom. Ratios of RDF and PDD were obtained by dividing individual measurements or curves by the corresponding values for the open field (i.e., without blocks). The average values of these ratios constitute the correction factors to be applied for a given MU or treatment time calculation. Results: Extensive RDF and PDD measurements reveal that for the field and block dimensions of interest the correction factors for RDF can be parameterized as a function of separation between two adjacent blocks and beam energy alone and the depth correction factors are additionally only a function of depth. The correction factors for depth dose are equally valid for fixed source-skin distance techniques (that use PDD) and fixed source-axis distance techniques (that use TMR). Conclusion: A simple model for the calculation of output in hip irradiation is presented for the situation where the use of computer-based algorithms may not be practical. The model accurately predicts the RDF of the treatment portal to within 2% and the PDD to within 2% for the range of field sizes, block sizes, block gaps and beam energies of interest ignoring other variables

  13. Effect of roasting time of buckwheat groats on the formation of Maillard reaction products and antioxidant capacity.

    Science.gov (United States)

    Małgorzata, Wronkowska; Konrad, Piskuła Mariusz; Zieliński, Henryk

    2016-04-01

    Changes in the formation of Maillard reaction products and antioxidant capacity of buckwheat, induced by roasting at 160 °C for 30, 40 and 50 min, were evaluated in the study. Furozine, was detected after roasting, in all buckwheat samples. Increase of FIC, the presence of significant amounts of CML and enhanced browning were observed, along with increasing times of roasting. The formation of acrylamide in the obtained buckwheat products was also significantly connected with the time of roasting. A significant degradation was observed in natural antioxidants, as affected by heat treatment time. The colour parameter changed significantly with the increasing of roasting time. Overall, 30min of roasting was beneficial from a nutritional point of view for the obtained buckwheat product. PMID:26593501

  14. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

    Science.gov (United States)

    Gowen, M; Stroup, G B; Dodds, R A; James, I E; Votta, B J; Smith, B R; Bhatnagar, P K; Lago, A M; Callahan, J F; DelMar, E G; Miller, M A; Nemeth, E F; Fox, J

    2000-06-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  15. Effect of Bio-Oss ® Collagen and Collagen matrix on bone formation

    OpenAIRE

    Wong, R.W.K; Rabie, A B M

    2010-01-01

    Objective: to compare the amount of new bone produced by Bio-Oss ® Collagen to that produced by collagen matrix in vivo. Method: eighteen bone defects, 5mm by 10mm were created in the parietal bone of 9 New Zealand White rabbits. 6 defects were grafted with Bio-Oss ® Collagen. 6 defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were killed on day 14 and the defects were dissected and prepared for histological assessment. Quant...

  16. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

    Directory of Open Access Journals (Sweden)

    Boos AM

    2014-11-01

    Full Text Available Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Institute of Physics, University of Rostock, Rostock, Germany *These authors contributed equally to this work Abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2, and different carrier materials (fibrin, cell culture medium, autologous serum was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 µg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin. Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly

  17. An intramembranous ossification model for the in silico analysis of bone tissue formation in tooth extraction sites.

    Science.gov (United States)

    Corredor-Gómez, Jennifer Paola; Rueda-Ramírez, Andrés Mauricio; Gamboa-Márquez, Miguel Alejandro; Torres-Rodríguez, Carolina; Cortés-Rodríguez, Carlos Julio

    2016-07-21

    The accurate modeling of biological processes allows us to predict the spatiotemporal behavior of living tissues by computer-aided (in silico) testing, a useful tool for the development of medical strategies, avoiding the expenses and potential ethical implications of in vivo experimentation. A model for bone healing in mouth would be useful for selecting proper surgical techniques in dental procedures. In this paper, the formulation and implementation of a model for Intramembranous Ossification is presented aiming to describe the complex process of bone tissue formation in tooth extraction sites. The model consists in a mathematical description of the mechanisms in which different types of cells interact, synthesize and degrade extracellular matrices under the influence of biochemical factors. Special attention is given to angiogenesis, oxygen-dependent effects and growth factor-induced apoptosis of fibroblasts. Furthermore, considering the depth-dependent vascularization of mandibular bone and its influence on bone healing, a functional description of the cell distribution on the severed periodontal ligament (PDL) is proposed. The developed model was implemented using the finite element method (FEM) and successfully validated by simulating an animal in vivo experiment on dogs reported in the literature. A good fit between model outcome and experimental data was obtained with a mean absolute error of 3.04%. The mathematical framework presented here may represent an important tool for the design of future in vitro and in vivo tests, as well as a precedent for future in silico studies on osseointegration and mechanobiology. PMID:27113783

  18. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    OpenAIRE

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bo...

  19. Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells.

    Science.gov (United States)

    Gao, Guifang; Schilling, Arndt F; Yonezawa, Tomo; Wang, Jiang; Dai, Guohao; Cui, Xiaofeng

    2014-10-01

    Bioprinting based on thermal inkjet printing is a promising but unexplored approach in bone tissue engineering. Appropriate cell types and suitable biomaterial scaffolds are two critical factors to generate successful bioprinted tissue. This study was undertaken in order to evaluate bioactive ceramic nanoparticles in stimulating osteogenesis of printed bone marrow-derived human mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA) scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so the printed substrates were delivered with highly accurate placement in three-dimensional (3D) locations. hMSCs interacted with HA showed the highest cell viability (86.62 ± 6.02%) and increased compressive modulus (358.91 ± 48.05 kPa) after 21 days in culture among all groups. Biochemical analysis showed the most collagen production and highest alkaline phosphatase activity in PEG-HA group, which is consistent with gene expression determined by quantitative PCR. Masson's trichrome staining also showed the most collagen deposition in PEG-HA scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis in bioprinted bone constructs. Combining with our previous experience in vasculature, cartilage, and muscle bioprinting, this technology demonstrates the capacity for both soft and hard tissue engineering with biomimetic structures. PMID:25130390

  20. Analysis of bone formation on porous and calcium phosphate-coated acetabular cups: a randomised clinical [18F]fluoride PET study.

    Science.gov (United States)

    Ullmark, Gösta; Sörensen, Jens; Nilsson, Olle

    2012-01-01

    We present a study using Fluoride-Positron Emission Tomography (F-PET/CT) to analyse new bone formation in periacetabular bone adjacent to press fit cups following THA. In 16 THA (8 patients) with bilateral hip osteoarthritis simultaneous bilateral total hip arthroplasty (THA) was performed, employing electrochemically applied calcium phosphate coated (HA) cups or porous-coated (PC) cups allocated at random to compare the two sides. A reference group of 13 individuals with a normal healthy hip was used to determine 'normal' bone metabolism. [18F]fluoride -PET/CT was used to analyze bone formation adjacent to the cups 1 week, 4 months and 12 months after surgery. Clinical and radiographic evaluation was performed preoperatively, postoperatively and at 2 years. Bone forming activity had a mean of 5.71, 4.69 and 3.47 SUV around the HA- and 5.04, 4.80 and 3.50 SUV around the PC-cups at 1 week, 4 months and 12 months respectively. Normal bone metabolism was 3.68 SUV. After 1 year activity had declined to normal levels for both groups. The clinical results were good in all cases. HA coating resulted in higher uptake indicating higher bone forming activity after 1 week. F-PET/CT is a valuable tool to analyse bone formation and secondary stabilisation of an acetabular cup. PMID:22547382

  1. 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

  2. Selenium supplementation restores the antioxidative capacity and prevents cell damage in bone marrow stromal cells in vitro

    DEFF Research Database (Denmark)

    Ebert, Regina; Ulmer, Matthias; Zeck, Sabine; Meissner-Weigl, Jutta; Schneider, Doris; Stopper, Helga; Schupp, Nicole; Kassem, Moustapha; Jakob, Franz

    2006-01-01

    Bone marrow stromal cells (BMSCs) and other cell populations derived from mesenchymal precursors are developed for cell-based therapeutic strategies and undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS) of cellular and environmental origin are involved in redox...... signaling, cumulative cell damage, senescence, and tumor development. Selenium-dependent (glutathione peroxidases [GPxs] and thioredoxin reductases [TrxRs]) and selenium-independent (superoxide dismutases [SODs] and catalase [CAT]) enzyme systems regulate cellular ROS steady state levels. SODs process...... cultures (5%-10% fetal calf serum, 5-10 nM selenite), the activity of antioxidative selenoenzymes is impaired in hMSC-TERT and BMSCs. Under these conditions, the superoxide anion processing enzyme SOD1 is not sufficiently stimulated by an ROS load. Resulting oxidative stress favors generation of...

  3. 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.

  4. Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone

    Directory of Open Access Journals (Sweden)

    Yoshinobu Uchihara

    2015-01-01

    Full Text Available Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.

  5. Antagonizing the αv β3 integrin inhibits angiogenesis and impairs woven but not lamellar bone formation induced by mechanical loading.

    Science.gov (United States)

    Tomlinson, Ryan E; Schmieder, Anne H; Quirk, James D; Lanza, Gregory M; Silva, Matthew J

    2014-09-01

    Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb. αv β3 integrin-targeted nanoparticles or vehicle was injected intravenously after mechanical loading. β3 integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF-loaded limbs was increased compared with non-loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF- and LBF-loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post-yield behavior. These results demonstrate that αv β3 integrin-mediated angiogenesis is critical for recovering fracture resistance after bone injury but is not required for bone modeling after modest mechanical strain. © 2014 American Society for Bone and Mineral Research. PMID:24644077

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

    DEFF Research Database (Denmark)

    Grubbe, M.-C.; Thomsen, J. S.; 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......BMD, -13%, P<0.001), trabecular bone volume (BV/TV, -26%, P<0.05), and mid-femoral bone strength (-12%, P<0.05). In addition, BTX reduced rectus femoris muscle mass (-69%, P<0.001) and muscle cell cross sectional area (CSA) (-73%, P<0.001) compared with controls. GH counteracted disuse-induced losses of...... periosteal BFR/BS (2-fold increase vs. BTX, P<0.001), whereas no effect on aBMD, trabecular BV/TV, or bone 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...

  7. Antibody formation in mouse bone marrow. II. Evidence for a memory-dependent phenomenon

    International Nuclear Information System (INIS)

    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

  8. Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice

    OpenAIRE

    Yan, Wei; Wang, Ting-Yu; Fan, Qi-ming; Du, Lin; Xu, Jia-ke; Zhai, Zan-jing; Li, Hao-wei; Tang, Ting-ting

    2014-01-01

    Aim: To investigate the effects of plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica, on human breast cancer cell growth and the cancer cell-induced osteolysis in the bone microenvironment of mice. Methods: Human breast cancer cell subline MDA-MB-231SA with the ability to spread and grow in the bone was tested. The cell proliferation was determined using the CCK-8 assay. Apoptosis was detected with Annexin V/PI double-labeled flow cytometry. Red fluorescent prote...

  9. Conditional disruption of miR17-92 cluster in collagen type I-producing osteoblasts results in reduced periosteal bone formation and bone anabolic response to exercise.

    Science.gov (United States)

    Mohan, Subburaman; Wergedal, Jon E; Das, Subhashri; Kesavan, Chandrasekhar

    2015-02-01

    In this study, we evaluated the role of the microRNA (miR)17-92 cluster in osteoblast lineage cells using a Cre-loxP approach in which Cre expression is driven by the entire regulatory region of the type I collagen α2 gene. Conditional knockout (cKO) mice showed a 13-34% reduction in total body bone mineral content and area with little or no change in bone mineral density (BMD) by DXA at 2, 4, and 8 wk in both sexes. Micro-CT analyses of the femur revealed an 8% reduction in length and 25-27% reduction in total volume at the diaphyseal and metaphyseal sites. Neither cortical nor trabecular volumetric BMD was different in the cKO mice. Bone strength (maximum load) was reduced by 10% with no change in bone toughness. Quantitative histomorphometric analyses revealed a 28% reduction in the periosteal bone formation rate and in the mineral apposition rate but with no change in the resorbing surface. Expression levels of periostin, Elk3, Runx2 genes that are targeted by miRs from the cluster were decreased by 25-30% in the bones of cKO mice. To determine the contribution of the miR17-92 cluster to the mechanical strain effect on periosteal bone formation, we subjected cKO and control mice to 2 wk of mechanical loading by four-point bending. We found that the periosteal bone response to mechanical strain was significantly reduced in the cKO mice. We conclude that the miR17-92 cluster expressed in type I collagen-producing cells is a key regulator of periosteal bone formation in mice. PMID:25492928

  10. Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation.

    Science.gov (United States)

    Rappl, Gunter; Pabst, Stefan; Riemann, Dagmar; Schmidt, Annette; Wickenhauser, Claudia; Schütte, Wolfgang; Hombach, Andreas A; Seliger, Barbara; Grohé, Christian; Abken, Hinrich

    2011-07-01

    Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4(+)CD25(high)FoxP3(+) regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M. PMID:21482483

  11. Study of formation constant of molybdophosphate and it's application in the product of xenotime sand, tooth and bone

    International Nuclear Information System (INIS)

    The formation constant of molybdophosphate complex and it's application in the product of xenotime sand, tooth and bone have been studied by spectrophotometric method. The molybdophosphate complex were formed from reaction between phosphate and molybdate on several of pH in the strong acid condition (pH = 0.45 - 0.71) and several of phosphate mole fraction (0.01 - 0.08). The several of complex formation reactions were determined by matrix disintegration technique. Molybdophosphate complex were founded three forms i.e. (P2Mo18O62)6- or 9 MPA, (PMo11O39)7- or 11 MPA and (PMo12O40)3- or 12 MPA. The formation constant of (PMo12O40)3- complex was found β = 1046.95 ± 103.7, while for (P2Mo18O62)6- and (PMo11O39)7- were not detected. The application in samples were found the concentration of P in product of xenotime sand : 5.37±0.08 μg/ml, in canine-tooth: 10.40 - 19.49 % in cutting-tooth : 11.08 - 18.05 % and in bone 10.94 - 14.29 %. (author)

  12. Bone marrow cells participate in tumor vessel formation that supports the growth of Ewing’s sarcoma in the lung

    OpenAIRE

    Zhou, Zhichao; Stewart, Keri Schadler; Yu, Ling; Kleinerman, Eugenie S.

    2010-01-01

    An MHC-mismatch bone marrow (BM) transplant Ewing’s sarcoma mouse model was used to investigate whether BM cells participate in the vessel formation that support Ewing’s sarcoma lung metastasis. BM cells from H-2Kb/d donor mice were transplanted into sublethally irradiated H-2Kd recipient mice. Donor BM cells were identified using the H-2Kb marker. Engraftment was confirmed by identifying the H-2Kb IL-1β-type specific polymorphism. After engraftment highly lung metastatic TC71-PM4 cells were ...

  13. 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...

  14. Effects of prostaglandin F2 alpha on bone formation and resorption in cultured neonatal mouse calvariae: Role of prostaglandin E2 production

    International Nuclear Information System (INIS)

    Although most studies show that prostaglandin E2 (PGE2) is the most potent and effective of the prostanoids in bone, recent data in cell culture suggest that PGF2 alpha may have unique effects, particularly on cell replication. The present study was undertaken to compare the effects of PGF2 alpha and PGE2 in cultured neonatal mouse parietal bones by simultaneous measurement of bone resorption as release of previously incorporated 45Ca, bone formation as incorporation of [3H]proline into collagenase-digestible (CDP) and noncollagen protein, and DNA synthesis as incorporation of [3H]thymidine. PGF2 alpha was less effective than PGE2 as a stimulator of bone resorption, and its effects were partially inhibited by indomethacin and markedly inhibited by glucocorticoids. In contrast, the resorptive response to PGE2 was unaffected by indomethacin and only partially inhibited by cortisol. PGF2 alpha had little effect on bone formation, in contrast to the biphasic effect of PGE2, which inhibited labeling of CDP in the absence of cortisol and stimulated CDP labeling in the presence of cortisol. PGF2 alpha increased thymidine incorporation into DNA, but the effect was smaller than that of PGE2 and was inhibited by indomethacin. These observations suggested that PGF2 alpha might act in part by stimulating PGE2 production. By RIA, PGE2 concentrations were increased in the medium of bones treated with PGF2 alpha, and this increase was blocked by indomethacin. By HPLC, bones prelabeled with [3H]arachidonic acid showed an increase in labeled PGE2 release, and RIA showed an increase in PGE2 after PGF2 alpha treatment. These results indicate that PGF2 alpha is a relatively weak agonist in bone compared to PGE2 and that some of the effects of PGF2 alpha on bone resorption, formation, and cell replication may be mediated by an increase in endogenous PGE2 production

  15. Human Histologic and Radiographic Evidence of Bone Formation in a Previously Infected Maxillary Sinus Graft Following Debridement Without Regrafting: A Case Report.

    Science.gov (United States)

    Khouly, Ismael; Phelan, Joan A; Muñoz, Carlos; Froum, Stuart J

    2016-01-01

    The aim of this case report was to evaluate the histologic and radiographic new bone formation following maxillary sinus reentry surgery without a bone graft. A 61-year-old woman was referred with a failure of a sinus augmentation procedure. A reentry procedure was performed to retreat the sinus complication. The procedure involved removal of the bone graft plus debridement of the sinus. No additional bone graft material was used. A cone beam computed tomography scan was taken 6 months following the reentry procedure. During implant placement surgery, a core biopsy specimen was retrieved, stored, and prepared to obtain thin ground undecalcified sections. The histologic and radiographic analysis showed formation of new bone at the time of implant placement. At 18 months following implant placement, successful evidence of integration was determined by implant stability and radiographs. Space maintained by the previously elevated sinus membrane at the time of sinus reentry was sufficient to induce formation of bone without regrafting. However, more cases involving survival of implants placed in augmented sinuses without the use of bone grafts at the time of reentry are needed to confirm the results of this case report study. PMID:27560677

  16. Albumin synthesis and bone collagen formation in human immunodeficiency virus-positive subjects: differential effects of growth hormone administration.

    Science.gov (United States)

    McNurlan, M A; Garlick, P J; Frost, R A; Decristofaro, K A; Lang, C H; Steigbigel, R T; Fuhrer, J; Gelato, M

    1998-09-01

    Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P 10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P < 0.05), HIV+ subjects (39 +/- 16%, P < 0.05), and patients with AIDS (25 +/- 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH. PMID:9745402

  17. Enhancement of Osteoclastic Bone Resorption and Suppression of Osteoblastic Bone Formation in Response to Reduced Mechanical Stress Do Not Occur in the Absence of Osteopontin

    OpenAIRE

    Ishijima, Muneaki; Rittling, Susan R; Yamashita, Teruhito; Tsuji, Kunikazu; Kurosawa, Hisashi; Nifuji, Akira; Denhardt, David T.; Noda, Masaki

    2001-01-01

    Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investi...

  18. Bone grafts in dentistry

    OpenAIRE

    Prasanna Kumar; Belliappa Vinitha; Ghousia Fathima

    2013-01-01

    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.

  19. 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.

  20. 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.

  1. 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.

  2. Inhibition of cathepsin K increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeys.

    Science.gov (United States)

    Pennypacker, Brenda L; Chen, Charles M; Zheng, Helen; Shih, Mei-Shu; Belfast, Mary; Samadfam, Rana; Duong, Le T

    2014-08-01

    Treatment with the cathepsin K (CatK) inhibitor odanacatib (ODN) protects against bone loss and maintains normal biomechanical properties in the spine and hip of ovariectomized (OVX) preclinical models. Here, we characterized the effects of ODN on the dynamics of cortical modeling and remodeling, and dimension and strength of the central femur in adult OVX-rhesus monkeys. Animals were treated with vehicle or ODN (6 or 30 mg/kg, once per day [q.d., p.o.]) in prevention mode for 21 months. Calcein and tetracycline double-labeling were given at 12 and 21 months, and the femoral cross-sections were subjected to dynamic histomorphometric and cement line analyses. ODN treatment significantly increased periosteal and endocortical bone formation (BFR/BS), accompanied with an increase in endocortical mineralizing surface (102%, p < 0.01) with the 6 mg/kg dose. ODN at both doses reduced remodeling hemiosteon numbers by 51% and 66% (p < 0.05), respectively, and ODN 30 mg/kg numerically reduced activation frequency without affecting wall thickness. On the same endocortical surface, ODN increased all modeling-based parameters, while reducing intracortical remodeling, consistent with the observed no treatment effects on cortical porosity. ODN 30 mg/kg markedly increased cortical thickness (CtTh, p < 0.001) and reduced marrow area (p < 0.01). Lastly, ODN treatment increased femoral structural strength (p < 0.001). Peak load was positively correlated with the increases in bone mineral content (BMC) (r(2)  = 0.9057, p < 0.0001) and CtTh (r2  = 0.6866, p < 0.0001). Taken together, by reducing cortical remodeling-based and stimulating modeling-based bone formation, ODN significantly improved cortical dimension and strength in OVX monkeys. This novel mechanism of CatK inhibition in stimulating cortical formation suggests that ODN represents a novel therapeutic approach for the treatment of osteoporosis. PMID:24591096

  3. IGF-I Signaling in Osterix-Expressing Cells Regulates Secondary Ossification Center Formation, Growth Plate Maturation, and Metaphyseal Formation During Postnatal Bone Development.

