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Sample records for bone development

  1. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram...... lambs were randomly assigned to two weight-matched groups at birth. During the first 14 days of life AKG was administered orally to the experimental group (n=12) at the dosage of 0.1 g/kg body weight per day, while the control group (n=11) received an equal dose of the vehicle. Lambs were slaughtered...... has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development...

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Bmp2 and Bmp4 accelerate alveolar bone development.

    Science.gov (United States)

    Ou, Mingming; Zhao, Yibing; Zhang, Fangming; Huang, Xiaofeng

    2015-06-01

    Alveolar bone remodeling is a continuous process that takes place during development and in response to various physiological and pathological stimuli. However, detailed knowledge regarding the underlying mechanisms involved in alveolar bone development is still lacking. This study aims at improving our understanding of alveolar bone formation and the role of bone morphogenetic proteins (Bmps) in this process. Mice at embryonic (E) day 13.5 to postnatal (PN) day 15.5 were selected to observe the process of alveolar bone development. Alveolar bone development was found to be morphologically observable at E14.5. Molar teeth isolated from mice at PN7.5 were pretreated with Bmp2, Bmp4, Noggin, or BSA, and grafted subcutaneously into mice. The subcutaneously implanted tooth germs formed alveolar bone indicating the role of the dental follicle in alveolar bone development. Alveolar bone formation was increased after pretreatment with Bmp2 and Bmp4, but not with Noggin. Gene expression levels in dental follicle cells from murine molars were also determined by real-time RT-PCR. The expression levels of Runx2, Bsp, and Ocn were significantly higher in dental follicle cells cultured with Bmp2 or Bmp4, and significantly lower in those cultured with Noggin when compared with that of the BSA controls. Our results suggest that the dental follicle participates in alveolar bone formation and Bmp2/4 appears to accelerate alveolar bone development.

  4. Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development

    Directory of Open Access Journals (Sweden)

    Agata Witkowska

    2014-10-01

    Full Text Available The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8–12 months and life expectancy is ∼5–6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23 that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0–1 month, 1–3 months, 3–6 months, 6 months–1 year and 1–4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point

  5. Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development.

    Science.gov (United States)

    Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J; Rutland, Catrin S

    2014-01-01

    The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8-12 months and life expectancy is ∼5-6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0-1 month, 1-3 months, 3-6 months, 6 months-1 year and 1-4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have

  6. Bone resorption: an actor of dental and periodontal development?

    Science.gov (United States)

    Gama, Andrea; Navet, Benjamin; Vargas, Jorge William; Castaneda, Beatriz; Lézot, Frédéric

    2015-01-01

    Dental and periodontal tissue development is a complex process involving various cell-types. A finely orchestrated network of communications between these cells is implicated. During early development, communications between cells from the oral epithelium and the underlying mesenchyme govern the dental morphogenesis with successive bud, cap and bell stages. Later, interactions between epithelial and mesenchymal cells occur during dental root elongation. Root elongation and tooth eruption require resorption of surrounding alveolar bone to occur. For years, it was postulated that signaling molecules secreted by dental and periodontal cells control bone resorbing osteoclast precursor recruitment and differentiation. Reverse signaling originating from bone cells (osteoclasts and osteoblasts) toward dental cells was not suspected. Dental defects reported in osteopetrosis were associated with mechanical stress secondary to defective bone resorption. In the last decade, consequences of bone resorption over-activation on dental and periodontal tissue formation have been analyzed with transgenic animals (RANK (Tg) and Opg (-∕-) mice). Results suggest the existence of signals originating from osteoclasts toward dental and periodontal cells. Meanwhile, experiments consisting in transitory inhibition of bone resorption during root elongation, achieved with bone resorption inhibitors having different mechanisms of action (bisphosphonates and RANKL blocking antibodies), have evidenced dental and periodontal defects that support the presence of signals originating bone cells toward dental cells. The aim of the present manuscript is to present the data we have collected in the last years that support the hypothesis of a role of bone resorption in dental and periodontal development.

  7. Development and clinical trial of a novel bioactive bone cement

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Strontium(Sr)and related compounds have become more attractive in the prevention and treatment of osteoporosis.Previously,we developed a novel bioactive bone cement which is mainly composed of strontium-containing hydroxyapatite(Sr-HA)filler and bisphenol A diglycidylether dimethacrylate(Bis-GMA)resin.This bone cement is superior to conventional polymethylmethacrylate (PMMA)bone cement in bioactivity,biocompatibility,and osseointegration.It also has shown sufficient mechanical strength properties for its use in percutaneous vertebroplasty(PVP)and total hip replacement(THR).In this paper,we review the in vitro,in vivo and clinical evidence for the effectiveness of this bioactive bone cement.

  8. 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

  9. A newly developed snack effective for enhancing bone volume

    Directory of Open Access Journals (Sweden)

    Hayashi Hidetaka

    2009-07-01

    Full Text Available Abstract Background The incidence of primary osteoporosis is higher in Japan than in USA and European countries. Recently, the importance of preventive medicine has been gradually recognized in the field of orthopaedic surgery with a concept that peak bone mass should be increased in childhood as much as possible for the prevention of osteoporosis. Under such background, we have developed a new bean snack with an aim to improve bone volume loss. In this study, we examined the effects of a newly developed snack on bone volume and density in osteoporosis model mice. Methods Orchiectomy (ORX and ovariectomy (OVX were performed for C57BL/6J mice of twelve-week-old (Jackson Laboratory, Bar Harbar, ME, USA were used in this experiment. We prepared and given three types of powder diet e.g.: normal calcium diet (NCD, Ca: 0.9%, Clea Japan Co., Tokyo, Japan, low calcium diet (LCD, Ca: 0.63%, Clea Japan Co., and special diet (SCD, Ca: 0.9%. Eighteen weeks after surgery, all the animals were sacrified and prepared for histomorphometric analysis to quantify bone density and bone mineral content. Results As a result of histomorphometric examination, SCD was revealed to enhance bone volume irrespective of age and sex. The bone density was increased significantly in osteoporosis model mice fed the newly developmental snack as compared with the control mice. The bone mineral content was also enhanced significantly. These phenomena were revealed in both sexes. Conclusion It is shown that the newly developed bean snack is highly effective for the improvement of bone volume loss irrespective of sex. We demonstrated that newly developmental snack supplements may be a useful preventive measure for Japanese whose bone mineral density values are less than the ideal condition.

  10. Osteoma of the Pharynx That Developed from the Hyoid Bone

    Directory of Open Access Journals (Sweden)

    Akira Hagiwara

    2014-01-01

    Full Text Available This paper reports on apparently the first case of a pharyngeal osteoma that developed from the hyoid bone. An 84-year-old man’s, presenting symptom was a slight throat pain. Endoscopic examination revealed a huge mass occluding the pharyngeal space. CT scan of the neck showed a large osseous mass adjacent to the hyoid bone. Transoral resection with tracheostomy was performed. Histopathologically, the tumor consisted of mature lamellar bone without a fibrous component. For two years postoperatively, the patient has been free from throat symptoms and signs of recurrence. Osteomas are benign, slow-growing tumors. They rarely develop symptoms or cause functional disturbance. We performed total resection to avoid further functional disturbance as the osteoma was huge. To the best of our knowledge, this is the first report on an osteoma that occupied the pharyngeal space and developed from the hyoid bone.

  11. Col11a1 Regulates Bone Microarchitecture during Embryonic Development

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    Anthony Hafez

    2015-12-01

    Full Text Available Collagen XI alpha 1 (Col11a1 is an extracellular matrix molecule required for embryonic development with a role in both nucleating the formation of fibrils and regulating the diameter of heterotypic fibrils during collagen fibrillar assembly. Although found in many different tissues throughout the vertebrate body, Col11a1 plays an essential role in endochondral ossification. To further understand the function of Col11a1 in the process of bone formation, we compared skeletal mineralization in wild-type (WT mice and Col11a1-deficient mice using X-ray microtomography (micro-CT and histology. Changes in trabecular bone microstructure were observed and are presented here. Additionally, changes to the periosteal bone collar of developing long bones were observed and resulted in an increase in thickness in the case of Col11a1-deficient mice compared to WT littermates. Vertebral bodies were incompletely formed in the absence of Col11a1. The data demonstrate that Col11a1 depletion results in alteration to newly-formed bone and is consistent with a role for Col11a1 in mineralization. These findings indicate that expression of Col11a1 in the growth plate and perichondrium is essential for trabecular bone and bone collar formation during endochondral ossification. The observed changes to mineralized tissues further define the function of Col11a1.