    Science.gov (United States)

    Wang, Yongmei; Menendez, Alicia; Fong, Chak; ElAlieh, Hashem Z; Kubota, Takuo; Long, Roger; Bikle, Daniel D

    2015-12-01

    To investigate the role of IGF-I signaling in osterix (OSX)-expressing cells in the skeleton, we generated IGF-I receptor (IGF-IR) knockout mice ((OSX)IGF-IRKO) (floxed-IGF-IR mice × OSX promoter-driven GFP-labeled cre-recombinase [(OSX)GFPcre]), and monitored postnatal bone development. At day 2 after birth (P2), (OSX)GFP-cre was highly expressed in the osteoblasts in the bone surface of the metaphysis and in the prehypertrophic chondrocytes (PHCs) and inner layer of perichondral cells (IPCs). From P7, (OSX)GFP-cre was highly expressed in PHCs, IPCs, cartilage canals (CCs), and osteoblasts (OBs) in the epiphyseal secondary ossification center (SOC), but was only slightly expressed in the OBs in the metaphysis. Compared with the control mice, the IPC proliferation was decreased in the (OSX)IGF-IRKOs. In these mice, fewer IPCs invaded into the cartilage, resulting in delayed formation of the CC and SOC. Immunohistochemistry indicated a reduction of vessel number and lower expression of VEGF and ephrin B2 in the IPCs and SOC of (OSX)IGF-IRKOs. Quantitative real-time PCR revealed that the mRNA levels of the matrix degradation markers, MMP-9, 13 and 14, were decreased in the (OSX)IGF-IRKOs compared with the controls. The (OSX)IGF-IRKO also showed irregular morphology of the growth plate and less trabecular bone in the tibia and femur from P7 to 7 weeks, accompanied by decreased chondrocyte proliferation, altered chondrocyte differentiation, and decreased osteoblast differentiation. Our data indicate that during postnatal bone development, IGF-I signaling in OSX-expressing IPCs promotes IPC proliferation and cartilage matrix degradation and increases ephrin B2 production to stimulate vascular endothelial growth factor (VEGF) expression and vascularization. These processes are required for normal CC formation in the establishment of the SOC. Moreover, IGF-I signaling in the OSX-expressing PHC is required for growth plate maturation and osteoblast differentiation in

  4. 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.

  5. Possible ways whereby IL-2 stimulates colony formation by cells of in vitro irradiated bone marrow

    International Nuclear Information System (INIS)

    The authors have made an attempt to find out the reasons of IL-2-stimulation of spleen colony growth by in vitro (1 Gy) irradiated bone marrow cells. It was shown that the effect of IL on haemopoiesis manifests itself with merely small radiation doses implying that the influence of the preparation makes the process of haemopoietic organ repopulation start at a higher level of cell survival, which is presumably related to a more active repair of radiation-induced CFUs damages: this leads, with other things being equal (e.g. proliferation rate and f factor), to a higher yield of colonies than it is observed with the recipients protected with the exposed bone marrow only

  6. Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury.

    Directory of Open Access Journals (Sweden)

    Alayna E Loiselle

    Full Text Available The pathogenesis of adhesions following primary tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps. We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine flexor digitorum (FDL tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9(-/- mice using the FDL tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9(-/- mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP(+ migrated specifically to the tendon repair site. Transplanting myeloablated Mmp9(-/- mice with WT marrow cells resulted in greater adhesions than observed in Mmp9(-/- mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing.

  7. Pyk2 Regulates Megakaryocyte-Induced Increases in Osteoblast Number and Bone Formation

    OpenAIRE

    Cheng, Ying-Hua; Hooker, R. Adam; NGUYEN, Khanh; Gerard-O’Riley, Rita; Waning, David L.; Chitteti, Brahmananda R; Meijome, Tomas E.; Chua, Hui Lin; Plett, Artur P.; Orschell, Christie M.; Srour, Edward F.; Mayo, Lindsey D.; Pavalko, Fredrick M; Bruzzaniti, Angela; Kacena, Melissa A.

    2013-01-01

    Pre-clinical and clinical evidence from megakaryocyte (MK) related diseases suggest that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We therefore examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 l...

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

    OpenAIRE

    Yoshitomo Honda; Tomonari Tanaka; Tomoko Tokuda; Takahiro Kashiwagi; Koji Kaida; Ayato Hieda; Yasuyuki Umezaki; Yoshiya Hashimoto; Koichi Imai; Naoyuki Matsumoto; Shunsuke Baba; Kimishige Shimizutani

    2015-01-01

    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 facilita...

  9. Palm Tocotrienol Supplementation Enhanced Bone Formation in Oestrogen-Deficient Rats

    OpenAIRE

    Ima Nirwana Soelaiman; Wang Ming; Roshayati Abu Bakar; Nursyahrina Atiqah Hashnan; Hanif Mohd Ali; Norazlina Mohamed; Norliza Muhammad; Ahmad Nazrun Shuid

    2012-01-01

    Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementa...

  10. 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.

  11. 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

    Institute of Scientific and Technical Information of China (English)

    Feng Xue; Er-jun Wu; Pei-xun Zhang; Li-ya A; Yu-hui Kou; Xiao-feng Yin; Na Han

    2015-01-01

    We examined the restorative effect of modiifed 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 transplantationin vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial ifbrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve ifbers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our ifndings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvi-ronment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  12. 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

    OpenAIRE

    Feng Xue; Er-jun Wu; Pei-xun Zhang; Li-ya A; Yu-hui Kou; Xiao-feng Yin; Na Han

    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 fo...

  13. Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

    Science.gov (United States)

    Conover, Cheryl A.; Johnstone, Edward W.; Turner, Russell T.; Evans, Glenda L.; John Ballard, F. John; Doran, Patrick M.; Khosla, Sundeep

    2002-01-01

    Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (PIGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (PIGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

  14. Overexpression of H1 Calponin in Osteoblast Lineage Cells Leads to a Decrease in Bone Mass by Disrupting Osteoblast Function and Promoting Osteoclast Formation

    OpenAIRE

    Su, Nan; Chen, Maomao; Chen, Siyu; Li, Can; Xie, Yangli; Zhu, Ying; Zhang, Yaozong; Zhao, Ling; He, Qifen; Du, Xiaolan; Chen, Di; Chen, Lin

    2013-01-01

    H1 calponin (CNN1) is known as a smooth muscle-specific, actin-binding protein which regulates smooth muscle contractive activity. Although previous studies have shown that CNN1 has effect on bone, the mechanism is not well defined. To investigate the role of CNN1 in maintaining bone homeostasis, we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast-specific 3.6-kb Col1a1 promoter. Col1a1-Cnn1 transgenic mice showed delayed bone formation at embryonic stage and ...

  15. Transplanting defrozen mouse bone marrow cells

    International Nuclear Information System (INIS)

    The regeneration was studied of blood formation in the spleen and the bone marrow of lethally irradiated mice 30 and 60 days after the transplantation of defrozen bone marrow. Also studied were the counts of leukocytes, thrombocytes and reticulocytes in the peripheral blood. Hematopoiesis changes were described and it was shown that after the transplantation of defrozen bone marrow, regeneration and progressive normalization of hematopoiesis took place in the lethally irradiated recipients. It was found that the freezing procedure used was tender and preserved the proliferation capacity of the stem hemopoietic cells. (author)

  16. 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)

    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 α6 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

  17. Effect of alpha-tocopherol on bone formation during distraction osteogenesis: a rabbit model

    OpenAIRE

    Kurklu, Mustafa; Yildiz, Cemil; Kose, Ozkan; Yurttas, Yuksel; Karacalioglu, Ozgur; Serdar, Muhittin; Deveci, Salih

    2011-01-01

    Purpose The purpose of this study was to evaluate the effects of alpha-tocopherol on distraction osteogenesis. Materials and methods Right tibias of 30 New Zealand white rabbits were distracted at a rate of 0.5 mm/day for 20 days with a circular external fixator. Experimental group rabbits (n = 15) were administered i.m. 20 mg/kg/day alpha-tocopherol for 30 days. Radiographic examinations were performed at the 20th, 30th and 40th days. Bone scintigraphy was performed at the 5th and 20th days....

  18. 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

  19. BONE IN OSTEOPETROSIS

    Directory of Open Access Journals (Sweden)

    Ramkumar

    2014-04-01

    Full Text Available Osteopetrosis, a generalized developmental bone disease due to genetic disturbances, characterized by failure of bone re sorption and continuous bone formation making the bone hard, dense and brittle. Bones of intramembranous ossification and enchondrial ossification are affected genetically and symmetrically. During the process of disease the excess bone formation obliterates the cranial foramina and presses the optic, auditory and facial nerves resulting in defective vision, impaired hearing and facial paralysis. The bone formation in osteopetrosis affects bone marrow function leading to severe anemia and deficient of blood cells. The bone devoid of blood supply due to compression of blood vessels by excess formation of bone are prone to osteomyelitic changes with suppuration and pathological fracture if exposed to infection. Though the condition is chronic progressive, it produces changes leading to fatal condition, it should be studied thoroughly by everyone and hence this article presents a classical case of osteopetrosis with detailed description and discussion for the benefit of readers

  20. Antiangiogenic treatment delays chondrocyte maturation and bone formation during limb skeletogenesis.

    Science.gov (United States)

    Yin, Melinda; Gentili, Chiara; Koyama, Eiki; Zasloff, Michael; Pacifici, Maurizio

    2002-01-01

    Hypertrophic chondrocytes have important roles in promoting invasion of cartilage by blood vessels and its replacement with bone. However, it is unclear whether blood vessels exert reciprocal positive influences on chondrocyte maturation and function. Therefore, we implanted beads containing the antiangiogenic molecule squalamine around humeral anlagen in chick embryo wing buds and monitored the effects over time. Fluorescence microscopy showed that the drug diffused from the beads and accumulated in humeral perichondrial tissues, indicating that these tissues were the predominant targets of drug action. Diaphyseal chondrocyte maturation was indeed delayed in squalamine-treated humeri, as indicated by reduced cell hypertrophy and expression of type X collagen, transferrin, and Indian hedgehog (Ihh). Although reduced in amount, Ihh maintained a striking distribution in treated and control humeri, being associated with diaphyseal chondrocytes as well as inner perichondrial layer. These decreases were accompanied by lack of cartilage invasion and tartrate-resistant acid phosphatase-positive (TRAP+) cells and a significant longitudinal growth retardation. Recovery occurred at later developmental times, when in fact expression in treated humeri of markers such as matrix metalloproteinase 9 (MMP-9) and connective tissue growth factor (CTGF) appeared to exceed that in controls. Treating primary cultures of hypertrophic chondrocytes and osteoblasts with squalamine revealed no obvious changes in cell phenotype. These data provide evidence that perichondrial tissues and blood vessels in particular influence chondrocyte maturation in a positive manner and may cooperate with hypertrophic chondrocytes in dictating the normal pace and location of the transition from cartilage to bone. PMID:11771670

  1. Evaluation of Different Combinations of Biphasic Calcium Phosphate and Growth Factors for Bone Formation in Calvarial Defects in a Rabbit Model.

    Science.gov (United States)

    Chung, Sung-Min; Jung, In Kwon; Yoon, Byung-Ho; Choi, Bok Ryul; Kim, David M; Jang, Jung Sun

    2016-01-01

    The aim of the present preclinical study was to investigate the capability of a new formulation of biphasic calcium phosphate (BCP) in achieving new bone formation either by itself or in combination with different concentrations of growth factors. Twenty-four 3-month-old male New Zealand white rabbits (weight range, 2.5 to 3.0 kg) that had been bred exclusively for biomedical research purposes and obtained from a licensed vendor were used. Four calvarial defects were created in each animal, for a total of 96 defects. Each defect received alloplastic BCP (Osteon III, Genoss) that was composed of 60% hydroxyapatite and 40% β-tricalcium phosphate) (porosity, ~80%; macropore size, 200 to 400 μm; crystallinity, 95%) combined with different concentrations of recombinant human platelet-derived growth factor BB (rhPDGF-BB), human recombinant basic fibroblast growth factor-2 (rhFGF-2), or recombinant human bone morphogenetic protein-2 (rhBMP-2). A custom-made polycarbonate tube was fixed to each defect site by applying slight pressure, and a mixture of bone graft and growth factor was implanted into the tubes. Data were collected 2, 4, and 8 weeks after creation of the defects to assess early and late healing. Various amounts of newly formed bone and remnant BCP particles formed inside of the tube throughout the study period. The BCP + 0.5 mg/mL rhBMP-2 group exhibited the most bone formation. At 8 weeks, more new bone formation was noted in the Osteon III + rhBMP-2 combined group than in other groups. The present study results indicate that BCP can be combined with different concentrations of rhBMP-2, rhFGF-2, and rhPDGF-BB to produce new bone formation within a polycarbonate tube in calvarial defects in a rabbit model. PMID:27031634

  2. Ectopic bone formation and chondrodysplasia in transgenic mice carrying the rat C3(1)/T{sub AG} fusion gene

    Energy Technology Data Exchange (ETDEWEB)

    Green, J.E.; Maroulakou, I.G.; Anver, M. [National Cancer Institute, Frederick, MD (United States)] [and others

    1994-09-01

    Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy. Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.

  3. 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.

  4. High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

    Institute of Scientific and Technical Information of China (English)

    Li YOU; Zheng-yan SHENG; Chuan-ling TANG; Lin CHEN; Ling PAN; Jin-yu CHEN

    2011-01-01

    To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats.Methods:Female Sprague-Dawley rats were randomly separated into 3 groups:(1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food,3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet.Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry.Serum levels of oestradiol (E2),osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA.Gene expression profile was determined with microarray.Mouse osteoblast cells (MC3T3-E1) were used for in vitro study.Proliferation,differentiation and oxidative stress of the osteoblasts were investigated using MTT,qRT-PCR and biochemical methods.Results:In high cholesterol fed rats,the femur BMD and serum BGP level were significantly reduced,while the CTX level was significantly increased.DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats.Of these genes,1626 were also down-regulated and 1466 were up-regulated in OVX rats.In total,370 genes were up-regulated in both groups,and 976 genes were down-regulated.Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways.The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions.Treatment of MC3T3-E1 cells with cholesterol (12.5-50μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner.The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1,and increased the oxidative injury in MC3T3-E1 cells.Conclusion:The results suggest a close

  5. Effects of Daily or Cyclic Teriparatide on Bone Formation in the Iliac Crest in Women on No Prior Therapy and in Women on Alendronate.

    Science.gov (United States)

    Dempster, David W; Cosman, Felicia; Zhou, Hua; Nieves, Jeri W; Bostrom, Mathias; Lindsay, Robert

    2016-08-01

    There is little information on the effects of combination therapy for osteoporosis at the tissue level. Using quadruple tetracycline-labeled bone biopsies, we have compared the bone formation response to teriparatide (TPTD) in treatment-naïve subjects (Rx-Naïve) and in subjects on prior and ongoing alendronate (ALN) treatment (ALN-Rx). Three bone envelopes were analyzed: cancellous, endocortical, and intracortical. TPTD was given as a standard, continuous daily injection or as a cyclic regimen (3 months on daily TPTD, 3 months off, 3 months on daily TPTD). Subjects were biopsied at 7 weeks and at 7 months to allow comparison of the bone formation response to the first and second cycles of TPTD. Baseline values for dynamic bone formation indices were lower in ALN-Rx than Rx-Naïve subjects. Both Rx-Naïve and ALN-RX subjects responded to TPTD with significant increases in bone formation indices at both time points. With cyclic TPTD treatment, the first and second cycles of TPTD stimulated bone formation rate in the cancellous and endocortical envelopes to a similar extent in ALN-Rx and Rx-Naïve subjects. However, in Rx-Naïve patients, bone formation rate (BFR/BS) was higher in patients receiving daily treatment compared with those receiving cyclic TPTD treatment in all three envelopes in the 7-month biopsies. This suggests that the cyclic approach does not provide a skeletal benefit in treatment-naive patients. In the 7-month biopsies, cortical porosity was higher in the Rx-Naïve group receiving daily TPTD than in all other groups. These data provide supporting evidence at the tissue level for previous biochemical and densitometric data suggesting that addition of either cyclic or daily TPTD to ongoing ALN treatment may be an effective approach for patients with severe osteoporosis already treated with ALN who remain at high risk of fracture. © 2016 American Society for Bone and Mineral Research. PMID:26916877

  6. Radiation-induced micronucleus formation in mice bone marrow after exposure to different doses of 60Co gamma radiation

    International Nuclear Information System (INIS)

    The frequency of micronuclei formation in the polychromatic erythrocytes and normochromatic erythrocytes was studied at 12 and 24th post-irradiation in mice bone marrow whole-body exposed to 0, 0.5, 1.0, 2.0, 3.0 and 4.0 Gy of 60Co gamma radiation. It was observed that the frequency of MPCE (micronucleated polychromatic erythrocytes) and MNCE (micronucleated normochromatic erythrocytes) increased with increase in exposure dose in both intervals studied. The data analyzed using the linear quadratic (Y+C+αD+βD2) equation. It was found that the data for MPCE and MNCE fitted best for linear quadratic model. (The PCE/NCE ratio declined with increase in exposure dose in both intervals and this decline was dose related. (author). 28 refs., 1 tab

  7. De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-10-01

    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. PMID:26254180

  8. Antibody formation in mouse bone marrow. IV. The influence of splenectomy on the bone marrow plaque-forming cell response to sheep red blood cells

    International Nuclear Information System (INIS)

    Mouse bone marrow is barely capable of plaque-forming cell (PFC) activity during the primary response to sheep red blood cells (SRBC). However, during the secondary response, it becomes the major center of activity containing IgM-, IgG- and IgA-PFC. In the present paper the influence of splenectomy was studied on primary and secondary PFC activity in the bone marrow. Differences in primary and secondary bone marrow PFC responses are probably related to the presence of B and T memory cells in situ. Therefore the effect of splenectomy on the appearance of B and T memory cells in the bone marrow was also investigated. iv.plenectomy before intravenous (iv) immunization with 4 x 108 SRBC prevented any primary PFC activity in the bone marrow. The influence of splenectomy before priming on secondary PFC activity in the bone marrow depended on the priming dose of SRBC. Splenectomy before priming with 107 SRBC iv completely prevented IgM-, IgG-, and IgA-PFC activity in the bone marrow upon subsequent boosting with 4 x 108 SRBC iv. By means of cell transfer experiments it was shown that after splenectomy no B or T memory cells appeared in the bone marrow after priming with 107 SRBC iv. Cell transfer experiments showed that splenectomy before priming with 107 SRBC iv not only interfered with the appearance of B and T memory cells in the bone marrow, but also with the appearance of B memory cells in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus, and blood. Immunization of spenectomized mice with 4 x 108 SRBC iv induced the appearance of B memory cells in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus, and blood

  9. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis.

    Science.gov (United States)

    Goldring, Steven R

    2012-08-01

    The articular cartilage and the subchondral bone form a biocomposite that is uniquely adapted to the transfer of loads across the diarthrodial joint. During the evolution of the osteoarthritic process biomechanical and biological processes result in alterations in the composition, structure and functional properties of these tissues. Given the intimate contact between the cartilage and bone, alterations of either tissue will modulate the properties and function of the other joint component. The changes in periarticular bone tend to occur very early in the development of OA. Although chondrocytes also have the capacity to modulate their functional state in response to loading, the capacity of these cells to repair and modify their surrounding extracellular matrix is relatively limited in comparison to the adjacent subchondral bone. This differential adaptive capacity likely underlies the more rapid appearance of detectable skeletal changes in OA in comparison to the articular cartilage. The OA changes in periarticular bone include increases in subchondral cortical bone thickness, gradual decreases in subchondral trabeular bone mass, formation of marginal joint osteophytes, development of bone cysts and advancement of the zone of calcified cartilage between the articular cartilage and subchondral bone. The expansion of the zone of calcified cartilage contributes to overall thinning of the articular cartilage. The mechanisms involved in this process include the release of soluble mediators from chondrocytes in the deep zones of the articular cartilage and/or the influences of microcracks that have initiated focal remodeling in the calcified cartilage and subchondral bone in an attempt to repair the microdamage. There is the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the

  10. 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. PMID:27007721

  11. Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model

    Science.gov (United States)

    Kim, Sungtae; Kim, Se Won; Lee, Jong Ho

    2016-01-01

    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. PMID:27047963

  12. 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

    2016-01-01

    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. PMID:26927080

  13. On regularities in the formation of structure-functional types of chromosome combinations in the bone marrow of intact experimental rats

    International Nuclear Information System (INIS)

    The bone marrow formation of three structure-functional types of chromosome-combinations was studied on intact rats at diverse age periods and experimental models of splenectomy, aseptic inflammation, hypoxic state, hemorrhage, and irradiation. As a result, a dependence was revealed of their formation intensity upon the ontogenesis stage as well as upon the nature and power of the experimental factor affecting the organism

  14. Surface modification of PCL-TCP scaffolds improve interfacial mechanical interlock and enhance early bone formation : An in vitro and in vivo characterization

    NARCIS (Netherlands)

    Yeo, A.; Wong, W. J.; Khoo, H. H.; Teoh, S. H.