  12. Development of a piezoelectric bone substitute material

    CERN Document Server

    Al-Bader, Y A

    2000-01-01

    The thesis deals with the preparation and testing of ceramic compositions to be used as bone substitute. The proposed composition consisted of calcium enriched calcium phosphate, kaolin and barium titanate in different ratios. The homogeneous powder mixture was dry pressed at different pressures and fired at temperatures up to 1350 degC for different soaking times. The physical properties of the fired compacts that were tested are bulk density and porosity. These were determined as function of pressing pressure, firing temperature and soaking time for different compositions. The mechanical properties investigated were the ultimate compressive strength and Young's modulus, which were determined for different compositions and forming pressures. The electrical properties investigated were D.C. characteristics (resistivity) and A.C. characteristics (A.C. resistivity, dielectric constant, dielectric loss and loss tangent). The piezoelectric behaviour of the fired compacts was investigated and the piezoelectric coe...

  13. Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

    Directory of Open Access Journals (Sweden)

    SA Lanham

    2011-11-01

    Full Text Available It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother’s nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspring is determined during gestation.

  14. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

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

  15. Late sarcoma development after curettage and bone grafting of benign bone tumors

    Energy Technology Data Exchange (ETDEWEB)

    Picci, Piero, E-mail: piero.picci@ior.it [Bone Tumor Center, Istituto Ortopedico Rizzoli, Bologna (Italy); Sieberova, Gabriela [Dept. of Pathology, National Cancer Institute, Bratislava (Slovakia); Alberghini, Marco; Balladelli, Alba; Vanel, Daniel [Bone Tumor Center, Istituto Ortopedico Rizzoli, Bologna (Italy); Hogendoorn, Pancras C.W. [Dept. of Pathology, Leiden University Medical Center, Leiden (Netherlands); Mercuri, Mario [Bone Tumor Center, Istituto Ortopedico Rizzoli, Bologna (Italy)

    2011-01-15

    Background and aim: Rarely sarcomas develop in previous benign lesions, after a long term disease free interval. We report the experience on these rare cases observed at a single Institution. Patients and methods: 12 cases curetted and grafted, without radiotherapy developed sarcomas, between 1970 and 2005, 6.5-28 years from curettage (median 18, average 19). Age ranged from 13 to 55 years (median 30, average 32) at first diagnosis; tumors were located in the extremities (9 GCT, benign fibrous histiocytoma, ABC, and solitary bone cyst). Radiographic and clinic documentation, for the benign and malignant lesions, were available. Histology was available for 7 benign and all malignant lesions. Results: To fill cavities, autogenous bone was used in 4 cases, allograft in 2, allograft and tricalcium-phosphate/hydroxyapatite in 1, autogenous/allograft in 1, heterogenous in 1. For 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 osteosarcoma, 3 malignant fibrous histiocytoma, and 1 fibrosarcoma. Conclusions: Recurrences with progression from benign tumors are possible, but the very long intervals here reported suggest a different cancerogenesis for these sarcomas. This condition is extremely rare accounting for only 0.26% of all malignant bone sarcomas treated in the years 1970-2005 and represents only 8.76% of all secondary bone sarcomas treated in the same years. This incidence is the same as that of sarcomas arising on fibrous dysplasia, and is lower than those arising on bone infarcts or on Paget's disease. This possible event must be considered during follow-up of benign lesions.

  16. New developments in bone-conduction hearing implants: a review

    Directory of Open Access Journals (Sweden)

    Reinfeldt S

    2015-01-01

    Full Text Available Sabine Reinfeldt,1 Bo Håkansson,1 Hamidreza Taghavi,1 Måns Eeg-Olofsson21Department of Signals and Systems, Chalmers University of Technology, Gothenburg, Sweden; 2Department of Otorhinolaryngology, Head and Neck Surgery, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenAbstract: The different kinds of bone-conduction devices (BCDs available for hearing rehabilitation are growing. In this paper, all BCDs currently available or in clinical trials will be described in categories according to their principles. BCDs that vibrate the bone via the skin are referred to as skin-drive devices, and are divided into conventional devices, which are attached with softbands, for example, and passive transcutaneous devices, which have implanted magnets. BCDs that directly stimulate the bone are referred to as direct-drive devices, and are further divided into percutaneous and active transcutaneous devices; the latter have implanted transducers directly stimulating the bone under intact skin. The percutaneous direct-drive device is known as a bone-anchored hearing aid, which is the BCD that has the largest part of the market today. Because of some issues associated with the percutaneous implant, and to some extent because of esthetics, more transcutaneous solutions with intact skin are being developed today, both in the skin-drive and in the direct-drive category. Challenges in developing transcutaneous BCDs are mostly to do with power, attachment, invasiveness, and magnetic resonance imaging compatibility. In the future, the authors assume that the existing percutaneous direct-drive BCD will be retained as an important rehabilitation alternative, while the transcutaneous solutions will increase their part of the market, especially for patients with bone-conduction thresholds better than 35 dB HL (hearing level. Furthermore, the active transcutaneous direct-drive BCDs appear to be the most promising systems

  17. Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

    OpenAIRE

    Bassett, J.H. Duncan; Williams, Graham R

    2016-01-01

    The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing...

  18. Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

    Directory of Open Access Journals (Sweden)

    F Shapiro

    2008-04-01

    Full Text Available 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 biomechanical environment provided. Bone synthesis and maintenance are highly dependent on the blood supply of bone and on cell-cell communication via the lacunar-canalicular system. Recent investigations highlight the molecular cascades leading to cell differentiation, the components of the structural proteins such as the various collagens, and tissue vascularization. The patterning of bone matrix from an initial woven to an eventual lamellar orientation is essential for bone to develop its maximum strength. This review demonstrates the repetitive nature of woven to lamellar bone formation as mediated by MOBLs and SOBLs in both normal vertebrate bones and bone repair. Repair, using endochondral, primary, direct and distraction osteogenesis mechanisms, is reviewed along with the associated molecular, vascular, and biophysical features.

  19. Risk factors for developing mineral bone disease in phenylketonuric patients.

    Science.gov (United States)

    Mirás, Alicia; Bóveda, M Dolores; Leis, María R; Mera, Antonio; Aldámiz-Echevarría, Luís; Fernández-Lorenzo, José R; Fraga, José M; Couce, María L

    2013-03-01

    There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33 ± 8.95 g vs 21.25 ± 20.85 g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1 years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass.

  20. Influence of Exercise and Training on Critical Stages of Bone Growth and Development.

    Science.gov (United States)

    Klentrou, Panagiota

    2016-05-01

    Although osteoporosis is considered a geriatric disease, factors affecting bone strength are most influential during child growth and development. This article reviews what is known and still unclear in terms of bone growth, development and adaptation relative to physical activity before and during puberty. Bone is responsive to certain exercise protocols early in puberty and less so in postpubertal years, where bone strength, rather than bone mass, being the outcome of interest. Mechanical loading and high impact exercise promote bone strength. Intense training before and during puberty, however, may negatively affect bone development. Future research should focus on increasing our mechanistic understanding of the manner by which diverse physical stressors alter the integrity of bone. Longitudinal studies that examine the extent to which muscle and bone are comodulated by growth in children are also recommended.

  1. Development of a clinically applicable tool for bone density assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Y. [Katholieke Universiteit Leuven, Oral Imaging Center, Faculty of Medicine, Leuven (Belgium); St John' s Hospital, Department of Oral and Maxillofacial Surgery, Genk (Belgium); Dobbelaer, B. de; Suetens, P. [Katholieke Universiteit Leuven, Medical Image Computing (PSI), Faculty of Engineering, Leuven (Belgium); Nackaerts, O.; Yan, B.; Jacobs, R. [Katholieke Universiteit Leuven, Oral Imaging Center, Faculty of Medicine, Leuven (Belgium); Loubele, M. [Katholieke Universiteit Leuven, Oral Imaging Center, Faculty of Medicine, Leuven (Belgium); Katholieke Universiteit Leuven, Medical Image Computing (PSI), Faculty of Engineering, Leuven (Belgium); Politis, C.; Vrielinck, L. [St John' s Hospital, Department of Oral and Maxillofacial Surgery, Genk (Belgium); Schepers, S. [St John' s Hospital, Department of Oral and Maxillofacial Surgery, Genk (Belgium); University of Gent, Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Gent (Belgium); Lambrichts, I. [University of Hasselt, Department of Morphology, Diepenbeek (Belgium); Horner, K.; Devlin, H. [University of Manchester, School of Dentistry, Manchester (United Kingdom)