    2010-01-01

    Pretreatment of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds under alkaline conditions can be utilized to alter surface characteristics for enhanced early bone formation. PCL-TCP scaffolds were treated with sodium hydroxide (NaOH) at various time intervals (group A: untreated, group

  15. 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

  16. ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

    OpenAIRE

    C. Rentsch; Rentsch, B.; Heinemann, S.; Bernhardt, R; Bischoff, B; Förster, Y; Scharnweber, D.; Rammelt, S

    2014-01-01

    Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influe...

  17. Tissue growth controlled by geometric boundary conditions: a simple model recapitulating aspects of callus formation and bone healing.

    Science.gov (United States)

    Fischer, F Dieter; Zickler, Gerald A; Dunlop, John W C; Fratzl, Peter

    2015-06-01

    The shape of tissues arises from a subtle interplay between biochemical driving forces, leading to cell growth, division and extracellular matrix formation, and the physical constraints of the surrounding environment, giving rise to mechanical signals for the cells. Despite the inherent complexity of such systems, much can still be learnt by treating tissues that constantly remodel as simple fluids. In this approach, remodelling relaxes all internal stresses except for the pressure which is counterbalanced by the surface stress. Our model is used to investigate how wettable substrates influence the stability of tissue nodules. It turns out for a growing tissue nodule in free space, the model predicts only two states: either the tissue shrinks and disappears, or it keeps growing indefinitely. However, as soon as the tissue wets a substrate, stable equilibrium configurations become possible. Furthermore, by investigating more complex substrate geometries, such as tissue growing at the end of a hollow cylinder, we see features reminiscent of healing processes in long bones, such as the existence of a critical gap size above which healing does not occur. Despite its simplicity, the model may be useful in describing various aspects related to tissue growth, including biofilm formation and cancer metastases. PMID:26018964

  18. Improved Bone Formation in Osteoporotic Rabbits with the Bone Morphogenetic Protein-2 (rhBMP-2) Coated Titanium Screws Which Were Coated By Using Plasma Polymerization Technique

    OpenAIRE

    Salih Gulsen; Dilek Cokeliler; Hilal Goktas; Aysu Kucukturhan; Bilgehan Ozcil; Hakan Caner

    2014-01-01

    Delaying of bone fusion in osteoporotic patients underwent spinal stabilization surgery leads to screw loosening, and this causes pseudoarticulation, mobility and fibrosis at vertebral segments. To prevent these complications, the screws coated with recombinant bone morphogenetic protein-2 (rhBMP-2) could be used. To verify this hypothesis, we coated 5 Titanium screws with rhBMP-2 using plasma polymerization method, and also used 10 uncoated screws for making comparison between coated and unc...

  19. von Kossa staining alone is not sufficient to confirm that mineralization in vitro represents bone formation.

    Science.gov (United States)

    Bonewald, L F; Harris, S E; Rosser, J; Dallas, M R; Dallas, S L; Camacho, N P; Boyan, B; Boskey, A

    2003-05-01

    Numerous techniques are currently used to characterize biological mineralization in intact tissues and cell cultures; the von Kossa staining method, electron microscopic analysis (EM), X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR) are among the most common. In this study, we utilized three of these methods to compare the mineralization of cultured fetal rat calvarial cells (FRC) and the osteoblast cell lines 2T3 and MC3T3-E1 with the in vivo mineral of rat calvarial bone. The cells were cultured with or without ascorbic acid (100 microg/ml) and beta-glycerophosphate (2.5, 5, or 10 mM betaGP), and harvested between 16 and 21 days (FRC cells and 2T3 cells) or at 30 days of culture (MC3T3-E1 cells). In the FRC cultures, maximal von Kossa staining was observed with 2.5 and 5 mM betaGP in the presence of 100 microg/ml ascorbate. FRC cells also showed some von Kossa staining when cultured with bGP alone. In contrast, maximal von Kossa staining for MC3T3-E1 cells was observed with 10 mM betaGP. Only the cultures of MC3T3-E1 cells that received both ascorbate and betaGP produced von Kossa positive structures. The 2T3 cultures produced von Kossa positive staining only upon treatment with ascorbic acid and betaGP, which was greatly accelerated by bone morphogenic protein-2 (BMP-2). FTIR was performed on the mineral and matrix generated in FRC, MC3T3, and 2T3 cultures, and the results were compared with spectra derived from 16-day-old rat calvaria. The mineral-to-matrix ratios calculated from FTIR spectra for rat calvaria ranged from 2.97 to 7.44. FRC cells made a bonelike, poorly crystalline apatite, and, with increasing betaGP, there was a statistically significant (Pmineral-to-matrix ratio (0.56 +/- 0.16, 1.00 +/- 0.32, and 2.46 +/- 0.76, for 2.5, 5, and 10 mM betaGP, respectively). The mean carbonate-to-phosphate ratios of the FRC cultures were 0.015, 0.012, and 0.008, in order of increasing bGP concentration, compared with rat calvaria values of 0

  20. Bone Marrow Stress Decreases Osteogenic Progenitors.

    Science.gov (United States)

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  1. Bone formation in vivo induced by Cbfa1-carrying adenoviral vectors released from a biodegradable porous {beta}-tricalcium phosphate ({beta}-TCP) material

    Energy Technology Data Exchange (ETDEWEB)

    Uemura, Toshimasa; Kojima, Hiroko, E-mail: t.uemura@aist.go.jp [Nanosystem Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba Central-4, Tsukuba, Ibaraki 305-8562 (Japan)

    2011-06-15

    Overexpression of Cbfa1 (a transcription factor indispensable for osteoblastic differentiation) is expected to induce the formation of bone directly and indirectly in vivo by accelerating osteoblastic differentiation. Adenoviral vectors carrying the cDNA of Cbfa1/til-1(Adv-Cbf1) were allowed to be adsorbed onto porous blocks of {beta}-tricalcium phosphate ({beta}-TCP), a biodegradable ceramic, which were then implanted subcutaneously and orthotopically into bone defects. The adenoviral vectors were released sustainingly by biodegradation, providing long-term expression of the genes. Results of the subcutaneous implantation of Adv-Cbfa1-adsorbed {beta}-TCP/osteoprogenitor cells suggest that a larger amount of bone formed in the pores of the implant than in the control material. Regarding orthotopic implantation into bone defects, the released Adv-Cbfa1 accelerated regeneration in the cortical bone, whereas it induced bone resorption in the marrow cavity. A safer gene transfer using a smaller amount of the vector was achieved using biodegradable porous {beta}-TCP as a carrier.

  2. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. PMID:27473985

  3. Low-temperature heat capacities and standard molar enthalpy of formation of 4-(2-aminoethyl)-phenol(C8H11NO)

    Institute of Scientific and Technical Information of China (English)

    Di You-Ying; Kong Yu-Xia; Yang Wei-Wei; Tan Zhi-Cheng

    2008-01-01

    This paper reports that low-temperature heat capacities of 4-(2-aminoethyl)-phenol(C8H11NO)are measured by a precision automated adiabatic calorimeter over the temperature range from 78 to 400 K.A polynomial equation of heat capacities as a function of the temperature was fitted by the least square method.Based on the fitted polynomial,the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated and tabulated at the interval of 5 K.The energy equivalent,gcalor,of the oxygen-bomb The constant-volume energy of combustion of the compound at T=298.15 K was measured by a precision oxygen-bomb combustion and other thermodynamic principles.Finally,the standard molar enthalpy of formation of the compound

  4. A three-dimensional cell-loading system using autologous plasma loaded into a porous {beta}-tricalcium-phosphate block promotes bone formation at extraskeletal sites in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tajima, Nobutaka [Oral and Maxillofacial Surgery, Graduate school, Tokyo Medical and Dental University (Japan); Orthopaedic and Spinal Surgery, Graduate school, Tokyo Medical and Dental University (Japan); Sotome, Shinichi [Orthopaedic and Spinal Surgery, Graduate school, Tokyo Medical and Dental University (Japan); Marukawa, Eriko [Oral and Maxillofacial Surgery, Graduate school, Tokyo Medical and Dental University (Japan); Orthopaedic and Spinal Surgery, Graduate school, Tokyo Medical and Dental University (Japan); Omura, Ken [Oral and Maxillofacial Surgery, Graduate school, Tokyo Medical and Dental University (Japan); Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University (Japan); Shinomiya, Kenichi [Orthopaedic and Spinal Surgery, Graduate school, Tokyo Medical and Dental University (Japan) and Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University (Japan) and Advanced Bone and Joint Science (Japan)]. E-mail: shinomiya.orth@tmd.ac.jp

    2007-05-16

    The effects of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on bone marrow stromal cells (MSCs) with respect to proliferation, osteogenic differentiation, and bone formation capability were investigated. MSCs derived from rats were cultured in medium containing mixtures of PRP and PPP. Fibrinogen was eliminated prior to the experiment. The DNA content and alkaline phosphatase (ALP) activity were measured. PRP stimulated cell proliferation and inhibited osteoblastic differentiation. To examine the effects of fibrin in plasma, MSCs were cultured in PRP or PPP fibrin gels formed both on a cell culture insert installed in a culture well and on the bottom surface of the same culture well. The ALP activities of the MSCs in both of the gels were higher than those on the surface of the culture wells. The MSCs cultured on the PPP gel showed the highest ALP activity. The effects of PRP and PPP used as scaffolds for bone formation were also investigated. MSCs were suspended in PRP or PPP, introduced into porous {beta}-tricalcium phosphate blocks, and then implanted into subcutaneous sites. Subsequently, bone formation was quantified. Further in vivo studies found that implants prepared using PPP had a greater osteoinductive capability than implants prepared with PRP.

  5. A three-dimensional cell-loading system using autologous plasma loaded into a porous β-tricalcium-phosphate block promotes bone formation at extraskeletal sites in rats

    International Nuclear Information System (INIS)

    The effects of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on bone marrow stromal cells (MSCs) with respect to proliferation, osteogenic differentiation, and bone formation capability were investigated. MSCs derived from rats were cultured in medium containing mixtures of PRP and PPP. Fibrinogen was eliminated prior to the experiment. The DNA content and alkaline phosphatase (ALP) activity were measured. PRP stimulated cell proliferation and inhibited osteoblastic differentiation. To examine the effects of fibrin in plasma, MSCs were cultured in PRP or PPP fibrin gels formed both on a cell culture insert installed in a culture well and on the bottom surface of the same culture well. The ALP activities of the MSCs in both of the gels were higher than those on the surface of the culture wells. The MSCs cultured on the PPP gel showed the highest ALP activity. The effects of PRP and PPP used as scaffolds for bone formation were also investigated. MSCs were suspended in PRP or PPP, introduced into porous β-tricalcium phosphate blocks, and then implanted into subcutaneous sites. Subsequently, bone formation was quantified. Further in vivo studies found that implants prepared using PPP had a greater osteoinductive capability than implants prepared with PRP

  6. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate.

    Science.gov (United States)

    Pelletier, Jeffrey C; Lundquist, Joseph T; Gilbert, Adam M; Alon, Nipa; Bex, Frederick J; Bhat, Bheem M; Bursavich, Mattew G; Coleburn, Valerie E; Felix, Luciana A; Green, Daniel M; Green, Paula; Hauze, Diane B; Kharode, Yogendra P; Lam, Ho-Sun; Lockhead, Susan R; Magolda, Ronald L; Matteo, Jeanne J; Mehlmann, John F; Milligan, Colleen; Murrills, Richard J; Pirrello, Jennifer; Selim, Sally; Sharp, Michael C; Unwalla, Ray J; Vera, Matthew D; Wrobel, Jay E; Yaworsky, Paul; Bodine, Peter V N

    2009-11-26

    A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration. PMID:19856966

  7. Optimum potassium chloride concentration to reduce hydration capacity of clay formations; Concentracao otima de cloreto de potassio para reduzir a capacidade de hidratacao das formacoes argilosas

    Energy Technology Data Exchange (ETDEWEB)

    Machado, Jose Carlos Vieira [PETROBRAS, Salvador, BA (Brazil). Centro de Recursos Humanos Norte-Nordeste. Setor de Programas de Perfuracao; Oliveira, Manoel Martins de [PETROBRAS, BA (Brazil). Distrito de Perfuracao. Div. de Tecnicas de Perfuracao

    1988-12-31

    An experimental method for ascertaining the optimal concentration of potassium chloride for reducing the hydration and dispersion capacity of clayey formations sensitive to water-based fluids is described. Under this method, filtering time for disperse systems prepared from clayey formation samples is measured. A discussion is offered on theoretical aspects of hydration, expansion, and dispersion of clayey rocks in response to the variations in stress equilibrium states produced by these phenomena when a hole (well) is opened in the rock. The state of the art of this technological branch is also described. (author) 10 refs., 5 figs., 4 tabs.

  8. Thymidine kinase deficient human cells have increased UV sensitivity in their capacity to support herpes simplex virus but normal UV sensitivity for colony formation

    International Nuclear Information System (INIS)

    A thymidine kinase deficient (tk-) and two thymidine kinase proficient (tk+) human cell lines were compared for UV sensitivity using colony-forming ability as well as their capacity to support the plaque formation of herpes simplex type 1 (HSV-1).The tk- line (143 cells) was a derivative of one of the tk+ lines (R970-5), whereas the other tk+ line (AC4 cells) was a derivative of the 143 cells obtained by transfection with purified sheared HSV-2 DNA encoding the viral tk gene. 143, R970-5 and AC4 cells showed a similar UV sensitivity for colony-forming ability. In contrast, the capacity to support HSV-1 plaque formation immediately (within 1 h) afte UV-irradiation was reduced to a greater extent in the 143 cells compared to the R970-5 and AC4 cells. Capacity curves for plaque formation of the HSV-1: KOS wild-type (tk+) strain were similar to those for the HSV-1: PTK3B mutant (tk-) strain were similar to those for the HSV-1: PTK3B mutant (tk-) strain in the 3 cell strains, indicating that the viral tk gene does not influence the ability of HSV-1 to form plaques in UV-irradiated compared to unirradiated human cells. Cellular capacity for HSV-1 plaque formation was found to recover in both tk- and tk+ cells for cultures infected 24 h after UV-irradiation. These results suggest that repair of UV-damaged DNA takes place to a similar extent in both tk- and tk+ human cells, but the kinetics of repair are initially slower in tk-compared to tk+ human cells. (author). 33 refs.; 3 figs.; 1 tab

  9. Bioengineered periosteal progenitor cell sheets to enhance tendon-bone healing in a bone tunnel

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Chang

    2012-12-01

    Full Text Available Background: Tendon-bone tunnel healing is crucial for long term success in anterior cruciate liga­ment (ACL reconstruction. The periosteum contains osteochondral progenitor cells that can differenti­ate into osteoblasts and chondroblasts during tendon-bone healing. We developed a scaf­fold-free method using polymerized fibrin-coated dishes to make functional periosteal progenitor cell (PPC sheets. Bioengineered PPC sheets for enhancing tendon-bone healing were evaluated in an extra-articular bone tunnel model in rabbit. Methods: PPC derived from rabbit tibia periosteum, cultivated on polymerized fi­brin-coated dishes and harvested as PPC sheet. A confocal microscopy assay was used to evaluate the morphology of PPC sheets. PPC sheets as a periosteum to wrap around hamstring tendon grafts were pulled into a 3-mm diameter bone tunnel of tibia, and compared with a tendon graft without PPC sheets treatment. Rabbits were sacrificed at 4 and 8 weeks postoperatively for biochemical as­say and histological assay to demonstrate the enhancement of PPC sheets in tendon-bone healing. Results: PPC spread deposit on fibrin on the dish surface with continuous monolayer PPC was ob­served. Histological staining revealed that PPC sheets enhance collagen and glycosaminoglycans deposi­tion with fibrocartilage formation in the tendon-bone junction at 4 weeks. Collagen fiber with fibrocartilage formation at tendon-bone junction was also found at 8 weeks. Matured fibrocartilage and dense collagen fiber were formed at the tendon-bone interface at 8 weeks by Masson trichrome and Safranin-O staining Conclusions: Periosteal progenitor cell monolayer maintains the differentiated capacity and osteochon­dral potential in order to promote fibrocartilage formation in tendon-bone junction. Bioengi­neered PPC sheets can offer a new feasible therapeutic strategy of a novel approach to en­hance tendon-bone junction healing.

  10. The history and histology of bone morphogenetic protein.

    Science.gov (United States)

    Murray, Samuel S; Brochmann Murray, Elsa J; Wang, Jeffrey C; Duarte, Maria Eugenia Leite

    2016-07-01

    Bone morphogenetic proteins are a group of structurally related proteins within the TGF-β superfamily of proteins with a diverse repertoire of functions in embryonic and adult organisms. As is apparent from the name, the members first characterized participate in bone growth, development, and remodeling. The "morphogenic" activity per se is defined as the induction of a recapitulation of endochondral bone formation by appropriate stem cells. The regenerative capacity of bone has been recognized since ancient times. The mechanism, applications, and conceptual basis of bone transplantation, bone implantation, ectopic bone formation, and exogenously induced bone formation have been studied by many investigators for more than a century. This review examines the efforts to characterize this activity in the European and American literature over approximately the last century. Because of the inherently complex nature of the process induced by these molecules (inflammation, stem cell proliferation, cartilage differentiation, replacement of cartilage with bone) it is important to evaluate previous investigations through a histological perspective. The cellular basis of the contemporary bioassay for BMP activity is illustrated and discussed from the histological point of view. PMID:26907674

  11. 模拟失重对大鼠承重骨骨髓基质细胞数量及体外成骨能力的影响%Effects of simulated weightlessness on bone marrow stromal cell count and osteogentic capacity of weight bearing bone in rats

    Institute of Scientific and Technical Information of China (English)

    付崇建; 郁冰冰; 杨连甲; 曹新生; 张立藩

    2007-01-01

    背景:骨组织在特殊物理环境如失重环境下,代谢活动会发生显著的变化,而成骨细胞是骨代谢和骨形成的核心部分,其对重力环境的变化敏感.目的:观察模拟失重条件对大鼠股骨骨髓基质细胞数量体外成骨能力的影响,揭示骨丢失的机制.设计:随机配对,对照实验.单位:解放军第四军医大学航空航天医学系和口腔医学院病理科.材料:选用20只成年健康雄性SD大鼠.实验开始当日按体质量随机分为对照组和悬吊组,每组10只.碱性磷酸酶试剂盒由北京中生生物工程高技术公司生产.方法:实验于1999-11/2000-07在解放军第四军医大学口腔医学院病理科完成.将SD大鼠随机配对分为鼠尾悬吊组和对照组,每组10只.悬吊组大鼠做尾部悬吊28 d,大鼠始终保持30°头低位及后肢自由悬垂不负重状态.对照组正常饲养.实验期满,取股骨,将股骨骨髓基质细胞进行原代和传代细胞培养.主要观察指标:采用细胞计数法和噻唑蓝法绘制原代和传代培养细胞的生长曲线,进行碱性磷酸酶活性及体外矿化小结形成量的检测.结果:①碱性磷酸酶活性:原代和传代培养悬吊组低于对照组,差异有显著性意义(P<0.05).②钙化小结形成数:悬吊组少于对照组,差异有显著性意义(P<0.05).③细胞生长:原代和传代股骨间充质细胞的生长曲线呈"S"形,悬吊组和对照组细胞倍增时间相近.④股骨骨髓基质细胞数:原代细胞培养系中,悬吊组比对照组约少50%(P<0.05).结论:模拟失重条件下,大鼠骨髓基质细胞数明显减少,后肢承重骨成骨细胞数减少,体外成骨能力降低.%BACKGROUND: Under specially physical environment, for example weightlessness, metabolism of bone tissue may have remarkable changes; however, osteoblast is a core of bone metabolism and bone formation, so it is very sensitive to changes of gravity environment.OBJECTIVE: To observe the effects

  12. Low-temperature heat capacities and standard molar enthalpy of formation of N-methylnorephedrine C211H17NO(s)

    Institute of Scientific and Technical Information of China (English)

    Di You-Ying; Wang Da-Qi; Shi Quan; Tan Zhi-Cheng

    2008-01-01

    This paper reports that low-temperature heat capacities of N-methylnorephedrine C11H17NO(s) have been mea- sured by a precision automated adiabatic calorimeter over the temperature range from T=78 K to T=400 K. A solid to liquid phase transition of the compound was found in the heat capacity curve in the temperature range of T=342- 364 K. The peak temperature, molar enthalpy and entropy of fusion of the substance were determined. The experimental values of the molar heat capacities in the temperature regions of T=78-342 K and T=364-400 K were fitted to two poly- nomial equations of heat capacities with the reduced temperatures by least squares method. The smoothed molar heat capacities and thermodynamic functions of N-methylnorephedrine C11H17NO(s) relative to the standard refer- ence temperature 298.15 K were calculated based on the fitted polynomials and tabulated with an interval of 5 K. The constant-volume energy of combustion of the compound at T=298.15 K was measured by means of an isoperibol preci- sion oxygen-bomb combustion calorimeter. The standard molar enthalpy of combustion of the sample was calculated. The standard molar enthalpy of formation of the compound was determined from the combustion enthalpy and other auxiliary thermodynamic data through a Hess thermochemical cycle.