    2009-03-15

    To assess the accuracy and reliability of new software for radiodensitometric evaluations. A densitometric tool developed by MevisLab {sup registered} was used in conjunction with intraoral radiographs of the premolar region in both in vivo and laboratory settings. An aluminum step wedge was utilized for comparison of grey values. After computer-aided segmentation, the interproximal bone between the premolars was assessed in order to determine the mean grey value intensity of this region and convert it to a thickness in aluminum. Evaluation of the tool was determined using bone mineral density (BMD) values derived from decalcified human bone specimens as a reference standard. In vivo BMD data was collected from 35 patients as determined with dual X-ray absorptiometry (DXA). The intra and interobserver reliability of this method was assessed by Bland and Altman Plots to determine the precision of this tool. In the laboratory study, the threshold value for detection of bone loss was 6.5%. The densitometric data (mm Al eq.) was highly correlated with the jaw bone BMD, as determined using dual X-ray absorptiometry (r=0.96). For the in vivo study, the correlations between the mm Al equivalent of the average upper and lower jaw with the lumbar spine BMD, total hip BMD and femoral neck BMD were 0.489, 0.537 and 0.467, respectively (P<0.05). For the intraobserver reliability, a Bland and Altman plot showed that the mean difference {+-}1.96 SD were within {+-}0.15 mm Al eq. with the mean difference value small than 0.003 mm Al eq. For the interobserver reliability, the mean difference {+-}1.96 SD were within {+-}0.11 mm Al eq. with the mean difference of 0.008 mm Al eq. A densitometric software tool has been developed, that is reliable for bone density assessment. It now requires further investigation to evaluate its accuracy and clinical applicability in large scale studies. (orig.)

  2. The impact of bone development on final carcass weight

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.;

    2006-01-01

    Proper development and function of the skeleton is crucial for the optimal growth of an organism, with rapid growth rates often resulting in skeletal disorders in farm animals. Yet, despite clear benefits for breed selection and animal welfare (HARRISON et al., 2004), the impact of bone development...... on final livestock characteristics remains largely undetermined. Male Shropshire lambs, sired by a ram with a high genetic potential for daily live weight gain (n=11), or a ram with a high genetic potential for both daily gain and lean content (n=12), were slaughtered at a mean age of 146 days. The femur...

  3. Development of bioactive materials using reticulated ceramics for bone substitute

    Science.gov (United States)

    Jiang, Gengwei

    For hard tissue prosthetics, it is necessary to seek novel synthesis routes by which a real structural bone can be simulated in terms of bioactivity, porosity, and mechanical behavior. The work presented here deals with the development of such a component by a novel synthesis route for bone implantation. To enhance the mechanical properties, an industrial alumina has been selected as the substrate. Alumina is not only bio inert but also mechanically strong which makes it an ideal substrate for bone substitute. The high porosity is achieved via a sponge technique by which both pore size and density can be changed easily. The bioactivity is induced by coating a highly bioactive HA film onto the inner pore surfaces of the reticulated alumina. Based on this concept, the research has focused on the coating of HA onto inner pore surfaces of the reticulated alumina via several effective methods that are developed in our laboratory. No previous studies have so far been reported on coating inner surfaces of small-diameter pores ranging from 0.1--1.0 mm. The key materials processing issues dealt with in this work include precursor chemistry, coating procedures, synthesis of coated component, interface structure study, film adhesion strength testing, and mechanical properties of the component. This novel approach has shown great promise in synthesizing bone substitutes. To determine the applicability of the coated component in hard tissue prosthetics, a bioactivity study has been carried out. By immersing the synthetic HA into simulated body fluid (SBF), the bioresponse has been measured for a variety of samples with different processing conditions. Fundamental aspects of this study are centered on the effects of structural characteristics of HA on the bioactivity. Based on extensive IR and XRD experimental data, it has been found that the bioactivity of HA is sensitively controlled by the structural crystallinity of the HA and its specific surface area. Furthermore, based on