  13. Self-assembled Biodegradable Nanoparticles and Polysaccharides as Biomimetic ECM Nanostructures for the Synergistic effect of RGD and BMP-2 on Bone Formation.

    Science.gov (United States)

    Wang, Zhenming; Dong, Li; Han, Lu; Wang, Kefeng; Lu, Xiong; Fang, Liming; Qu, Shuxin; Chan, Chun Wai

    2016-01-01

    Producing biomimetic extracellular matrix (ECM) is an effective approach to improve biocompatibility of medical devices. In this study, biomimetic ECM nanostructures are constructed through layer-by-layer self-assembling positively charged chitosan (Chi), negatively charged oxidized sodium alginate (OAlg), and positively charged bovine serum albumin (BSA)-based nanoparticles. The BSA-based nanoparticles in the self-assembled films not only result in porous nanostructures similar to natural ECM, but also preserve the activity and realize the sustained release of Bone morphogenetic protein-2 (BMP-2). The results of bone marrow stem cells (BMSCs) culture demonstrate that the penta-peptide glycine-arginine-glycine-aspartate-serine (GRGDS) grafted Chi/OAlg films favor cell adhesion and proliferation. GRGDS and BMP-2 in biomimetic ECM nanostructures synergistically promote BMSC functions and new bone formation. The RGD and BMP incorporated biomimetic ECM coatings could be applied on a variety of biomedical devices to improve the bioactivity and biocompatibility. PMID:27121121

  14. Self-assembled Biodegradable Nanoparticles and Polysaccharides as Biomimetic ECM Nanostructures for the Synergistic effect of RGD and BMP-2 on Bone Formation

    Science.gov (United States)

    Wang, Zhenming; Dong, Li; Han, Lu; Wang, Kefeng; Lu, Xiong; Fang, Liming; Qu, Shuxin; Chan, Chun Wai

    2016-01-01

    Producing biomimetic extracellular matrix (ECM) is an effective approach to improve biocompatibility of medical devices. In this study, biomimetic ECM nanostructures are constructed through layer-by-layer self-assembling positively charged chitosan (Chi), negatively charged oxidized sodium alginate (OAlg), and positively charged bovine serum albumin (BSA)-based nanoparticles. The BSA-based nanoparticles in the self-assembled films not only result in porous nanostructures similar to natural ECM, but also preserve the activity and realize the sustained release of Bone morphogenetic protein-2 (BMP-2). The results of bone marrow stem cells (BMSCs) culture demonstrate that the penta-peptide glycine-arginine-glycine-aspartate-serine (GRGDS) grafted Chi/OAlg films favor cell adhesion and proliferation. GRGDS and BMP-2 in biomimetic ECM nanostructures synergistically promote BMSC functions and new bone formation. The RGD and BMP incorporated biomimetic ECM coatings could be applied on a variety of biomedical devices to improve the bioactivity and biocompatibility. PMID:27121121

  15. Radiotherapy of heterotopic bone formation in patients with paraplegia. Preliminary results; Strahlentherapie heterotoper Ossifikationen bei Querschnittsgelaehmten. Praeliminaere Ergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Sautter-Bihl, M.L. [Klinik fuer Strahlentherapie, Staedtisches Klinikum Karlsruhe (Germany); Liebermeister, E. [Klinik fuer Strahlentherapie, Staedtisches Klinikum Karlsruhe (Germany); Heinze, H.G. [Klinik fuer Strahlentherapie, Staedtisches Klinikum Karlsruhe (Germany); Nanassy, A. [Klinik fuer Orthopaedie, Rehabilitationskrankenhaus Langensteinbach (Germany); Stoltze, D. [Klinik fuer Orthopaedie, Rehabilitationskrankenhaus Langensteinbach (Germany)

    1995-08-01

    In 20 patients with paralysis, 25 regions were irradiated with (mostly) 10 Gy in single fractions of 2 to 2.5 Gy using 8 MW photons. In 15 patients radiotherapy was performed as a primary treatment in the status of myositis; 7 patients were treated after (subtotal) resection of already manifest ossifications (2 patients were treated twice, primarily and postoperatively). In a minimum follow-up 12 weeks, none of the 20 irradiated patients showed any progression of the developing or already manifest ossification; thus mobilisation and rehabilitation could be carried out as desired. No side effects occurred. The preliminary results of the present study suggest that radiotherapy is an effective local treatment with minimal side effects for the prevention of heterotopic bone formation in patients with paraplegia. (orig.) [Deutsch] Bei 20 Patienten (18 Maenner, zwei Frauen, Alter 19 bis 62 Jahre) mit Querschnittssyndrom wurden 25 Regionen mit ueberwiegend 10 Gy a 2 bis 2,5 Gy Einzeldosis mit 8-MW-Photonen bestrahlt. Die Radiatio erfolgte bei 15 Patienten als Primaerprophylaxe im entzuendlichen Stadium, bei sieben Patienten sekundaer nach (subtotaler) Resektion von Ossifikationen (zwei Patienten wurden sowohl primaer als auch sekundaer bestrahlt). Bei einer Mindestnachbeobachtungszeit von zwoelf Wochen trat in keinem Fall eine Progression der sich entwickelnden bzw. bereits bestehenden heterotopen Ossifikationen auf: saemtliche Patienten konnten wunschgemaess mobilisiert und im Rahmen ihrer neurologischen Ausfaelle rehabilitiert werden. Nebenwirkungen traten nicht auf. Die vorliegende praeliminaeren Ergebnisse deuten hin, dass die Strahlentherapie eine effektive und nebenwirkungsarme lokale Therapie zur Verhinderung heterotoper Ossifikationen beim Querschnittssyndrom darstellt. (orig.)

  16. Dual function of ERR alpha in breast cancer and bone metastasis formation: implication of VEGF and osteoprotegerin.

    OpenAIRE

    Fradet, Anais; Sorel, Helene; Bouazza, Lamia; Goehrig, Delphine; Depalle, Baptiste; Bellahcene, Akeila; Castronovo, Vincenzo; Follet, Helene; Descotes, Francoise; Aubin, Jane E; Clezardin, Philippe; Bonnelye, Edith

    2011-01-01

    Bone metastasis is a complication occurring in up to 70% of advanced breast cancer patients. The estrogen receptor-related receptor alpha (ERRalpha) has been implicated in breast cancer and bone development, prompting us to examine whether ERRalpha may function in promoting the osteolytic growth of breast cancer cells in bone. In a mouse xenograft model of metastatic human breast cancer, overexpression of wild-type ERRalpha reduced metastasis, whereas overexpression of a dominant negative mut...

  17. Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    OpenAIRE

    Kawai, Mariko; Bessho, Kazuhisa; Maruyama, Hiroki; Miyazaki, Jun-ichi; Yamamoto, Toshio

    2006-01-01

    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.

  18. Betulinic acid synergically enhances BMP2-induced bone formation via stimulating Smad 1/5/8 and p38 pathways

    OpenAIRE

    Choi, Hyuck; Jeong, Byung-Chul; Kook, Min-Suk; Koh, Jeong-Tae

    2016-01-01

    Background Healing of bone defects is a dynamic and orchestrated process that relies on multiple growth factors and cell types. Bone morphogenetic protein 2 (BMP2) is a key growth factor for bone healing, which stimulates mesenchymal stem cells to differentiate into osteoblasts. Betulinic acid (BetA) is a natural pentacyclic triterpenoid from plants. This study aimed to examine combinatory effects of BetA and BMP2 on ectopic bone generation in mice. Results In MC3T3-E1 preosteoblast culture, ...

  19. INCREASING OF EFFICIENCY OF NATURAL GAS COMBUSTION IN STEAM BOILERS OF SMALL AND MEDIUM CAPACITY DUE TO IMPROVED MIXTURE FORMATION

    OpenAIRE

    Gaponenko A. M.; Kagramanova A. A.; Verzilin O. V.

    2014-01-01

    The article presents methods of industrial tests of the of technical device utility model designed for boilers E-1,0-0,9G-3 QL-500, D-721 of small and medium capacity. The research is aimed at improving the efficiency of fuel combustion in the boiler furnaces due to uniform distribution of airflow when supplying it to the boiler burner

  20. Enhanced MC3T3-E1 preosteoblast response and bone formation on the addition of nano-needle and nano-porous features to microtopographical titanium surfaces

    International Nuclear Information System (INIS)

    Micro/nanotopographical modifications on titanium surfaces constitute a new process to increase osteoblast response to enhance bone formation. In this study, we utilized alkali heat treatment at high (SB-AH1) and low temperatures (SB-AH2) to nano-modify sandblasted titanium with microtopographical surfaces. Then, we evaluated the surface properties, biocompatibility and osteogenic capability of SB-AH1 and SB-AH2 in vitro and in vivo, and compared these with conventional sandblast-acid etching (SLA) and Ti control surfaces. SB-AH1 and SB-AH2 surfaces exhibited micro/nanotopographical modifications of nano-needle structures and nano-porous network layers, respectively, compared with the sole microtopographical surface of macro and micro pits on the SLA surface and the relatively smooth surface on the Ti control. SB-AH1 and SB-AH2 showed different roughness and elemental components, but similar wettability. MC3T3-E1 preosteoblasts anchored closely on the nanostructures of SB-AH1 and SB-AH2 surfaces, and these two surfaces more significantly enhanced cell proliferation and alkaline phosphatase (ALP) activity than others, while the SB-AH2 surface exhibited better cell proliferation and higher ALP activity than SB-AH1. All four groups of titanium domes with self-tapping screws were implanted in rabbit calvarial bone models, and these indicated that SB-AH1 and SB-AH2 surfaces achieved better peri-implant bone formation and implant stability, while the SB-AH2 surface achieved the best percentage of bone-implant contact (BIC%). Our study demonstrated that the micro/nanotopographical surface generated by sandblasting and alkali heat treatment significantly enhanced preosteoblast proliferation, ALP activity and bone formation in vitro and in vivo, and nano-porous network topography may further induce better preosteoblast proliferation, ALP activity and BIC%. (paper)

  1. Phantom studies using a high-resolution CT for ex-vivo imaging of degradable magnesium implants and simulated peri-implant bone formation in rabbit tibiae

    International Nuclear Information System (INIS)

    Purpose: Evaluation of the suitability of the high-resolution CT XtremeCT for ex vivo imaging of degradable magnesium implants with simulated peri-implant bone formation in rabbit tibiae and development of a method for calibrating the mass concentration of a magnesium alloy in an implant volume. Materials and Methods: Using specially designed phantoms, degradable magnesium implants of the alloys LAE442, ZEK100, AX30 and MgCa 0.8 %, without coating and with peri-implant bone formation simulated by a coating, as well as rabbit tibiae were scanned. CT numbers and the contrast-to-noise-ratio (CNR) of the studied materials were determined. The visual distinction between implant and coating was evaluated. To calibrate the implant density, exemplary LAE442 pins with different mass concentrations were scanned using a specially constructed phantom. Subsequently, CT numbers corresponding to the appropriate mass concentration were determined. Results: The implants, coating and substantia corticalis showed a similar density. Visual distinction between coating and implant was strongly dependent on the respective magnesium alloy and chosen scan parameter. A CNR of at least 0.2 was required for a distinction between implant and coating. For the mass concentration, a high CT number linearity (R2 = 0.99) throughout the measuring range (1811 - 1273 mg/cm3 LAE442) was found. Conclusion: As expected, the XtremeCT is primarily suitable for the imaging of bone tissue and implants. Good visual distinction of peri-implant bone formation on magnesium implants in an ex vivo phantom model ranges from possible to difficult depending on the bone density and alloy composition. (orig.)

  2. Bone morphogenetic protein-2 functions as a negative regulator in the differentiation of myoblasts, but not as an inducer for the formations of cartilage and bone in mouse embryonic tongue

    Directory of Open Access Journals (Sweden)

    Suzuki Erika

    2011-07-01

    Full Text Available Abstract Background In vitro studies using the myogenic cell line C2C12 demonstrate that bone morphogenetic protein-2 (BMP-2 converts the developmental pathway of C2C12 from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo studies using null mutation mice demonstrate that BMPs inhibit the specification of the developmental fate of myogenic progenitor cells. However, the roles of BMPs in the phases of differentiation and maturation in skeletal muscles have yet to be determined. The present study attempts to define the function of BMP-2 in the final stage of differentiation of mouse tongue myoblast. Results Recombinant BMP-2 inhibited the expressions of markers for the differentiation of skeletal muscle cells, such as myogenin, muscle creatine kinase (MCK, and fast myosin heavy chain (fMyHC, whereas BMP-2 siRNA stimulated such markers. Neither the recombinant BMP-2 nor BMP-2 siRNA altered the expressions of markers for the formation of cartilage and bone, such as osteocalcin, alkaline phosphatase (ALP, collagen II, and collagen X. Further, no formation of cartilage and bone was observed in the recombinant BMP-2-treated tongues based on Alizarin red and Alcian blue stainings. Neither recombinant BMP-2 nor BMP-2 siRNA affected the expression of inhibitor of DNA binding/differentiation 1 (Id1. The ratios of chondrogenic and osteogenic markers relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a house keeping gene were approximately 1000-fold lower than those of myogenic markers in the cultured tongue. Conclusions BMP-2 functions as a negative regulator for the final differentiation of tongue myoblasts, but not as an inducer for the formation of cartilage and bone in cultured tongue, probably because the genes related to myogenesis are in an activation mode, while the genes related to chondrogenesis and osteogenesis are in a silencing mode.

  3. INCREASING OF EFFICIENCY OF NATURAL GAS COMBUSTION IN STEAM BOILERS OF SMALL AND MEDIUM CAPACITY DUE TO IMPROVED MIXTURE FORMATION

    Directory of Open Access Journals (Sweden)

    Gaponenko A. M.

    2014-12-01

    Full Text Available The article presents methods of industrial tests of the of technical device utility model designed for boilers E-1,0-0,9G-3 QL-500, D-721 of small and medium capacity. The research is aimed at improving the efficiency of fuel combustion in the boiler furnaces due to uniform distribution of airflow when supplying it to the boiler burner

  4. Hibiscus sabdariffa extract inhibits in vitro biofilm formation capacity of Candida albicans isolated from recurrent urinary tract infections

    OpenAIRE

    Issam Alshami; Alharbi, Ahmed E

    2014-01-01

    Objective: To explore the prevention of recurrent candiduria using natural based approaches and to study the antimicrobial effect of Hibiscus sabdariffa (H. sabdariffa) extract and the biofilm forming capacity of Candida albicans strains in the present of the H. sabdariffa extract. Methods: In this particular study, six strains of fluconazole resistant Candida albicans isolated from recurrent candiduria were used. The susceptibility of fungal isolates, time-kill curves and biofilm forming ...

  5. Fibrodysplasia ossificans progressiva (FOP): A human genetic disorder of extra-skeletal bone formation, or - How does one tissue become another?

    OpenAIRE

    Shore, Eileen M.

    2012-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic disease in which de novo osteogenesis – a developmental process occurring during embryonic skeletal formation – is induced aberrantly and progressively beginning during early childhood in soft connective tissues. Episodic initiation of spontaneous bone forming lesions occurs over time, affecting a generally predictable sequence of body locations following a pattern similar to that of the developing embryonic skeleton. The het...

  6. Natural processes involved in the formation of Pleistocene bone assemblages in continental South-East Asian caves : the case of the cave of the monk (Chiang Dao Wildlife Sanctuary, Thailand).

    OpenAIRE

    Lenoble, Arnaud; Zeitoun, Valéry; Laudet, Frédéric; Seveau, Arnoult; Doyasa, Tasana

    2006-01-01

    A large paleontological assemblage typical of Ailuropoda-Stegodon fauna was discovered in the Cave of the Monk, in northern Thailand. Geological and taphonomic approaches were conducted in order to determine site formation processes. A sedimentological study indicated that the fossiliferous layer resulted from mediumsize burrowing animals occupying the cave. Bone surface analysis confirmed that Porcupine was the main, if not exclusive, bone accumulator. A bone accumulation rate was calculated...

  7. Controlled release of simvastatin from in situ forming hydrogel triggers bone formation in MC3T3-E1 cells.

    Science.gov (United States)

    Park, Yoon Shin; David, Allan E; Park, Kyung Min; Lin, Chia-Ying; Than, Khoi D; Lee, Kyuri; Park, Jun Beom; Jo, Inho; Park, Ki Dong; Yang, Victor C

    2013-04-01

    Simvastatin (SIM), a drug commonly administered for the treatment of hypercholesterolemia, has been recently reported to induce bone regeneration/formation. In this study, we investigated the properties of hydrogel composed of gelatin-poly(ethylene glycol)-tyramine (GPT) as an efficient SIM delivery vehicle that can trigger osteogenic differentiation. Sustained delivery of SIM was achieved through its encapsulation in an injectable, biodegradable GPT-hydrogel. Cross-linking of the gelatin-based GPT-hydrogel was induced by the reaction of horse radish peroxidase and H(2)O(2). GPT-hydrogels of three different matrix stiffness, 1,800 (GPT-hydrogel1), 5,800 (GPT-hydrogel2), and 8,400 Pa (GPT-hydrogel3) were used. The gelation/degradation time and SIM release profiles of hydrogels loaded with two different concentrations of SIM, 1 and 3 mg/ml, were also evaluated. Maximum swelling times of GPT-hydrogel1, GPT-hydrogel2, and GPT-hydrogel3 were observed to be 6, 12, and 20 days, respectively. All GPT-hydrogels showed complete degradation within 55 days. The in vitro SIM release profiles, investigated in PBS buffer (pH 7.4) at 37°C, exhibited typical biphasic release patterns with the initial burst being more rapid with GPT-hydrogel1 compared with GPT-hydrogel3. Substantial increase in matrix metalloproteinase-13, osteocalcin expression levels, and mineralization were seen in osteogenic differentiation system using MC3T3-E1 cells cultured with GPT-hydrogels loaded with SIM in a dose-dependent manner. This study demonstrated that controlled release of SIM from a biodegradable, injectable GPT-hydrogel had a promising role for long-term treatment of chronic degenerative diseases such as disc degenerative disease. PMID:23250670

  8. Fracture-fluid relationships: implications for the sealing capacity of clay layers - Insights from field study of the Blue Clay formation, Maltese islands

    International Nuclear Information System (INIS)

    Sealing capacity of clay layers is a key parameter in many fields of geoscience, such as CO2 storage, hydrocarbons trapping, and waste disposal. In the context of deep geological disposal of radioactive waste, clayey formations are studied as potential host rocks. This work deals with tectonic fracturing, fluid flow, and the sealing capacity of clay layers in an outcropping formation sharing similarities to these potential host rocks. The Blue Clay formation (Maltese islands) outcrops between two limestones affected by slight extensional tectonics. Zones of oxidation around fractures are interpreted as evidence of palaeo-fluid circulation, and are used to assess the role of joints and faults in controlling the hydrological communication between adjacent layers. Joints and small faults (displacement 50 m) display clay smear structures, and the lack of oxidized zones around them suggests they served as barriers to fluid flow. Intermediate-sized faults die out up-section into complex deformation zones comprised of irregular joints that are filled with gypsum and surrounded by oxidation zones. These observations indicate that these intermediate-sized faults, usually considered as sealed by classical predictive methods such as 'Shale Smear Factor', may have played a significant role in the local palaeo-hydrology. (authors)

  9. Performance evaluation of multilevel modulation formats using partial response for capacity upgrade in access network with limited electronic bandwidth

    Science.gov (United States)

    Madsen, Peter; Frejstrup Suhr, Lau; Sebastian Rodriguez, Juan; Tafur Monroy, Idelfonso; Vegas Olmos, Juan José

    2016-09-01

    We present a successful experimental evaluation of 4 level Pulse Amplitude Modulation (4-PAM) and Duobinary modulation. An experimental performance evaluation is presented for Duobinary 4 PAM and other modulation formats. All modulation formants used, may be considered to be implemented in future Passive Optical Network (PON) class access networks with limited electrical bandwidth. We compared NRZ, Duobinary, 4-PAM and Duobinary 4-PAM operating at 9 Gbaud over 20 km single mode fiber. The results provides an insight and guidelines on the utilization of these advanced modulation formats.

  10. Hibiscus sabdariffa extract inhibits in vitro biofilm formation capacity of Candida albicans isolated from recurrent urinary tract infections

    Institute of Scientific and Technical Information of China (English)

    Issam Alshami; Ahmed E Alharbi

    2014-01-01

    Objective: To explore the prevention of recurrent candiduria using natural based approaches and to study the antimicrobial effect of Hibiscus sabdariffa (H. sabdariffa) extract and the biofilm forming capacity of Candida albicans strains in the present of the H. sabdariffa extract.Methods:In this particular study, six strains of fluconazole resistant Candida albicans isolated from recurrent candiduria were used. The susceptibility of fungal isolates, time-kill curves and biofilm forming capacity in the present of the H. sabdariffa extract were determined. Results: Various levels minimum inhibitory concentration of the extract were observed against all the isolates. Minimum inhibitory concentration values ranged from 0.5 to 2.0 mg/mL. Time-kill experiment demonstrated that the effect was fungistatic. The biofilm inhibition assay results showed that H. sabdariffa extract inhibited biofilm production of all the isolates. Conclusions: The results of the study support the potential effect of H. sabdariffa extract for preventing recurrent candiduria and emphasize the significance of the plant extract approach as a potential antifungal agent.