  4. Development and mechanical characterization of porous titanium bone substitutes.

    Science.gov (United States)

    Barbas, A; Bonnet, A-S; Lipinski, P; Pesci, R; Dubois, G

    2012-05-01

    Commercially Pure Porous Titanium (CPPTi) can be used for surgical implants to avoid the stress shielding effect due to the mismatch between the mechanical properties of titanium and bone. Most researchers in this area deal with randomly distributed pores or simple architectures in titanium alloys. The control of porosity, pore size and distribution is necessary to obtain implants with mechanical properties close to those of bone and to ensure their osseointegration. The aim of the present work was therefore to develop and characterize such a specific porous structure. First of all, the properties of titanium made by Selective Laser Melting (SLM) were characterized through experimental testing on bulk specimens. An elementary pattern of the porous structure was then designed to mimic the orthotropic properties of the human bone following several mechanical and geometrical criteria. Finite Element Analysis (FEA) was used to optimize the pattern. A porosity of 53% and pore sizes in the range of 860 to 1500 μm were finally adopted. Tensile tests on porous samples were then carried out to validate the properties obtained numerically and identify the failure modes of the samples. Finally, FE elastoplastic analyses were performed on the porous samples in order to propose a failure criterion for the design of porous substitutes.

  5. [Development of a Novel Body Phantom with Bone Equivalent Density for Evaluation of Bone SPECT].

    Science.gov (United States)

    Ichikawa, Hajime; Miwa, Kenta; Matsutomo, Norikazu; Watanabe, Yoichi; Kato, Toyohiro; Shimada, Hideki

    2015-12-01

    We developed a custom-designed phantom for bone single photon emission computed tomography (SPECT)-specific radioactivity distribution and linear attenuation coefficient. The aim of this study was to evaluate the accuracy of the phantom. The lumbar phantom consisted of the trunk of a body phantom (background) containing a cylinder (vertebral body), a sphere (tumor), and a T-shaped container (processus). The vertebral body, tumor, and processus phantoms contained a K(2)HPO(4) solution of bone equivalent density and 50, 300 and 50 kBq/mL of (99m)Tc, respectively. The body phantom contained 8 kBq/mL of (99m)Tc solution. SPECT images were acquired using low-energy high-resolution collimation, a 128 × 128 matrix and 120 projections over 360° with a dwell time of 15 sec/view × 4 times. Thereafter, CT images were acquired at 130 kV and 70 ref mAs using adaptive dose modulation. The SPECT data were reconstructed with ordered subset expectation maximization with three-dimensional, scatter, and CT-based attenuation correction. Count ratio, linear attenuation coefficient (LAC), and full-width at half-maximum (FWHM) were measured. Count ratios between the background, the vertebral body, and the tumor in SPECT images were 463.8: 2888.0: 15150.3 (1: 6.23: 32.7). The LAC of the background and vertebral body in the CT-derived attenuation map were 0.155 cm⁻¹ and 0.284 cm⁻¹, respectively, and the FWHM measured from the processus was 15.27 mm. The precise counts and LAC indicated that the phantom was accurate and could serve as a tool for evaluating acquisition, reconstruction parameters, and quantitation in bone SPECT images.

  6. Growth and differentiation of a long bone in limb development, repair and regeneration.

    Science.gov (United States)

    Egawa, Shiro; Miura, Shinichirou; Yokoyama, Hitoshi; Endo, Tetsuya; Tamura, Koji

    2014-06-01

    Repair from traumatic bone fracture is a complex process that includes mechanisms of bone development and bone homeostasis. Thus, elucidation of the cellular/molecular basis of bone formation in skeletal development would provide valuable information on fracture repair and would lead to successful skeletal regeneration after limb amputation, which never occurs in mammals. Elucidation of the basis of epimorphic limb regeneration in amphibians would also provide insights into skeletal regeneration in mammals, since the epimorphic regeneration enables an amputated limb to re-develop the three-dimensional structure of bones. In the processes of bone development, repair and regeneration, growth of the bone is achieved through several events including not only cell proliferation but also aggregation of mesenchymal cells, enlargement of cells, deposition and accumulation of extracellular matrix, and bone remodeling.