  11. Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive Gs–G protein signaling in osteoblasts

    International Nuclear Information System (INIS)

    G protein-coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active Gs-coupled GPCR, under the control of the 2.3 kb Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone of femurs. Here, we further evaluated the effects of enhanced Gs signaling in OBs on intramembranous bone formation by examining calvariae of 1- and 9-week-old Col1(2.3)/Rs1 mice and characterized the in vivo gene expression specifically occurring in osteoblasts with activated Gs G protein-coupled receptor signaling, at the cellular level rather than in a whole bone. Rs1 calvariae displayed a dramatic increase in bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space while Osteocalcin was expressed predominantly in cells along bone surfaces, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb Col I promoter could influence early OB commitment, differentiation, and/or proliferation. Gene expression analysis of calvarial OBs revealed that genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. The set of Gs-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of Gs signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to Gs signaling in mature OBs. - Highlights: • OB expression of an engineered Gs-coupled receptor dramatically increases bone mass. • We investigated the changes in gene expression in vivo in enhanced OB Gs signaling. • Genes in cell cycle and transcription were increased in enhanced OB Gs signaling. • GPCRs and paracrine

  12. Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive G{sub s}–G protein signaling in osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wattanachanya, Lalita, E-mail: lalita_md@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok (Thailand); Wang, Liping, E-mail: lipingwang05@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Millard, Susan M., E-mail: susan.millard@mater.uq.edu.au [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Lu, Wei-Dar, E-mail: weidar_lu@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); O’Carroll, Dylan, E-mail: dylancocarroll@gmail.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Hsiao, Edward C., E-mail: Edward.Hsiao@ucsf.edu [Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA (United States); Conklin, Bruce R., E-mail: bconklin@gladstone.ucsf.edu [Gladstone Institute of Cardiovascular Disease, San Francisco, CA (United States); Department of Medicine, University of California, San Francisco, CA (United States); Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA (United States); Nissenson, Robert A., E-mail: Robert.Nissenson@ucsf.edu [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States)

    2015-05-01

    G protein-coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active G{sub s}-coupled GPCR, under the control of the 2.3 kb Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone of femurs. Here, we further evaluated the effects of enhanced G{sub s} signaling in OBs on intramembranous bone formation by examining calvariae of 1- and 9-week-old Col1(2.3)/Rs1 mice and characterized the in vivo gene expression specifically occurring in osteoblasts with activated G{sub s} G protein-coupled receptor signaling, at the cellular level rather than in a whole bone. Rs1 calvariae displayed a dramatic increase in bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space while Osteocalcin was expressed predominantly in cells along bone surfaces, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb Col I promoter could influence early OB commitment, differentiation, and/or proliferation. Gene expression analysis of calvarial OBs revealed that genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. The set of G{sub s}-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of G{sub s} signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to G{sub s} signaling in mature OBs. - Highlights: • OB expression of an engineered G{sub s}-coupled receptor dramatically increases bone mass. • We investigated the changes in gene expression in vivo in enhanced OB G{sub s} signaling. • Genes in cell cycle and transcription were increased in

  13. Bone tumor

    Science.gov (United States)

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

  14. Bone Grafts

    Science.gov (United States)

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  15. An X-Ray diffraction (XRD) study to characterize the mineralogy of dinosaur bones from Arcillas de Morella Formation

    OpenAIRE

    Piga, Giampaolo; Santos Cubedo, Andrés; Piccinini, Massimo; Enzo, Stefano

    2012-01-01

    An investigation by powder X-ray Diffraction (XRD), supplemented with the Rietveld analysis, was conducted on twenty-two Spanish dinosaur bone specimens from Lower Cretaceous age to investigate mineralogy, taphonomy and diagenetic processes. The diffraction approach assessed in all specimens the presence of fluorapatite at various levels of percentage as the mineral phase constituting the fossil bone. In addition to fluorapatite, calcite and quartz were also found as main se...

  16. Long-term changes in the hormonal regulation of the bone tissue formation and resorption in participants of Chernobyl accident clean-up with high radiation exposure doses. Communication 2

    International Nuclear Information System (INIS)

    Systemic hormonal shifts, which can influence the processes of formation and resorption of the bone tissue both in the direction of osteopenic syndrome and normal bone mineral density are present in the participants of Chernobyl accident clean-up with a high exposure doses at long terms of the accident. Increased aging of the bone tissue in the participants of the clean-up vs the male population of Ukraine was revealed. The state of bone mineral density does not depend of the absorbed dose, age, and the concentration of the studied hormones

  17. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

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

  18. Protein-containing nutrient supplementation following strength training enhances the effect on muscle mass, strength, and bone formation in postmenopausal women

    DEFF Research Database (Denmark)

    Holm, Lars; Olesen, Jens L; Matsumoto, Keitaro;

    2008-01-01

    We evaluated the response of various muscle and bone adaptation parameters with 24 wk of strength training in healthy, early postmenopausal women when a nutrient supplement (protein, carbohydrate, calcium, and vitamin D) or a placebo supplement (a minimum of energy) was ingested immediately...... following each training session. At inclusion, each woman was randomly and double-blindedly assigned to a nutrient group or a placebo (control) group. Muscle hypertrophy was evaluated from biopsies, MRI, and dual-energy X-ray absorptiometry (DEXA) scans, and muscle strength was determined in a dynamometer...... nutrient supplementation results in superior improvements in muscle mass, muscle strength, femoral neck BMD, and bone formation during 24 wk of strength training. The observed differences following such a short intervention emphasize the significance of postexercise nutrient supply on musculoskeletal...

  19. Functionalisation of PLLA nanofiber scaffolds using a possible cooperative effect between collagen type I and BMP-2: impact on colonization and bone formation in vivo.

    Science.gov (United States)

    Schofer, Markus D; Tünnermann, Lisa; Kaiser, Hendric; Roessler, Philip P; Theisen, Christina; Heverhagen, Johannes T; Hering, Jacqueline; Voelker, Maximilian; Agarwal, Seema; Efe, Turgay; Fuchs-Winkelmann, Susanne; Paletta, Jürgen R J

    2012-09-01

    The reconstruction of large bone defects after injury or tumor resection often requires the use of bone substitution. Artificial scaffolds based on synthetic biomaterials can overcome disadvantages of autologous bone grafts, like limited availability and donor side morbidity. Among them, scaffolds based on nanofibers offer great advantages. They mimic the extracellular matrix, can be used as a carrier for growth factors and allow the differentiation of human mesenchymal stem cells. Differentiation is triggered by a series of signaling processes, including integrin and bone morphogenetic protein (BMP), which act in a cooperative manner. The aim of this study was to analyze whether these processes can be remodeled in artificial poly-(l)-lactide acid (PLLA) based nanofiber scaffolds in vivo. Electrospun matrices composed of PLLA-collagen type I or BMP-2 incorporated PLLA-collagen type I were implanted in calvarial critical size defects in rats. Cranial CT-scans were taken 4, 8 and 12 weeks after implantation. Specimens obtained after euthanasia were processed for histology and immunostainings on osteocalcin, BMP-2 and Smad5. After implantation the scaffolds were inhomogeneously colonized and cells were only present in wrinkle- or channel-like structures. Ossification was detected only in focal areas of the scaffold. This was independent of whether BMP-2 was incorporated in the scaffold. However, cells that migrated into the scaffold showed an increased ratio of osteocalcin and Smad5 positive cells compared to empty defects. Furthermore, in case of BMP-2 incorporated PLLA-collagen type I scaffolds, 4 weeks after implantation approximately 40 % of the cells stained positive for BMP-2 indicating an autocrine process of the ingrown cells. These findings indicate that a cooperative effect between BMP-2 and collagen type I can be transferred to PLLA nanofibers and furthermore, that this effect is active in vivo. However, this had no effect on bone formation. The reason for

  20. Standard partial molar heat capacities and enthalpies of formation of aqueous aluminate under hydrothermal conditions from integral heat of solution measurements

    International Nuclear Information System (INIS)

    Highlights: • Heats of solution of NaAlO2(s) were measured at five temperatures up to 250 °C. • Standard molar enthalpies of solution were determined from the measured heats of solution. • Standard molar enthalpies of solution were correlated with the density model. • The density model allows us to determine the standard molar heat capacities of reaction. - Abstract: Heats of solution of sodium aluminum oxide, NaAlO2(s), were measured in aqueous sodium hydroxide solutions using a Tian–Calvet heat-flow calorimeter (Setaram, Model C80) with high pressure “batch cells” made of hastelloy C-276, at five temperatures from (373.15 to 523.15) K, steam saturation pressure, and concentrations from (0.02 to 0.09) mol · kg−1. Standard molar enthalpies of solution, ΔsolnH∘, and relative standard molar enthalpies, [H∘(T) − H∘(298.15 K)], of NaAl(OH)4(aq) were determined from the measured heats of solution. The results were fitted with the “density” model. The temperature dependence of ΔsolnH∘ from the model yielded the standard molar heat capacities of reaction, ΔsolnCp∘, from which standard partial molar heat capacities for aqueous aluminate, Cp∘[A1(OH)4−,aq], were calculated. Standard partial molar enthalpies of formation, ΔfH∘, and entropies, S∘, of A1(OH)4−(aq) were also determined. The values for Cp∘[A1(OH)4−,aq] agree with literature data determined up to T = 413 K from enthalpy of solution and heat capacity measurements to within the combined experimental uncertainties. They are consistent with differential heat capacity measurements up to T = 573 K from Schrödle et al. (2010) [29] using the same calorimeter, but this method has the advantage that measurements could be made at much lower concentrations in the presence of an excess concentration of ligand. To our knowledge, these are the first standard partial molar heat capacities measured under hydrothermal conditions by the integral heat of solution method in a

  1. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo

    Science.gov (United States)

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-04-01

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01439e

  2. Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LI Cai-juan; GUO Su-fen; SHI Tie-mei

    2012-01-01

    Background Parthenolide has been tested for anti-tumor activities,such as anti-proliferation and pro-apoptosis in recent studies.However,little is known about its role in the process of tumor angiogenesis.This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation,migration and lumen formation capacity of human umbilical vein endothelial cells.Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells.After 24-hour incubation,the culture supematants were harvested and used to treat human umbilical vein endothelial cells for 24 hours.Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells.The secretion of vascular endothelial growth factor (VEGF),interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.Results Suppression of proliferation,migration,and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide.Parthenolide decreased the levels of the angiogenic factors MMP-9,VEGF,and IL-8secreted by the MDA-MB-231 cells.Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation,migration and lumen-like structure formation of endothelial cells,thereby inhibiting tumor growth.It is a promising potential anti-angiogenic drug.

  3. [Morphological analysis of bone dynamics and metabolic bone disease. Histomorphometric concepts of bone remodeling and modeling].

    Science.gov (United States)

    Takahashi, Hideaki E

    2011-04-01

    In tissue level turnover of bone cells, bone remodeling shows a sequential events of activation, resorption, reversal and formation. This may be observed as secondary osteons in the cortical bone and trabecular packets in the cancellous bone. Microcracks are repaired by targeted remodeling, and calcium is released by non-targeted remodeling. In macromodeling, a macroscopic size of a bone increases with growth, without changing its basic figure. In micromodelimg, a shift of trabecula, a minishift, is biomechnically controlled. New lamellar bone is added parallel to compressive and tensile force, and bone resorption occurs at the opposite surface of formation. In minimodeling new lamellar bone is formed with a sequence of activation, then directly formation, without scalloping at the cement line between newly formed bone and its basic bone. PMID:21447918

  4. Fish bone as a nidus for stone formation in the common bile duct: report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwan; Lee, Sang Kwon; Kwon, Jung Hyeok; Woo, Seong Ku [Dongsan Medical Center, Keimyung University College of Medicine, Daegu (Korea, Republic of); Kim, Yong Joo [Andong General Hospital, Andong (Korea, Republic of); Park, Won Kyu [Youngnam University Hospital, Daegu (Korea, Republic of)

    2004-09-15

    We report two cases of common bile duct stone formed around a fish bone which migrated from the intestinal tract, along with their characteristic imaging findings. Two patients who had no history of previous operation were admitted because of cholangitis. Percutaneous transhepatic biliary drainage (PTBD) was performed and the cholangiogram showed filling defects with an unusually elongated shape in the common bile duct. After improvement of the cholangitic symptoms, the stones were removed through the PTBD tract under fluoroscopic guidance. A nidus consisting of a 1.5 cm sized fish bone was found in each stone removed.

  5. Magnesium substitution in brushite cements for enhanced bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Cabrejos-Azama, Jatsue, E-mail: jacaza@farm.ucm.es [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); Alkhraisat, Mohammad Hamdan; Rueda, Carmen [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain); Torres, Jesús [Facultad de Ciencias de la salud URJC, Alcorcón, Madrid (Spain); Blanco, Luis [Departamento de Estomatología III, Facultad de Odontología UCM, Madrid (Spain); López-Cabarcos, Enrique [Departamento de Química-Física II, Facultad de Farmacia, UCM, Madrid (Spain)

    2014-10-01

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p < 0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. - Highlights: • The Mg-CPCs promote higher new bone formation than the CPC. • The incorporation of magnesium ions in CPC improves osteoblasts proliferation. • Mg-CPC is a bone substitute with controllable biodegradable properties. • We suggest that the use of Mg ions could improve the clinical efficiency of CPCs.

  6. Magnesium substitution in brushite cements for enhanced bone tissue regeneration

    International Nuclear Information System (INIS)

    We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p < 0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations. - Highlights: • The Mg-CPCs promote higher new bone formation than the CPC. • The incorporation of magnesium ions in CPC improves osteoblasts proliferation. • Mg-CPC is a bone substitute with controllable biodegradable properties. • We suggest that the use of Mg ions could improve the clinical efficiency of CPCs

  7. Analyses of stable isotopes in camelids collagen bones from Tulan Ravine, Atacama Puna, early formative period (CA 3,1000-2,400BP)

    International Nuclear Information System (INIS)

    This paper presents the results of isotope analysis (δ13C y δ15N) conducted on bone collagen found in Lama guanicoe and Lama glama remains from Tulan-85 and Tulan-54 archaeological sites. Both sites have been dated to the Early Formative Period (ca. 3,100-2,400 ap) and are located southeast of the Atacama Puna basin. Faunal samples were selected using anatomical and morphometric criteria. The results indicate divergences in the diets of both species, reflecting vegetation variation in the Tulan Quebrada caused by altitude differences and linked to hunting and herding areas

  8. Bioactive polyphenol interactions with β amyloid: a comparison of binding modelling, effects on fibril and aggregate formation and neuroprotective capacity.

    Science.gov (United States)

    Das, Sukanya; Stark, Lina; Musgrave, Ian F; Pukala, Tara; Smid, Scott D

    2016-02-01

    In this study we compared the effects of a diverse set of natural polyphenolics ligands on in silico interactive modelling, in vitro anti-aggregative properties and neuronal toxicity of β amyloid. The β amyloid-binding characteristics of optimised structural conformations of polyphenols with ascribed neuroprotective actions including punicalagin, myricetin, luteolin and honokiol were determined in silico. Thioflavin T and transmission electron microscopy were used to assess in vitro inhibitory effects of these polyphenols on Aβ1-42 fibril and aggregation formation. Phaeochromocytoma (PC12) cells were exposed to Aβ1-42, alone and in combination with test concentrations of each polyphenol (100 μM) and viability measured using MTT assay. Aβ1-42 evoked a concentration-dependent loss of cell viability in PC12 cells, in which all four polyphenols demonstrated significant inhibition of neurotoxicity. While all compounds variably altered the morphology of Aβ aggregation, the flavonoids luteolin and myricetin and the lignan honokiol all bound in a similar hydrophobic region of the amyloid pentamer and exerted the most pronounced inhibition of Aβ1-42 aggregation. Each of the polyphenols demonstrated neuroprotective effects in PC12 cells exposed to Aβ1-42, including punicalagin. These findings highlight some structure-activity insights that can be gleaned into the anti-aggregatory properties of bioactive polyphenols based on modelling of their binding to β-amyloid, but also serve to highlight the more general cellular neuroprotective nature of such compounds. PMID:26815043

  9. PENGGUNAAN BONE GRAFT PADA PERAWATAN KERUSAKAN TULANG PERIODONTAL (Used Bone Graft for Periodontal Defect Treatment)

    OpenAIRE

    Elly Munadziroh; Mohamad Rubianto; Asti Meizarini

    2015-01-01

    Generally the signs and symptoms of advances periodontal disease are periodontal pockets formation to alveolar bone defect. Bone defect treated with placement a preparation material to promote new bone formation. Tissue transplantation were developed, to recontsruct bone defect with the placement of bone graft material. This paper will discuss the used of demineralied freeze dried bone allograft (DFDBA) and anorganic bone mineral combined with synthetic 15 amino acid sequence within type I co...

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

    OpenAIRE

    2015-01-01

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

  11. Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging.

    Science.gov (United States)

    Gao, Guifang; Yonezawa, Tomo; Hubbell, Karen; Dai, Guohao; Cui, Xiaofeng

    2015-10-01

    Inkjet bioprinting is one of the most promising additive manufacturing approaches for tissue fabrication with the advantages of high speed, high resolution, and low cost. The limitation of this technology is the potential damage to the printed cells and frequent clogging of the printhead. Here we developed acrylated peptides and co-printed with acrylated poly(ethylene glycol) (PEG) hydrogel with simultaneous photopolymerization. At the same time, the bone marrow-derived human mesenchymal stem cells (hMSCs) were precisely printed during the scaffold fabrication process so the cells were delivered simultaneously with minimal UV exposure. The multiple steps of scaffold synthesis and cell encapsulation were successfully combined into one single step using bioprinting. The resulted peptide-conjugated PEG scaffold demonstrated excellent biocompatibility, with a cell viability of 87.9 ± 5.3%. Nozzle clogging was minimized due to the low viscosity of the PEG polymer. With osteogenic and chondrogenic differentiation, the bioprinted bone and cartilage tissue demonstrated excellent mineral and cartilage matrix deposition, as well as significantly increased mechanical properties. Strikingly, the bioprinted PEG-peptide scaffold dramatically inhibited hMSC hypertrophy during chondrogenic differentiation. Collectively, bioprinted PEG-peptide scaffold and hMSCs significantly enhanced osteogenic and chondrogenic differentiation for robust bone and cartilage formation with minimal printhead clogging. PMID:25641582

  12. Bone Biopsy

    Science.gov (United States)

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

  13. Experimental Study on Low Intensity Ultrasound and Tissue Engineering to Repair Segmental Bone Defects

    Institute of Scientific and Technical Information of China (English)

    YE Fagang; XIA Changsuo; XIA Renyun

    2006-01-01

    In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were established and randomly divided into 2 groups. All defects were implanted with the composite of calcium phosphate cement and bone mesenchymal stem cells, and additionally those in experimental group were subjected to low intensity ultrasound exposure, while those in control group to sham exposure. The animals were killed on the postoperative week 4, 8 and 12 respectively, and specimens were harvested. By using radiography and the methods of biomechanics, histomorphology and bone density detection, new bone formation and material degradation were observed. The results showed that with the prolongation of time after operation, serum alkaline phosphatase (AKP) levels in both groups were gradually increased, especially in experimental group,reached the peak at 6th week (experimental group: 1.26 mmol/L; control group: 0.58 mmol/L), suggesting the new bone formation in both two group, but the amount of new bone formation was greater and bone repairing capacity stronger in experimental group than in control group. On the 4th week in experimental group, chondrocytes differentiated into woven bone, and on the 12th week, remodeling of new lamellar bone and absorption of the composite material were observed. The mechanical strength of composite material and new born density in experimental group were significantly higher than in control group, indicating that low intensity ultrasound could not only effectively increase the formation of new bone, but also accelerate the calcification of new bone. It was concluded that low intensity ultrasound could evidently accelerate the healing of bone defects repaired by bone tissue engineering.

  14. Facile formation of a Li3PO4 coating layer during the synthesis of a lithium-rich layered oxide for high-capacity lithium-ion batteries

    Science.gov (United States)

    Lee, Yongho; Lee, Jieun; Lee, Kwan Young; Mun, Junyoung; Lee, Joong Kee; Choi, Wonchang

    2016-05-01

    The facile surface modification of transition-metal hydroxide precursors with ammonium dihydrogen phosphate was performed by ball-milling before the calcination process. The prepared precursors were mixed with the required amount of lithium hydroxide and then simply calcined to obtain lithium-phosphate-coated lithium transition metal oxide cathodes during the one-pot calcination process. A thin, homogeneous Li3PO4 coating is firstly formed on the surface of the precursor owing to the abundance of lithium at a lower-temperature range, and subsequent formation of lithium transition metal oxide is achieved at a higher-temperature range during the calcination process. The Li3PO4-coated cathode electrode with the high loading level over 12 mg cm-1 exhibits a discharge capacity of 106 mAh g-1 at 5C at ambient temperature. Furthermore, it delivers 90% capacity retention after 50 cycles at 60 °C.

  15. In vitro expanded bone marrow-derived murine (C57Bl/KaLwRij) mesenchymal stem cells can acquire CD34 expression and induce sarcoma formation in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Song [Department of Lung Cancer Surgery, Lung Cancer Institute, Tianjin Medical University General Hospital, 300052 Tianjin (China); Stem Cell Laboratory-Division Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels (Belgium); Department of Hematology and Immunology, Vrije Universiteit Brussel (VUB)-Myeloma Center, Laarbeeklaan 103, 1090 Brussels (Belgium); De Becker, Ann [Stem Cell Laboratory-Division Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels (Belgium); De Raeve, Hendrik [Department of Anatomopathology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels (Belgium); Van Camp, Ben; Vanderkerken, Karin [Department of Hematology and Immunology, Vrije Universiteit Brussel (VUB)-Myeloma Center, Laarbeeklaan 103, 1090 Brussels (Belgium); Van Riet, Ivan, E-mail: ivan.vanriet@uzbrussel.be [Stem Cell Laboratory-Division Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels (Belgium); Department of Hematology and Immunology, Vrije Universiteit Brussel (VUB)-Myeloma Center, Laarbeeklaan 103, 1090 Brussels (Belgium)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Murine MSCs can undergo spontaneously malignant transformation and form sarcoma. Black-Right-Pointing-Pointer Acquisition of CD34 is a transformation type for MSCs into sarcoma. Black-Right-Pointing-Pointer Notch/Hh/Wnt pathways are related to the malignant phenotype of transformed MSCs. -- Abstract: Mesenchymal stem cells (MSCs) have currently generated numerous interests in pre-clinical and clinical applications due to their multiple lineages differentiation potential and immunomodulary effects. However, accumulating evidence indicates that MSCs, especially murine MSCs (mMSCs), can undergo spontaneous transformation after long-term in vitro culturing, which might reduce the therapeutic application possibilities of these stem cells. In the present study, we observed that in vitro expanded bone marrow (BM) derived mMSCs from the C57Bl/KaLwRij mouse strain can lose their specific stem cells markers (CD90 and CD105) and acquire CD34 expression, accompanied with an altered morphology and an impaired tri-lineages differentiation capacity. Compared to normal mMSCs, these transformed mMSCs exhibited an increased proliferation rate, an enhanced colony formation and migration ability as well as a higher sensitivity to anti-tumor drugs. Transformed mMSCs were highly tumorigenic in vivo, resulting in aggressive sarcoma formation when transplanted in non-immunocompromised mice. Furthermore, we found that Notch signaling downstream genes (hey1, hey2 and heyL) were significantly upregulated in transformed mMSCs, while Hedgehog signaling downstream genes Gli1 and Ptch1 and the Wnt signaling downstream gene beta-catenin were all decreased. Taken together, we observed that murine in vitro expanded BM-MSCs can transform into CD34 expressing cells that induce sarcoma formation in vivo. We assume that dysregulation of the Notch(+)/Hh(-)/Wnt(-) signaling pathway is associated with the malignant phenotype of the transformed mMSCs.

  16. In vitro expanded bone marrow-derived murine (C57Bl/KaLwRij) mesenchymal stem cells can acquire CD34 expression and induce sarcoma formation in vivo

    International Nuclear Information System (INIS)

    Highlights: ► Murine MSCs can undergo spontaneously malignant transformation and form sarcoma. ► Acquisition of CD34 is a transformation type for MSCs into sarcoma. ► Notch/Hh/Wnt pathways are related to the malignant phenotype of transformed MSCs. -- Abstract: Mesenchymal stem cells (MSCs) have currently generated numerous interests in pre-clinical and clinical applications due to their multiple lineages differentiation potential and immunomodulary effects. However, accumulating evidence indicates that MSCs, especially murine MSCs (mMSCs), can undergo spontaneous transformation after long-term in vitro culturing, which might reduce the therapeutic application possibilities of these stem cells. In the present study, we observed that in vitro expanded bone marrow (BM) derived mMSCs from the C57Bl/KaLwRij mouse strain can lose their specific stem cells markers (CD90 and CD105) and acquire CD34 expression, accompanied with an altered morphology and an impaired tri-lineages differentiation capacity. Compared to normal mMSCs, these transformed mMSCs exhibited an increased proliferation rate, an enhanced colony formation and migration ability as well as a higher sensitivity to anti-tumor drugs. Transformed mMSCs were highly tumorigenic in vivo, resulting in aggressive sarcoma formation when transplanted in non-immunocompromised mice. Furthermore, we found that Notch signaling downstream genes (hey1, hey2 and heyL) were significantly upregulated in transformed mMSCs, while Hedgehog signaling downstream genes Gli1 and Ptch1 and the Wnt signaling downstream gene beta-catenin were all decreased. Taken together, we observed that murine in vitro expanded BM-MSCs can transform into CD34 expressing cells that induce sarcoma formation in vivo. We assume that dysregulation of the Notch(+)/Hh(−)/Wnt(−) signaling pathway is associated with the malignant phenotype of the transformed mMSCs.

  17. New, fast corroding high ductility Mg–Bi–Ca and Mg–Bi–Si alloys, with no clinically observable gas formation in bone implants

    International Nuclear Information System (INIS)

    Highlights: ► Biodegradable, biocompatible and highly ductile Mg alloys based on the Mg–Bi system have been produced by rapid solidification and extrusion processes. ► The implants corroded fast within the first 4 weeks after implantation in rabbit bone, but no gas formation has been clinically observed. ► The corrosion rate could be significantly reduced in vitro and in vivo by using high purity magnesium for the alloy production. - Abstract: Current approaches to initial corrosion rate reduction of biodegradable magnesium alloys include alloying with rare earth elements, mechanical processing, coatings and the use of metallic glasses. The latter has limited ductility needed for implant adaptively to various surgery procedures. Furthermore, slow corroding magnesium alloys, coatings or metallic glasses have not proved to be fully dissolvable in vivo. With this in mind, we have developed a new class of biocompatible, biodegradable ductile magnesium alloys with 40% elongation at room temperature. The alloys are based on the Mg–Bi system and undergo a series of production routes, which include rapid solidification (RS) and various extrusion processes. The Mg–Bi–Si (B-BS) system exhibited a high corrosion rates in vitro and was excluded from in vivo screening. In preliminary experiments of Mg–Bi–Ca (B-BX) in rabbit femur bones, the alloy corroded rapidly without any clinically visible gas formation. Only 30% of the B-BX implant remained uncorroded after 4 weeks of implantation. After using low iron Mg for implant preparation the corrosion rate of HP-B-BX was reduced in bone leaving 70% of the implant uncorroded after 4 weeks, while the corrosion in intramuscular and subcutaneous sites were still high leaving only 40% and 10% uncorroded after 4 weeks. The foreign body reaction was very mild and enhanced bone formation could be observed in the vicinity of the corroding implant. Thus, these new magnesium alloys are potentially promising biomaterials

  18. New, fast corroding high ductility Mg-Bi-Ca and Mg-Bi-Si alloys, with no clinically observable gas formation in bone implants

    Energy Technology Data Exchange (ETDEWEB)

    Remennik, S., E-mail: saggym@gmail.com [Department of Materials Engineering, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Bartsch, I.; Willbold, E.; Witte, F. [Laboratory for Biomechanics and Biomaterials, Orthopaedic Clinic, Hannover Medical School, Anna-von-Borries-Str. 1-7, 30625 Hannover (Germany); Shechtman, D. [Department of Materials Engineering, Technion-Israel Institute of Technology, Haifa 32000 (Israel); MSE, Iowa State University, Ames, Iowa 50011 (United States)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer Biodegradable, biocompatible and highly ductile Mg alloys based on the Mg-Bi system have been produced by rapid solidification and extrusion processes. Black-Right-Pointing-Pointer The implants corroded fast within the first 4 weeks after implantation in rabbit bone, but no gas formation has been clinically observed. Black-Right-Pointing-Pointer The corrosion rate could be significantly reduced in vitro and in vivo by using high purity magnesium for the alloy production. - Abstract: Current approaches to initial corrosion rate reduction of biodegradable magnesium alloys include alloying with rare earth elements, mechanical processing, coatings and the use of metallic glasses. The latter has limited ductility needed for implant adaptively to various surgery procedures. Furthermore, slow corroding magnesium alloys, coatings or metallic glasses have not proved to be fully dissolvable in vivo. With this in mind, we have developed a new class of biocompatible, biodegradable ductile magnesium alloys with 40% elongation at room temperature. The alloys are based on the Mg-Bi system and undergo a series of production routes, which include rapid solidification (RS) and various extrusion processes. The Mg-Bi-Si (B-BS) system exhibited a high corrosion rates in vitro and was excluded from in vivo screening. In preliminary experiments of Mg-Bi-Ca (B-BX) in rabbit femur bones, the alloy corroded rapidly without any clinically visible gas formation. Only 30% of the B-BX implant remained uncorroded after 4 weeks of implantation. After using low iron Mg for implant preparation the corrosion rate of HP-B-BX was reduced in bone leaving 70% of the implant uncorroded after 4 weeks, while the corrosion in intramuscular and subcutaneous sites were still high leaving only 40% and 10% uncorroded after 4 weeks. The foreign body reaction was very mild and enhanced bone formation could be observed in the vicinity of the corroding implant. Thus, these

  19. Umbilical cord-derived stem cells (MODULATISTTM show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-06-01

    Full Text Available Introduction: Mesenchymal stem cells (MSCs show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. and ldquo;Off the shelf and rdquo; MSC products, or so-called and ldquo;stem cell drugs and rdquo;, have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or and ldquo;drug and rdquo;, termed ModulatistTM, derived from umbilical cord mesenchymal stem cells (UCMSCs, which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs or adipose tissue-derived stem cells (ADSCs. Methods: ModulatistTM was produced from MSCs derived from whole umbilical cord (UC tissue (which includes Wharton's jelly and UC, according to GMP compliant procedures. Bone marrow- and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that ModulatistTM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. ModulatistTM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: ModulatistTM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases. [Biomed Res Ther 2016; 3(6.000: 687-696

  20. Morphological and chemical characterisation of biomimetic bone like apatite formation on alkali treated Ti6Al4V titanium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Faure, J. [INSERM-ERM 0203, Laboratoire de Microscopie Electronique, 21, rue Clement Ader, 51685 Reims, Cedex 02 (France); Balamurugan, A., E-mail: abmurugan@yahoo.co.in [INSERM-ERM 0203, Laboratoire de Microscopie Electronique, 21, rue Clement Ader, 51685 Reims, Cedex 02 (France); Department of Ceramics and Glass Engineering, University of Aveiro, CICECO, 3810-193 Aveiro (Portugal); Benhayoune, H. [INSERM-ERM 0203, Laboratoire de Microscopie Electronique, 21, rue Clement Ader, 51685 Reims, Cedex 02 (France); Torres, P. [Department of Ceramics and Glass Engineering, University of Aveiro, CICECO, 3810-193 Aveiro (Portugal); Balossier, G. [INSERM-ERM 0203, Laboratoire de Microscopie Electronique, 21, rue Clement Ader, 51685 Reims, Cedex 02 (France); Ferreira, J.M.F. [Department of Ceramics and Glass Engineering, University of Aveiro, CICECO, 3810-193 Aveiro (Portugal)

    2009-05-05

    The present study is an attempt to enhance the apatite-forming ability of titanium metal induced by the alkaline (NaOH) treatment. A cell free culture medium, acellular DMEM solution was utilised to develop bone-like apatite on alkali-treated titanium alloy surface. The main advantage of this process is the development of bone like apatite with essential trace elements on the metallic substrate by using the DMEM culture medium as a soaking medium. The formed apatite deposits were investigated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDXS). The obtained results suggest that the method utilized in this work can be successfully applied to obtain deposition of uniform coatings of crystalline hydroxyapatite on alkali treated titanium substrates.

  1. Morphological and chemical characterisation of biomimetic bone like apatite formation on alkali treated Ti6Al4V titanium alloy

    International Nuclear Information System (INIS)

    The present study is an attempt to enhance the apatite-forming ability of titanium metal induced by the alkaline (NaOH) treatment. A cell free culture medium, acellular DMEM solution was utilised to develop bone-like apatite on alkali-treated titanium alloy surface. The main advantage of this process is the development of bone like apatite with essential trace elements on the metallic substrate by using the DMEM culture medium as a soaking medium. The formed apatite deposits were investigated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDXS). The obtained results suggest that the method utilized in this work can be successfully applied to obtain deposition of uniform coatings of crystalline hydroxyapatite on alkali treated titanium substrates.

  2. Clear Zone Formation around Screws in the Early Postoperative Stages after Posterior Lumbar Fusion Using the Cortical Bone Trajectory Technique

    OpenAIRE

    Ninomiya, Koshi; Iwatsuki, Koichi; Ohnishi, Yu-ichiro; Ohkawa, Toshika; Yoshimine, Toshiki

    2015-01-01

    Study Design Retrospective study. Purpose To evaluate the initial fixation using the cortical bone trajectory (CBT) technique for posterior lumbar fusion through assessment of the clear zones around the screws and the risk factors involved. Overview of Literature Postoperative radiolucent zones (clear zones) are an indicator of poor conventional pedicle screw fixation. Methods Between January 2013 and April 2014, 19 patients (8 men and 11 women) underwent posterior lumbar interbody fusion or ...

  3. Ectopic bone formation in rapidly fabricated acellular injectable dense collagen-Bioglass hybrid scaffolds via gel aspiration-ejection

    OpenAIRE

    Miri, Amir K.; Muja, Naser; Kamranpour, Neysan O.; Lepry, William C.; Aldo R. Boccaccini; Clarke, Susan A.; Nazhat, Showan N.

    2016-01-01

    Gel aspiration-ejection (GAE) has recently been introduced as an effective technique for the rapid production of injectable dense collagen (IDC) gel scaffolds with tunable collagen fibrillar densities (CFDs) and microstructures. Herein, a GAE system was applied for the advanced production and delivery of IDC and IDC-Bioglass® (IDC-BG) hybrid gel scaffolds for potential bone tissue engineering applications. The efficacy of GAE in generating mineralizable IDC-BG gels (from an initial 75-25 coll...

  4. Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations Using sfx Mice and BXD RI Strains

    Science.gov (United States)

    Huang, Yue; Zhu, Xiaodong; Wang, Lishi; Liu, Xiaoyun; Lu, Lu; Jiao, Yan

    2014-01-01

    The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference. PMID:25133246

  5. Bone Metabolism in Anorexia Nervosa

    OpenAIRE

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in ...

  6. Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation; Role de la radiotherapie dans la prevention de l'ossification heterotopique

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, R.; Rene, N.; Souhami, L. [Department of Radiation Oncology, Montreal General Hospital, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4 (Canada); Tanzer, M. [Department of Orthopaedic Surgery, Montreal General Hospital, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4 (Canada); Evans, M. [Department of Medical Physics, Montreal General Hospital, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4 (Canada)

    2011-07-15

    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)

  7. Bone formation following lenalidomide-dexamethasone combination therapy in cases of multiple myeloma refractory to high-dose chemotherapy with bortezomib and autologous peripheral blood stem cell transplantation: report of a case and review of the literature

    Science.gov (United States)

    Sekiguchi, Yasunobu; Ichikawa, Kunimoto; Wakabayashi, Mutsumi; Sugimoto, Keiji; Tomita, Shigeki; Izumi, Hiroshi; Nakamura, Noriko; Sawada, Tomohiro; Ohta, Yasunori; Komatsu, Norio; Noguchi, Masaaki

    2015-01-01

    A 41-year-old man presented with the chief complaint of right hip pain that had persisted for 6 months. F18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showed FDG accumulation in the right pubic bone. A bone biopsy specimen from the site revealed findings suggestive of a plasma cell tumor. Bone marrow examination and serum and urine immunofixation tests showed no abnormalities. Based on these findings, the patient was diagnosed as having non-secretory multiple myeloma. FDG accumulation in the right pubic bone diminished following four cycles of weekly bortezomib and concomitant dexamethasone therapy. Tandem autologous peripheral blood stem cell transplantation was performed, followed by monthly bortezomib/dexamethasone maintenance therapy. A further FDG-PET/CT scan 9 months after the start of therapy indicated that FDG accumulation in the right pubic bone had worsened. Consequently, the therapy was switched to twice-weekly bortezomib/dexamethasone as remission re-induction therapy. New FDG uptake in the right hip bone was noted after six cycles of the therapy, and plain X-ray examination revealed osteolytic changes. The patient was then administered eight cycles of combined lenalidomide-dexamethasone therapy, which resulted in a marked decrease of the FDG accumulation in the right pubic bone and disappearance of uptake in the right hip bone. There was radiographic evidence of bone formation at these sites. This is only the second reported case in which treatment with the immunomodulatory drug lenalidomide and concomitant dexamethasone has been found to induce bone formation. PMID:26464727

  8. Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

    OpenAIRE

    Jugdaohsingh Ravin; Swaminathan Rami; Demeester Nathalie; Bevan Liisa; Clement Gail; Anderson Simon H; Calomme Mario R; Spector Tim D; Berghe Dirk; Powell Jonathan J

    2008-01-01

    Abstract Background Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial. Methods Over 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 μg cholecalciferol (Vit D3) and th...

  9. Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Jugdaohsingh Ravin

    2008-06-01

    Full Text Available Abstract Background Mounting evidence supports a physiological role for silicon (Si as orthosilicic acid (OSA, Si(OH4 in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA on markers of bone turnover and bone mineral density (BMD was investigated in a double-blind placebo-controlled trial. Methods Over 12-months, 136 women out of 184 randomized (T-score spine Results Overall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I. Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur Conclusion Combined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis. NTR 1029

  10. Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering.

    Science.gov (United States)

    Won, Jong-Eun; Yun, Ye-Rang; Jang, Jun-Hyeog; Yang, Sung-Hee; Kim, Joong-Hyun; Chrzanowski, Wojciech; Wall, Ivan B; Knowles, Jonathan C; Kim, Hae-Won

    2015-07-01

    Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration. PMID:25934278

  11. Crosstalk between cancer cells and bone microenvironment in bone metastasis

    International Nuclear Information System (INIS)

    Bone, as well as lung and liver, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers. Although the precise molecular mechanisms underlying this preference need to be elucidated, it appears that bone microenvironments possess unique biological features that enable circulating cancer cells to home, survive and proliferate, and destroy bone. In conjunction, cancers that develop bone metastases likely have the capacity to utilize these unique bone environments for colonization and bone destruction. This crosstalk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. Disruption of this interaction will allow us to design mechanism-based effective and specific therapeutic interventions for bone metastases

  12. Measurements of Enthalpy Change of Reaction of Formation, Molar Heat Capacity and Constant-Volume Combustion Energy of Solid Complex Yb(Et2dtc)3(phen)

    Institute of Scientific and Technical Information of China (English)

    Song Weiming; Hu Qilin; Chang Xuan; Chen Sanping; Xie Gang; Gao Shengli

    2006-01-01

    A ternary solid complex Yb(Et2dtc)3(phen) was obtained from the reaction of hydrous ytterbium chloride with sodium diethyldithiocarbamate (NaEt2dtc), and 1, 10-phenanthroline (o-phen·H2O) in absolute ethanol.The bonding characteristics of the complex were characterized by IR.The result shows Yb3+ bands with two sulfur atoms in the Na(Et2dtc)3 and two nitrogen atoms in the o-phen.The enthalpy change of liquid-phase reaction of formation of the complex ΔrHθm (l), was determined as being (-24.838±0.114) kJ·mol-1 at 298.15 K, by an RD-496 Ⅲ type heat conduction microcalormeter.The enthalpy change of the solid-phase reaction of formation of the complex ΔrHθm (s), was calculated as being (108.015±0.479) kJ·mol-1 on the basis of an appropriate thermochemistry cycle.The thermodynamics of liquid-phase reaction of formation of the complex was investigated by changing the temperature during the liquid-phase reaction.Fundamental parameters, the activation enthalpy, ΔHθ≠, the activation entropy, ΔSθ≠, the activation free energy, ΔGθ≠, the apparent reaction rate constant k, the apparent activation energy E, the pre-exponential constant A, and the reaction order n, were obtained by a combination of the reaction thermodynamic and kinetic equations with the data from the thermokinetic experiments.At the same time, the molar heat capacity of the complex cm, p, was determined to be (86.34±1.74) J·mol-1·K-1 by the same microcalormeter.The constant-volume combustion energy of the complex, ΔcU, was determined to be (-17954.08±8.11) kJ·mol-1 by an RBC-Ⅱ type rotating-bomb calorimeter at 298.15 K.Its standard enthalpy of combustion, ΔcHθm, and standard enthalpy of formation, ΔfHθm, were calculated to be (-17973.29±8.11) kJ·mol-1 and (-770.36±9.02) kJ·mol-1, respectively.

  13. Formation of interconnected macropores in apatitic calcium phosphate bone cement with the use of an effervescent additive.