  7. Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

    Science.gov (United States)

    Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness

    2017-03-30

    A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures.

  8. Development of bone marrow mesenchymal stem cell culture in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; PENG Li-pan; WU Nan; LI Le-ping

    2012-01-01

    Objective To review the in vitro development of bone marrow mesenchymal stem cells culture (BM-MSC).Data sources The data cited in this review were mainly obtained from articles listed in Medline and PubMed.The search terms were “bone marrow mesenchymal stem cell" and "cell culture".Study selection Articles regarding the in vitro development of BM-MSCs culture,as well as the challenge of optimizing cell culture environment in two-dimensional (2D) vs.3D.Results Improving the culture conditions increases the proliferation and reduces the differentiation.Optimal values for many culture parameters remain to be identified.Expansion of BM-MSCs under defined conditions remains challenging,including the development of optimal culture conditions for BMSC and large-volume production systems.Conclusions Expansion of BM-MSCs under defined conditions remains challenges,including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems.Optimal values for many culture parameters remain to be identified.

  9. New developments in calcium phosphate bone cements: approaching spinal applications

    OpenAIRE

    Vlad, Maria Daniela

    2009-01-01

    La presente tesis doctoral (i.e., “New developments in calcium phosphate bone cements: approaching spinal applications”) aporta nuevos conocimientos en el campo de los cementos óseos de fosfato de calcio (CPBCs) en relación a su aplicación clínica en el campo de la cirugía vertebral mínimamente invasiva. La hipótesis central de esta investigación fue formulada en los siguientes términos: “Los cementos apatíticos pueden ser (si se optimizan) una alternativa mejor (debido a sus propiedades d...

  10. Harold Goldstein (R) and Dan Leiser (L) discuss bone implant development in the the Shuttle Tile

    Science.gov (United States)

    1993-01-01

    Harold Goldstein (R) and Dan Leiser (L) discuss bone implant development in the the Shuttle Tile Laboratory N-242. A spin-off of Ames research on both bone density in microgravity and on thermal protection foams is the bone-growth implant shown in 1993.

  11. Development of monetite-nanosilica bone cement: a preliminary study.

    Science.gov (United States)

    Zhou, Huan; Luchini, Timothy J F; Agarwal, Anand K; Goel, Vijay K; Bhaduri, Sarit B

    2014-11-01

    In this paper, we reported the results of our efforts in developing DCPA/nanosilica composite orthopedic cement. It is motivated by the significances of DCPA and silicon in bone physiological activities. More specifically, this paper examined the effects of various experimental parameters on the properties of such composite cements. In this work, DCPA cement powders were synthesized using a microwave synthesis technique. Mixing colloidal nanosilica directly with synthesized DCPA cement powders can significantly reduce the washout resistance of DCPA cement. In contrast, a DCPA-nanosilica cement powder prepared by reacting Ca(OH)2 , H3 PO4 and nanosilica together showed good washout resistance. The incorporation of nanosilica in DCPA can improve compressive strength, accelerate cement solidification, and intensify surface bioactivity. In addition, it was observed that by controlling the content of NaHCO3 during cement preparation, the resulting composite cement properties could be modified. Allowing for the development of different setting times, mechanical performance and crystal features. It is suggested that DCPA-nanosilica composite cement can be a potential candidate for bone healing applications.

  12. Role of Thyroid Hormones in Skeletal Development and Bone Maintenance.

    Science.gov (United States)

    Bassett, J H Duncan; Williams, Graham R

    2016-04-01

    The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art.

  13. Bone development in black ducks as affected by dietary toxaphene

    Science.gov (United States)

    Mehrle, P.M.; Finley, M.T.; Ludke, J.L.; Mayer, F.L.; Kaiser, T.E.

    1979-01-01

    Black ducks, Anas rubripes, were exposed to dietary toxaphene concentrations of 0, 10, or 50 μg/g of food for 90 days prior to laying and through the reproductive season. Toxaphene did not affect reproduction or survival, but reduced growth and impaired backbone development in ducklings. Collagen, the organic matrix of bone, was decreased significantly in cervical vertebrae of ducklings fed 50 μg/g, and calcium conentrations increased in vertebrae of ducklings fed 10 or 50 μg/g. The effects of toxaphene were observed only in female ducklings. In contrast to effects on vertebrae, toxaphene exposure did not alter tibia development. Toxaphene residues in carcasses of these ducklings averaged slightly less than the dietary levels.

  14. Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Shuko Tokuriki

    2016-01-01

    Full Text Available Objective. To use cortical bone thickness (CBT of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA. The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures.

  15. The bone-anchored hearing aid for children: recent developments.

    NARCIS (Netherlands)

    Snik, A.F.M.; Leijendeckers, J.M.; Hol, M.K.S.; Mylanus, E.A.M.; Cremers, C.

    2008-01-01

    In 1984 the Bone-Anchored Hearing Aid, or BAHA, system was introduced. Its transducer is coupled directly to the skull percutaneously to form a highly effective bone-conduction hearing device. Clinical studies on adults with conductive hearing loss have shown that the BAHA system outperforms convent

  16. Development of Composite Scaffolds for Load Bearing Segmental Bone Defects

    Science.gov (United States)

    2013-07-01

    composite scaffolds designed to serve as bone regenerative therapies . We analyzed the benefits and drawbacks of different composite scaffold...related to fractures, sport and blast injuries. Diseases include bone cancer (osteosarcoma), tumor resection and reconstruction, osteoporosis ...selection for the scaffold has a direct impact on the biological and physical properties of the construct, there are some factors contributing to the

  17. Bone cements for percutaneous vertebroplasty and balloon kyphoplasty: Current status and future developments

    Directory of Open Access Journals (Sweden)

    Zhiwei He

    2015-01-01

    Full Text Available Osteoporotic vertebral compression fractures (OVCFs have gradually evolved into a serious health care problem globally. In order to reduce the morbidity of OVCF patients and improve their life quality, two minimally invasive surgery procedures, vertebroplasty (VP and balloon kyphoplasty (BKP, have been developed. Both VP and BKP require the injection of bone cement into the vertebrae of patients to stabilize fractured vertebra. As such, bone cement as the filling material plays an essential role in the effectiveness of these treatments. In this review article, we summarize the bone cements that are currently available in the market and those still under development. Two major categories of bone cements, nondegradable acrylic bone cements (ABCs and degradable calcium phosphate cements (CPCs, are introduced in detail. We also provide our perspectives on the future development of bone cements for VP and BKP.

  18. Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

    Science.gov (United States)

    Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

    2013-11-01

    Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

  19. 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.

  20. Evaluation of bone targeting salmon calcitonin analogues in rats developing osteoporosis and adjuvant arthritis.

    Science.gov (United States)

    Bhandari, Krishna H; Asghar, Waheed; Newa, Madhuri; Jamali, Fakhreddin; Doschak, Michael R

    2015-01-01

    Synthetic analogues of the peptide hormone calcitonin have been used in medicine as biologic drug therapies for decades, to treat pathological conditions of excessive bone turnover, such as osteoporosis, where more bones are removed than replaced during bone remodeling. Osteoporosis and other chronic skeletal diseases, including inflammatory arthritis, exact a substantial and growing toll on aging populations worldwide however they respond poor to synthetic biologic drug therapy, due in part to the rapid half-life of elimination, which for calcitonin is 43 minutes. To address those shortcomings, we have developed and synthesized bone-targeting variants of calcitonin as a targeted drug delivery strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in highly specific reaction conditions. To evaluate their in vivo efficacy, bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and dose escalation was performed in female rats developing Osteoporosis. The bone-targeting calcitonin analogues were also tested in a separate cohort of male rats developing adjuvant-induced arthritis. Ovariectomized female rats developing Osteoporosis were administered daily sub-cutaneous injection of analogues equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis was developed in male rats by administering Mycobacterium butyricum through tail base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg of calcitonin was administered and the rats were measured for visible signs of inflammation to a