    Science.gov (United States)

    Hesaraki, S; Moztarzadeh, F; Sharifi, D

    2007-10-01

    Calcium phosphate cements (CPCs) can be considered as good candidate for bone tissue engineering because they can be resorbed and take part in the bone remodeling process. Several efforts have been made into improve the resorption rate of the calcium phosphate cement by introducing macropores to the cement matrix. In this investigation a simple and effective method has been presented based on the addition of various amounts of an effervescent agent to the calcium phosphate cement components. The effervescent agent was a mixture of sodium hydrogen carbonate, NaHCO(3) (that was added to the powder phase), and citric acid monohydrate, C(6)H(8)O(7).H(2)O (that was dissolved in the liquid phase). The obtained macroporous samples were characterized by Fourier transform infrared spectrometer, X-ray diffraction, and scanning electron microscopy techniques at 4 h after setting and 3 days after soaking in a special simulated body fluid solution named Hank's balanced salt solution. Mercury intrusion porosimetry was also employed for characterizing the pore volume and pore size distribution in the cement structure. Results showed that the rate of conversion of staring reactant to the apatite phase and the apatite chemistry were significantly changed by using the additive in the cement components. Also both the pore volume and pore size were changed by varying both the amount of effervescent additive and the powder to liquid ratio. PMID:17380498

  14. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level

  15. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  16. Sirtuin1 (Sirt1) promotes cortical bone formation by preventing β-catenin sequestration by FoxO transcription factors in osteoblast progenitors.

    Science.gov (United States)

    Iyer, Srividhya; Han, Li; Bartell, Shoshana M; Kim, Ha-Neui; Gubrij, Igor; de Cabo, Rafael; O'Brien, Charles A; Manolagas, Stavros C; Almeida, Maria

    2014-08-29

    A decline of the levels and activity of Sirtuin1 (Sirt1), a NAD(+) class III histone deacetylase, with age contributes to the development of several diseases including type 2 diabetes, neurodegeneration, inflammation, and cancer. The anti-aging effects of Sirt1 evidently result from the deacetylation of many transcription factors and co-factors including members of the Forkhead box O (FoxO) family and β-catenin. Wnt/β-catenin is indispensable for osteoblast generation. FoxOs, on the other hand, sequester β-catenin and inhibit osteoprogenitor proliferation. Here, we have deleted Sirt1 in osteoprogenitors expressing Osterix1 (Osx1)-Cre and their descendants. Sirt1(ΔOsx1) mice had lower cortical thickness in femora and vertebrae because of reduced bone formation at the endocortical surface. In line with this, osteoprogenitor cell cultures from the Sirt1(ΔOsx1) mice exhibited lower alkaline phosphatase activity and mineralization, as well as decreased proliferation and increased apoptosis. These changes were associated with decreased Wnt/β-catenin signaling and expression of cyclin D1 and resulted from increased binding of FoxOs to β-catenin. These findings demonstrate that Sirt1-induced deacetylation of FoxOs unleashes Wnt signaling. A decline in Sirt1 activity in osteoblast progenitors with aging may, therefore, contribute to the age-related loss of bone mass. Together with evidence that Sirt1 activators increase bone mass in aged mice, our results also suggest that Sirt1 could be a therapeutic target for osteoporosis. PMID:25002589

  17. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  18. Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex

    International Nuclear Information System (INIS)

    Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient

  19. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    Science.gov (United States)

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  20. Low-temperature heat capacity and standard molar enthalpy of formation of crystalline 2-pyridinealdoxime (C6H6N2O)

    International Nuclear Information System (INIS)

    The thermodynamic properties of 2-pyridinealdoxime were investigated through the thermogravimetric (TG) analysis and differential scanning calorimetry (DSC). Low-temperature heat capacity Cp,m of 2-pyridinealdoxime (C6H6N2O; CAS 873-69-8) was measured in the temperature range from (80 to 373)K with a high precision automated adiabatic calorimeter. No phase transition or thermal anomaly was observed in this range. The thermodynamic functions [HT-H298.15] and [ST-S298.15] were calculated in the range from (80 to 375)K. The constant-volume energy and standard molar enthalpy of combustion have been determined, ΔcU(C6H6N2O,cr)=ΔcHmo (C6H6N2O, cr)=-(3297.11+/-1.53) kJ.mol-1 (based on Δn being zero in reaction of the combustion), by means of a precision oxygen-bomb combustion calorimeter at T=(298.15+/-0.001)K. The standard molar enthalpy of formation has been derived, ΔfHmo (C6H6N2O, cr)=(78.56+/-2.43) kJ.mol-1, from the standard molar enthalpy of combustion in combination with other auxiliary thermodynamic quantities through a Hess thermochemical cycle

  1. Comparison of peri-implant bone formation around injection-molded and machined surface zirconia implants in rabbit tibiae.

    Science.gov (United States)

    Kim, Hong-Kyun; Woo, Kyung Mi; Shon, Won-Jun; Ahn, Jin-Soo; Cha, Seunghee; Park, Young-Seok

    2015-01-01

    The aim of this study was to compare osseointegration and surface characteristics of zirconia implants made by the powder injection molding (PIM) technique against those made by the conventional milling procedure in rabbit tibiae. Surface characteristics of 2 types of implants were evaluated. Sixteen rabbits received 2 types of external hex implants with similar geometry, either machined zirconia implants or PIM zirconia implants, in the tibiae. Removal torque tests and histomorphometric analyses were performed. The roughness of the PIM zirconia implants was higher than that of machined zirconia implants. The PIM zirconia implants exhibited significantly higher bone-implant contact and removal torque values than the machined zirconia implants (pmold etching technique, can produce substantially rougher surfaces on zirconia implants. PMID:26235717

  2. IgE antipolymyxin B antibody formation in a T cell-depleted bone marrow transplant patient

    International Nuclear Information System (INIS)

    The production of IgE-class antibody specific for polymyxin B is documented in an 18-year-old white female acute myelocytic leukemic patient in relapse. The patient was rendered T cell--deficient by total-body x irradiation and antihuman thymocyte globulin for the purpose of bone marrow transplantation. Thereafter, symptoms of nasal congestion, rhinorrhea, and perinasal urtication produced by topical application of a polymyxin solution were noted. Reaginic activity mediated by an IgE antibody against polymyxin is documented by Prausnitz-Kuestner--type passive transfer reactions and by an indirect hemagglutination technique developed for these studies. The occurrence of type I hypersensitivity to this topical antibiotic is rare. It is speculated that pharmaceuticals normally having a low sensitizing potential might demonstrate increased reaginic immunogenicity in a spontaneously or iatrogenically T cell-depleted patient

  3. Tissue-engineered triphasic ceramic coated hydroxyapatite induced bone formation and vascularization at an extraskeletal site in a rat model

    Indian Academy of Sciences (India)

    Manitha B Nair; H K Varma; P V Mohanan; Annie John

    2011-12-01

    Tissue-engineered bone regeneration has attracted much attention because of its high clinical demand for restoration of injured tissues. In the present study, we have evaluated the capability of bare (without cells) and tissue-engineered (with osteogenic-induced rat Mesenchymal Stem Cells (MSCs)) bioactive ceramics such as hydroxyapatite (HA) and triphasic ceramic-coated hydroxyapatite (HASi) to mediate vascularisation and osteoinduction at an extraskeletal site of rat model. The viability, proliferation and osteogenic differentiation of MSCs on the scaffolds were assessed in vitro and thereby established the capability of HASi in providing a better structural habitat than HA. The vascular invasion was relatively low in bare and tissueengineered HA at 2 and 4 weeks. Interestingly, the implantation site was well vascularised with profuse ingrowth of blood capillaries in HASi groups, with preference for tissue-engineered HASi groups. Similarly, neo-osteogenesis studies were shown only by tissue-engineered HASi groups. The ingrowth of numerous osteoblast-like cells was seen around and within the pores of the material in bare HASi and tissue-engineered HASi groups (very low cellular infiltration in bare HA groups), but there was no osteoid deposition. The positive impact in forming bone in tissue-engineered HASi groups is attributable to the scaffold and to the cells, with the first choice for scaffold because both HA and HASi were engineered simultaneously with the cells from same source and same passage. Thus, highly porous interconnected porous structure and appropriate chemistry provided by HASi in combination with osteogenic-induced MSCs facilitated better vascularisation that lead to neo-osteogenesis.

  4. Combination of UV absorbance and electron donating capacity to assess degradation of micropollutants and formation of bromate during ozonation of wastewater effluents.

    Science.gov (United States)

    Chon, Kangmin; Salhi, Elisabeth; von Gunten, Urs

    2015-09-15

    In this study, the changes in UV absorbance at 254 nm (UVA254) and electron donating capacity (EDC) were investigated as surrogate indicators for assessing removal of micropollutants and bromate formation during ozonation of wastewater effluents. To measure the EDC, a novel method based on size exclusion chromatography followed by a post-column reaction was developed and calibrated against an existing electrochemical method. Low specific ozone doses led to a more efficient abatement of EDC than of UVA254. This was attributed to the abatement of phenolic moieties in the dissolved organic matter (DOM), which lose their EDC upon oxidation, but are partially transformed into quinones, which still absorb in the measured UV range. For higher specific ozone doses, the relative EDC abatement was lower than the relative UVA abatement, which can be explained by the oxidation of UV absorbing moieties (e.g. non-activated aromatic compounds), which contribute less to EDC. The abatement of the selected micropollutants (i.e., 17α-ethinylestradiol (EE2), carbamazepine (CBZ), atenolol (ATE), bezafibrate (BZF), ibuprofen (IBU), and p-chlorobenzoic acid (pCBA)) varied significantly depending on their reactivity with ozone in the examined specific ozone dose range of 0-1.45 mgO3/mgDOC. The decrease of EE2 and CBZ with high ozone reactivity was linearly proportional to the reduction of the relative residuals of UVA254 and EDC. The abatement of ATE, BZF, IBU, and pCBA with intermediate to low ozone reactivities was not significant in a first phase (UVA254/UVA254,0 = 1.00-0.70; EDC/EDC0 = 1.00-0.56) while their abatement was more efficient than the degradation of the relative residual UVA254 and much more noticeable than the degradation of the relative residual EDC in a second phase (UVA254/UVA254,0 = 0.70-0.25; EDC/EDC0 = 0.56-0.25) because the partially destroyed UV absorbing and electron donating DOM moieties become recalcitrant to ozone attack. Bromate formation was

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

    OpenAIRE

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

    2004-01-01

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

  6. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and resorpti

  7. JAW CYSTS AND GUIDED BONE REGENERATION (a late complication after enucleation

    Directory of Open Access Journals (Sweden)

    Hristina Lalabonova

    2013-10-01

    Full Text Available Maxillary jaw bone possesses a high regenerative capacity. Yet sometimes the defects enucleation of jaw cysts leaves may regenerate only partially or not at all. For this reason some researchers advise treatment of the residual cavities after cystectomy using bone regeneration stimulation methods. We report a case of an atypical complication after enucleation of a maxillary cyst manifesting itself eight years after the initial treatment. The symptoms the patient reported were at first periodic sweating on the left sides of face and head. This was followed by a piercing pain in the left palpebral fissure radiating to the middle of the palate and felt in the left cheekbone, left eye and left supraorbital ridge. The patient has a history of maxillary cysts recurring three times and of three operations she had 20, 12 and 8 years previously. The multiple recurrences of the cysts after their enucleation indicates poor regenerative capacity of the body which resulted in the formation of cicatricial tissue. It is most probably this tissue that was responsible for the disruption of the nerve conduction capacity which can account for the reported symptoms. We filled the cavity with bone graft material which boosted the bone structure regeneration. Although maxillary jaws possess high regenerative capacity we advise the use of guided bone regeneration in cases of large bone defects that usually occur after enucleation of jaw cysts.

  8. Playing with bone and fat

    DEFF Research Database (Denmark)

    Gimble, Jeffrey M.; Zvonic, Sanjin; Floyd, Z. Elisabeth;

    2006-01-01

    The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or...

  9. Development of electrospun bone-mimetic matrices for bone regenerative applications

    Science.gov (United States)

    Phipps, Matthew Christopher

    Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater

  10. Carrying Capacity

    DEFF Research Database (Denmark)

    Schroll, Henning; Andersen, Jan; Kjærgård, Bente

    2012-01-01

    carrying capacity (SCC) and assimilative carrying capacity (ACC). The act mandates that the latter two aspects must be taken into consideration in the local spatial plans. The present study aimed at developing a background for a national guideline for carrying capacity in Indonesian provinces and districts...... carrying capacity (ACC). The act mandates that the latter two aspects must be taken into consideration in the local spatial plans. The present study aimed at developing a background for a national guideline for carrying capacity in Indonesian provinces and districts/cities. Four different sectors (water...

  11. Wnt Signaling in Bone

    Science.gov (United States)

    Kubota, Takuo; Michigami, Toshimi; Ozono, Keiichi

    2010-01-01

    Wnt signaling is involved not only in embryonic development but also in maintenance of homeostasis in postnatal tissues. Multiple lines of evidence have increased understanding of the roles of Wnt signaling in bone since mutations in the LRP5 gene were identified in human bone diseases. Canonical Wnt signaling promotes mesenchymal progenitor cells to differentiate into osteoblasts. The canonical Wnt/β-catenin pathway possibly through Lrp6, a co-receptor for Wnts as well as Lrp5, in osteoblasts regulates bone resorption by increasing the OPG/RANKL ratio. However, endogenous inhibitors of Wnt signaling including sclerostin block bone formation. Regulation of sclerostin appears to be one of the mechanisms of PTH anabolic actions on bone. Since sclerostin is almost exclusively expressed in osteocytes, inhibition of sclerostin is the most promising design. Surprisingly, Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum, but not by directly promoting bone formation. Pharmacological intervention may be considered in many components of the canonical Wnt signaling pathway, although adverse effects and tumorigenicity to other tissues are important. More studies will be needed to fully understand how the Wnt signaling pathway actually influences bone metabolism and to assure the safety of new interventions. PMID:23926379

  12. [Inflammation and bone : Osteoimmunological aspects].

    Science.gov (United States)

    Frommer, K W; Neumann, E; Lange, U

    2016-06-01

    Microscopic fractures (so-called microcracks) or traumatic macrofractures require bone, as the basic scaffold of the human body, to have a high regenerative capability. In order to be able to provide this regenerative capability, bone is in a constant process of remodeling. This finely tuned homeostasis of bone formation and degradation can become disrupted, which leads to osteoporosis or other bone disorders. It has been shown that the immune system is substantially involved in the regulation of bone homeostasis and that chronic inflammation in particular can disturb this balance; therefore, this article reviews the osteoimmunological aspects contributing to osteoporosis and other diseases associated with bone degradation. PMID:27250491

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

    OpenAIRE

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

    2014-01-01

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

  14. Porous surface modified bioactive bone cement for enhanced bone bonding.

    Directory of Open Access Journals (Sweden)

    Qiang He

    Full Text Available BACKGROUND: Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth. MATERIALS AND METHODS: The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant-bone interface was also investigated by push-out tests. RESULTS: The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony

  15. PENGGUNAAN BONE GRAFT PADA PERAWATAN KERUSAKAN TULANG PERIODONTAL (Used Bone Graft for Periodontal Defect Treatment

    Directory of Open Access Journals (Sweden)

    Elly Munadziroh

    2015-07-01

    Full Text Available Generally the signs and symptoms of advances periodontal disease are periodontal pockets formation to alveolar bone defect. Bone defect treated with placement a preparation material to promote new bone formation. Tissue transplantation were developed, to recontsruct bone defect with the placement of bone graft material. This paper will discuss the used of demineralied freeze dried bone allograft (DFDBA and anorganic bone mineral combined with synthetic 15 amino acid sequence within type I collagen (PepGen P-15 the potential healing of bone defect to enhance the optimum treatment of periodontal disease.

  16. Fractionated and single-dose radiotherapy for heterotopic bone formation in patients with spinal cord injury. A phase-I/II study

    International Nuclear Information System (INIS)

    Background: Heterotopic ossification occur in about 20% of patients with spinal cord injury and may seriously compromise the rehabilitation process. Aim of the present study was to evaluate if radiotherapy administered early in the course of the disease prevents the manifestation of heterotopic ossification and if in patients whose bone formations have been resected recurrence can be avoided. Patients and Methods: 52 patients (44 males, eight females, median age 33 years) and 75 joints were irradiated between December 1989 and March 2000. 49 patients (70 joints, 65 hips, three knees, one shoulder, one elbow) were evaluable. Median follow-up was 11 months. In 58 joints radiotherapy was performed as a primary treatment in the inflammatory phase of soft tissue swelling that precedes manifestation of heterotopic ossifications. Twelve joints were treated after resection of manifest heterotopic bone, two patients had primary and postoperative irradiation in different joints. The dose was 10 Gy in single fractions of 2-2,5 Gy in 34 joints and 7.5-20 Gy in six joints. From July 1996 on, 30 joints received single-dose irradiation with 8 Gy. Results: 50/70 joints (71%) remained free from progression. This was the case for 47/65 (72%) hips, whereas in 18 hips (27%) the Brooker score increased for 1-2 grades and caused a moderate decrease of mobility in five joints. Out of the other five joints, two knees developed progression. No relevant side effects occurred. Conclusion: The present results suggest that radiotherapy is an effective local treatment option for spinal cord injured patients with heterotopic ossifications. (orig.)

  17. On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation.

    Science.gov (United States)

    Selvakumar, M; Srivastava, Priyanka; Pawar, Harpreet Singh; Francis, Nimmy K; Das, Bodhisatwa; Sathishkumar, G; Subramanian, Bhuvaneshwaran; Jaganathan, Saravana Kumar; George, Gibin; Anandhan, S; Dhara, Santanu; Nando, Golok B; Chattopadhyay, Santanu

    2016-02-17

    Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi

  18. Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

    OpenAIRE

    Shapiro, F

    2008-01-01

    Bone development occurs by two mechanisms: intramembranous bone formation and endochondral bone formation. Bone tissue forms by eventual differentiation of osteoprogenitor cells into either mesenchymal osteoblasts (MOBL), which synthesize woven bone in random orientation, or surface osteoblasts (SOBL), which synthesize bone on surfaces in a well oriented lamellar array. Bone repair uses the same formation patterns as bone development but the specific mechanism of repair is determined by the b...

  19. Space maintenance in autogenous fresh demineralized tooth blocks with platelet-rich plasma for maxillary sinus bone formation: a prospective study.

    Science.gov (United States)

    Kim, Eun-Suk; Kang, Ji-Yeon; Kim, Jae-Jin; Kim, Kyoung-Won; Lee, Eun-Young

    2016-01-01

    This prospective study evaluated the effectiveness of autogenous fresh demineralized tooth block (Auto-FDT block) with platelet-rich plasma (PRP) for maxillary sinus augmentation with simultaneous implant installation. Auto-FDT block with PRP was used in Group 1 (n = 15) and combined graft (allograft and xenograft) powder with PRP was used in Group 2 (n = 15). For up to 2 years after the final prosthesis was installed, clinical and radiographic examinations were performed to evaluate the amount of graft materials, residual alveolar height (RAH), sinus height (SH) after grafting, augmented graft height (AGH) and resorption height (RH). In ten cases, biopsies were harvested for histological and histomorphometric analyses. A total of 59 implants were placed in a severe atrophic posterior maxilla with less than 5 mm of RAH and sinus augmentation. None of the patients developed sinusitis or other complications, such as implant loss. The graft material extracted included one molar (or 2 premolars) in Group 1 and 1.8 cc in Group 2. The radiologic examination revealed the following average between-group difference SH (Group 1, 14.12 ± 1.63 mm vs Group 2, 16.51 ± 1.29 mm) and AGH (Group 1, 11.62 ± 2.22 mm vs Group 2, 13.65 ± 1.35 mm). However, sufficient SH and AGH were observed for the implants in the Auto-FDT block group. Two years after final prosthesis was installed, no between-group difference in the RH was observed (Group 1, 1.23 ± 0.73 mm vs Group 2, 1.77 ± 0.54 mm, P = 0.021). The histomorphometric analysis revealed no between-group difference in the new bone volume (Group 1, 23.13 ± 1.42 % vs Group 2, 24.18 ± 2.19 %, P = 0.548). The results showed that Auto-FDT block with PRP can be used in grafted sinuses for implants with only one extracted molar (or two premolars). Auto-FDT block with PRP promotes new bone formation that is comparable with combined grafts. Auto-FDT block with PRP is as an alternative to bone grafting

  20. Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase.

    Science.gov (United States)

    Sekiguchi, Hiroyuki; Uchida, Kentaro; Inoue, Gen; Matsushita, Osamu; Saito, Wataru; Aikawa, Jun; Tanaka, Keisuke; Fujimaki, Hisako; Miyagi, Masayuki; Takaso, Masashi

    2016-06-01

    Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016. PMID:26833780

  1. INFLUENCE OF BONE MARROW ALLOGENEIC MULTIPOTENT MESENCHYMAL STROMAL CELLS ON THE FORMATION OF ANTI-ISCHEMIC KIDNEY PROTECTION

    Directory of Open Access Journals (Sweden)

    S. S. Mescherin

    2015-01-01

    Full Text Available Аim of this work was to study the influence of intravenous injection times of bone marrow allogeneic multipotent mesenchymal stromal cells (BM MMSCs on kidney function and morphology in modeled ischemicreperfusion injury of kidney (IRIK. Materials and methods. The study was conducted on 90 male Wistar rats. On the original IRI model of a single kidney (60 min, warm ischemia 4 groups of experiments were performed: in the first group the dose of 5 × 106 of BM MMSCs was administered intravenously 14 days before IRIK modeling; in the second group, the same dose of BM MMSCs was administered 7 days before IRIK; in the third group, the same dose of BM MMSCs was administered during kidney reperfusion after IRIK modeling; the fourth group served as the control group (IRIK without BM МMSCs. The study duration was 21 days since the start of IRIK modeling. In all groups the nitrogen secretory function of kidneys was examined and the histological condition of kidneys during the entire recovery period was evaluated. Besides, blood of rats of the first and the fourth groups was examined for proand anti-inflammatory cytokine levels and phagocytosis indices using the suspension of inactivated St. aureus. The significance of differences in these two groups was evaluated by Student's test at p < 0.05. Results. It has been demonstrated that the pretreatment with BM MMSCs (1 and 2 weeks before IRIK modeling increased the anti-ischemic resistance of kidney while the administration of BM MMSCs on the day of IRIK modeling (during reperfusion enhanced kidney damage, characterized by increased mortality, elevated levels of urea and creatinine in blood and structural injury of renal tissue, as compared to other groups. The comparative analysis of the first and fourth groups shows that BM MMSCs decrease the levels of pro-inflammatory cytokines and increase the levels of anti-inflammatory cytokines, as well as enhance potential of antimicrobial protection. Conclusion

  2. Bone Biochemistry on the International Space Station

    Science.gov (United States)

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

    2016-01-01

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

  3. Multiscale imaging of bone microdamage.

    Science.gov (United States)

    Poundarik, Atharva A; Vashishth, Deepak

    2015-04-01

    Bone is a structural and hierarchical composite that exhibits remarkable ability to sustain complex mechanical loading and resist fracture. Bone quality encompasses various attributes of bone matrix from the quality of its material components (type-I collagen, mineral and non-collagenous matrix proteins) and cancellous microarchitecture, to the nature and extent of bone microdamage. Microdamage, produced during loading, manifests in multiple forms across the scales of hierarchy in bone and functions to dissipate energy and avert fracture. Microdamage formation is a key determinant of bone quality, and through a range of biological and physical mechanisms, accumulates with age and disease. Accumulated microdamage in bone decreases bone strength and increases bone's propensity to fracture. Thus, a thorough assessment of microdamage, across the hierarchical levels of bone, is crucial to better understand bone quality and bone fracture. This review article details multiple imaging modalities that have been used to study and characterize microdamage; from bulk staining techniques originally developed by Harold Frost to assess linear microcracks, to atomic force microscopy, a modality that revealed mechanistic insights into the formation diffuse damage at the ultrastructural level in bone. New automated techniques using imaging modalities, such as microcomputed tomography are also presented for a comprehensive overview. PMID:25664772

  4. A Novel Injectable Magnesium/Calcium Sulfate Hemihydrate Composite Cement for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Shanchuan Zhang

    2015-01-01

    Full Text Available Objective. A novel injectable magnesium/calcium sulfate hemihydrate (Mg/CSH composite with improved properties was reported here. Methods. Composition, setting time, injectability, compressive strength, and bioactivity in simulated body fluid (SBF of the Mg/CSH composite were evaluated. Furthermore, the cellular responses of canine bone marrow stromal cells (cBMSCs and bone formation capacity after the implantation of Mg/CSH in tibia defects of canine were investigated. Results. Mg/CSH possessed a prolonged setting time and markedly improved injectability and mechanical property p<0.05. Mg/CSH samples showed better degradability than CSH in SBF after 21 days of soaking p<0.05. Moreover, the degrees of cell attachment, proliferation, and capability of osteogenic differentiation on the Mg/CSH specimens were higher than those on CSH, without significant cytotoxicity and with the increased proliferation index, ALP activity, and expression levels of integrin β1 and Coll I in cBMSCs p<0.05. Mg/CSH enhanced the efficiency of new bone formation at the tibia defect area, including the significantly elevated bone mineral density, bone area fraction, and Coll I expression level p<0.05. Conclusions. The results implied that this new injectable bone scaffold exhibited promising prospects for bone repair and had a great potential in bone tissue engineering.

  5. Bone Cancer

    Science.gov (United States)

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

  6. Bone Cancer

    Science.gov (United States)

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

  7. Bone Diseases

    Science.gov (United States)

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

  8. Bone health in eating disorders.

    Science.gov (United States)

    Zuckerman-Levin, N; Hochberg, Z; Latzer, Y

    2014-03-01

    Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health. Low bone mineral density (BMD) with ED is caused by failure to accrue peak bone mass in adolescence and bone loss in young adulthood. Although ED patients diagnosed with bone loss may be asymptomatic, some suffer bone pains and have increased incidence of fractures. Adolescents with ED are prone to increased prevalence of stress fractures, kyphoscoliosis and height loss. The clinical picture of the various EDs involves endocrinopathies that contribute to impaired bone health. Anorexia nervosa (AN) is characterized by low bone turnover, with relatively higher osteoclastic (bone resorptive) than osteoblastic (bone formation) activity. Bone loss in AN occurs in both the trabecular and cortical bones, although the former is more vulnerable. Bone loss in AN has been shown to be influenced by malnutrition and low weight, reduced fat mass, oestrogen and androgen deficiency, glucocorticoid excess, impaired growth hormone-insulin-like growth factor 1 axis, and more. Bone loss in AN may not be completely reversible despite recovery from the illness. Treatment modalities involving hormonal therapies have limited effectiveness, whereas increased caloric intake, weight gain and resumption of menses are essential to improved BMD. PMID:24165231

  9. Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-04-01

    Full Text Available Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs. BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration.

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

    Directory of Open Access Journals (Sweden)

    Fabrizio Accardi

    2015-01-01

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

  11. Assessment of bone repair following the use of anorganic bone graft and membrane associated or not to 830-nm laser light

    Science.gov (United States)

    de Assis Limeira, Francisco, Jr.; Barbosa Pinheiro, Antônio L.; Marquez de Martinez Gerbi, Marleny E.; Pedreira Ramalho, Luciana Maria; Marzola, Clovis; Carneiro Ponzi, Elizabeth A.; Soares, Andre O.; Bandeira de Carvalho, Lívia C.; Vieira Lima, Helena Cristina; Oliveira Gonçalves, Thais; Silva Meireles, Gyselle C.; Possa, Thaise R.

    2003-06-01

    The aim of this study was to assess the effect of LLLT (λ830nm, Thera lase, DMC Equipmentos, Sao Carlos, SP, Brazil, 40mW, CW, spot size 0.60mm, 16J/cm2 per session) on the repair of bone defects on the femur of Wistar albinus rats which were grafted with anorganic bovine bone associated or not to bovine bone membrane. Five randomized groups were studied: I (Control); II (anorganic bovine bone); III (anorganic bovine bone + LLLT); IV (anorganic bovine bone + bovine bone membrane) and V (anorganic bovine bone + bovine bone membrane + LLLT). The animals were irradiated at every 48h during 15 days, the first irradiation was performed immediately after the procedure. The animals were irradiated transcutaneuosly in four points around the defect. At each point a dose of 4J/cm2 was given (f~0,60mm, 40mW) totaling 16J/cm2 per session. The animals were sacrificed 15, 21 and 30 days after surgery. The specimens were routinely processed to wax and stained with H&E and Picrosírius stains and analyzed under light microscopy. The results showed evidence of a more advanced repair on the irradiated groups when compared to non-irradiated ones. The repair of irradiated groups was characterized by both increased bone formation and amount of collagen fibers around the graft within the cavity early, considering the osteoconductive capacity of the anorganic bovine bone and the increment of the cortical repair in specimens with membrane. It is concluded that LLLT had a positive effect on the repair of bone defect submitted the implantation of graft associated or not to the use of biological membrane.

  12. Electrospun composites of PHBV/pearl powder for bone repairing

    Institute of Scientific and Technical Information of China (English)

    Jingjing Bai; Jiamu Dai; Guang Li

    2015-01-01

    Electrospun fiber has highly structural similarity with natural bone extracelluar matrix (ECM). Many researches about fabricating organic–inorganic composite materials have been carried out in order to mimic the natural composition of bone and enhance the biocompatibility of materials. In this work, pearl powder was added to the poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and the composite nanofiber scaffold was prepared by electrospinning. Mineralization ability of the composite scaffolds can be evaluated by analyzing hydroxyapatite (HA) formation on the surface of nanofiber scaffolds. The obtained composite nanofiber scaffolds showed an enhanced mineralization capacity due to incorporation of pearl powder. The HA formed amount of the composite scaffolds was raised as the increase of pearl powder in composite scaffolds. Therefore, the prepared PHBV/pearl composite nanofiber scaffolds would be a promising candidate as an osteoconductive composite material for bone repairing.

  13. Electrospun composites of PHBV/pearl powder for bone repairing

    Directory of Open Access Journals (Sweden)

    Jingjing Bai

    2015-08-01

    Full Text Available Electrospun fiber has highly structural similarity with natural bone extracelluar matrix (ECM. Many researches about fabricating organic–inorganic composite materials have been carried out in order to mimic the natural composition of bone and enhance the biocompatibility of materials. In this work, pearl powder was added to the poly (3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV and the composite nanofiber scaffold was prepared by electrospinning. Mineralization ability of the composite scaffolds can be evaluated by analyzing hydroxyapatite (HA formation on the surface of nanofiber scaffolds. The obtained composite nanofiber scaffolds showed an enhanced mineralization capacity due to incorporation of pearl powder. The HA formed amount of the composite scaffolds was raised as the increase of pearl powder in composite scaffolds. Therefore, the prepared PHBV/pearl composite nanofiber scaffolds would be a promising candidate as an osteoconductive composite material for bone repairing.

  14. Functionalisation of PLLA nanofiber scaffolds using a possible cooperative effect between collagen type I and BMP-2: impact on colonization and bone formation in vivo

    OpenAIRE

    Schofer, Markus D.; Tünnermann, Lisa; Kaiser, Hendric; Roessler, Philip P; Theisen, Christina; Heverhagen, Johannes T.; Hering, Jacqueline; Voelker, Maximilian; Agarwal, Seema; Efe, Turgay; Fuchs-Winkelmann, Susanne; Paletta, Jürgen R. J.

    2012-01-01

    The reconstruction of large bone defects after injury or tumor resection often requires the use of bone substitution. Artificial scaffolds based on synthetic biomaterials can overcome disadvantages of autologous bone grafts, like limited availability and donor side morbidity. Among them, scaffolds based on nanofibers offer great advantages. They mimic the extracellular matrix, can be used as a carrier for growth factors and allow the differentiation of human mesenchymal stem cells. Differenti...

  15. Formation of acellular cementum-like layers, with and without extrinsic fiber insertion, along inert bone surfaces of aging c-Src gene knockout mice.

    Science.gov (United States)

    Baba, Otto; Miyata, Atsushi; Abe, Tatsuhiko; Shibata, Shunichi; Nakano, Yukiko; Terashima, Tatsuo; Oda, Tsuyoshi; Kudo, Akira; Takano, Yoshiro

    2006-12-01

    To investigate the long-term effects of c-src deficiency on skeletal and dental tissues, we examined the lower jaws and long bones of c-src gene knockout (c-src KO) mice by histological and histochemical methods. Numerous multinucleated osteoclasts were distributed throughout the mandible in 5-wk-old c-src KO mice, but by 14 wk they had almost completely disappeared from the alveolar bone, leaving tartrate-resistant acid phosphatase (TRAP)-positive layers along the bone surface. Deposition of osteopontin-positive mineralized tissue, reminiscent of acellular afibrillar cementum (AAC), was confirmed along the TRAP-positive bone surface at 14 wk. The layer progressively thickened up to 21 months. A comparable mineralized layer was noted along the trabeculae of long bones as thickened cement lines. In the periostin-rich areas of jaw bones, but not in the long bones, portions of AAC-like mineralized layers were often replaced with and/or covered by acellular extrinsic fiber cementum (AEFC)-like tissue. These data suggest that the deposition of AAC-like mineralized tissue is a general phenomenon that may occur along inert or slowly remodeling bone surfaces under conditions characterized by reduced bone-resorbing activity, whereas the induction of AEFC-like tissue seems to be associated with the expression of certain molecules that are particularly abundant in the microenvironment of the periodontal ligament. PMID:17184236

  16. Reducing the Risk of Bone Fracture: A Review of the Research for Adults with Low Bone Density

    Science.gov (United States)

    ... of the Research for Adults With Low Bone Density Formats View PDF (PDF) 1.0 MB Download ... cfm . Understanding Your Condition What is low bone density? Low bone density is a condition where the ...

  17. Diabetes-induced fibrotic matrix inhibits intramembranous bone healing

    OpenAIRE

    Khosravi, Roozbeh; Trackman, Philip C.

    2014-01-01

    Diabetes diminishes bone healing and ossification. Reduced bone formation in intramembranous ossification is known, yet the mechanism(s) behind impaired intramembranous bone healing are unclear. Here we report the formation of a fibrotic matrix during healing of intramembranous calvarial bone defects that appears to exclude new bone growth. Our histological analyses of 7-day and 14-day calvaria bone healing tissue in chemically-induced diabetic mice and non-diabetic mice showed the accumulati...

  18. Low-level vibrations retain bone marrow's osteogenic potential and augment recovery of trabecular bone during reambulation.

    Directory of Open Access Journals (Sweden)

    Engin Ozcivici

    Full Text Available Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising the regenerative capacity of the stem cell pool and impeding the rapid and full recovery of bone morphology. Here, it was tested whether brief daily exposure to high-frequency, low-magnitude vibrations can preserve the marrow environment during disuse and enhance the initiation of tissue recovery upon reambulation. Male C57BL/6J mice were subjected to hindlimb unloading (HU, n = 24, HU interrupted by weight-bearing for 15 min/d (HU+SHAM, n = 24, HU interrupted by low-level whole body vibrations (0.2 g, 90 Hz for 15 min/d (HU+VIB, n = 24, or served as age-matched controls (AC, n = 24. Following 3 w of disuse, half of the mice in each group were released for 3 w of reambulation (RA, while the others were sacrificed. RA+VIB mice continued to receive vibrations for 15 min/d while RA+SHAM continued to receive sham loading. After disuse, HU+VIB mice had a 30% greater osteogenic marrow stromal cell population, 30% smaller osteoclast surface, 76% greater osteoblast surface but similar trabecular bone volume fraction compared to HU. After 3 w of reambulation, trabecular bone of RA+VIB mice had a 30% greater bone volume fraction, 51% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation rates, and a 235% greater ratio of bone lining osteoblasts to marrow adipocytes than RA mice. A subsequent experiment indicated that receiving the mechanical intervention only during disuse, rather than only during reambulation, was more effective in altering trabecular morphology. These data indicate that the osteogenic potential of bone marrow cells is retained by low-magnitude vibrations during disuse, an attribute which may have contributed to an enhanced recovery of bone morphology during reambulation.

  19. Myeloma bone disease: Pathophysiology and management

    OpenAIRE

    Silbermann, Rebecca; Roodman, G. David

    2013-01-01

    Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the ...

  20. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

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

    OpenAIRE

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

    2013-01-01

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

  2. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  3. [Bone metabolic markers and diagnosis of abnormal bone and calcium metabolism].

    Science.gov (United States)

    Fukunaga, M; Sone, T

    2001-07-01

    Bone metabolic markers increase in blood or urine, when bone formation or bone resorption accelerates. Reference values of bone metabolic markers are determined in male or female, and in pre- or post-menopause, respectively. Values of bone metabolic markers in most patients with primary osteoporosis were distributed within a reference value, mean+/-1.96 SD. When measured values exceeded a reference values, we should survey a possibility of abnormal calcium or bone metabolism such as primary hyperparathyroidism, renal osteodystrophy, hyperthyroidism and Paget's disease of bone or bone metastasis associated with malignant tumor. PMID:15775589

  4. ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

    Directory of Open Access Journals (Sweden)

    C. Rentsch

    2014-01-01

    Full Text Available Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100% and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant.

  5. ECM inspired coating of embroidered 3D scaffolds enhances calvaria bone regeneration.

    Science.gov (United States)

    Rentsch, C; Rentsch, B; Heinemann, S; Bernhardt, R; Bischoff, B; Förster, Y; Scharnweber, D; Rammelt, S

    2014-01-01

    Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

  6. Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

    Science.gov (United States)

    Lee, Dong Joon; Park, Yonsil; Hu, Wei-Shou; Ko, Ching-Chang

    2016-01-01

    Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluated in vivo by the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formation in vitro and induced new bone formation by the effect of rMAPC aggregates in vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration. PMID:27239552

  7. The response of bone to unloading

    Science.gov (United States)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  8. Low Bone Density

    Science.gov (United States)

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

  9. The research progress on the functions of microRNA in bone formation%microRNA对骨形成的调控作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘梦珺; 刘璐; 李荣荣; 张琰; 刘东旭

    2016-01-01

    MicroRNAs ( miRNAs) are a class of noncoding single-stranded RNA molecules composed of approximately 20-24 nucleo-tides. These small miRNAs can negatively regulate gene expression through 3' untranslated region (UTR) of mRNAs bound to the tar-get genes. Bone organogenesis is a complex process, which involves the differentiation and crosslinking of multiple cell types for the formation and remodeling of the skeleton. The existing evidence indicates that miRNAs control multiple layers of gene regulation for bone development and postnatal functions. Currently, inhibition of mRNA translation by miRNAs has been regarded as an important regulator for bone development and homeostasis. This review focused on the current knowledge of miRNAs and their involvement in the regulation of bone formation and bone resorption.%microRNAs是一类由20~24个核苷酸组成的非编码单链RNA,通过结合于靶基因的mRNA的3’ UTR,负向调控基因表达。骨形成是一个复杂的过程,其中涉及了多种细胞的分化和交联来完成骨的形成和重塑。研究证明,miRNA调控骨发生发展和出生后的功能的多个层面。目前,miRNA已被认为是调控骨发育与维持骨稳态的重要调节因子。该文主要针对目前关于miRNA调控骨形成和骨吸收的研究及其进展作一综述。

  10. Temporal response of bone to unloading

    International Nuclear Information System (INIS)

    A model of weightlessness in which the hindlimbs of rats are elevated by their tails at a 40 degrees angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with 45Ca and [3H]proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more 45Ca and [3H]proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that this model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading

  11. Temporal response of bone to unloading

    Energy Technology Data Exchange (ETDEWEB)

    Globus, R.K.; Bikle, D.D.; Morey-Holton, E.

    1986-02-01

    A model of weightlessness in which the hindlimbs of rats are elevated by their tails at a 40 degrees angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with /sup 45/Ca and (/sup 3/H)proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more /sup 45/Ca and (/sup 3/H)proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that this model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading.

  12. Tailored Surface Treatment of 3D Printed Porous Ti6Al4V by Microarc Oxidation for Enhanced Osseointegration via Optimized Bone In-Growth Patterns and Interlocked Bone/Implant Interface.

    Science.gov (United States)

    Xiu, Peng; Jia, Zhaojun; Lv, Jia; Yin, Chuan; Cheng, Yan; Zhang, Ke; Song, Chunli; Leng, Huijie; Zheng, Yufeng; Cai, Hong; Liu, Zhongjun

    2016-07-20

    3D printed porous titanium (Ti) holds enormous potential for load-bearing orthopedic applications. Although the 3D printing technique has good control over the macro-sturctures of porous Ti, the surface properties that affect tissue response are beyond its control, adding the need for tailored surface treatment to improve its osseointegration capacity. Here, the one step microarc oxidation (MAO) process was applied to a 3D printed porous Ti6Al4V (Ti64) scaffold to endow the scaffold with a homogeneous layer of microporous TiO2 and significant amounts of amorphous calcium-phosphate. Following the treatment, the porous Ti64 scaffolds exhibited a drastically improved apatite forming ability, cyto-compatibility, and alkaline phosphatase activity. In vivo test in a rabbit model showed that the bone in-growth at the untreated scaffold was in a pattern of distance osteogenesis by which bone formed only at the periphery of the scaffold. In contrast, the bone in-growth at the MAO-treated scaffold exhibited a pattern of contact osteogenesis by which bone formed in situ on the entire surface of the scaffold. This pattern of bone in-growth significantly increased bone formation both in and around the scaffold possibly through enhancement of bone formation and disruption of bone remodeling. Moreover, the implant surface of the MAO-treated scaffold interlocked with the bone tissues through the fabricated microporous topographies to generate a stronger bone/implant interface. The increased osteoinetegration strength was further proven by a push out test. MAO exhibits a high efficiency in the enhancement of osteointegration of porous Ti64 via optimizing the patterns of bone in-growth and bone/implant interlocking. Therefore, post-treatment of 3D printed porous Ti64 with MAO technology might open up several possibilities for the development of bioactive customized implants in orthopedic applications. PMID:27341499

  13. Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice

    OpenAIRE

    Kim, Misung; Na, Woori; Sohn, Cheongmin

    2013-01-01

    Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1...

  14. Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering

    OpenAIRE

    Won, J. E.; Yun, Y. R.; Jang, J. H.; S. H. Yang; Kim, J. H.; W. Chrzanowski; Wall, I. B.; Knowles, J. C.; Kim, H. W.

    2015-01-01

    Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctio...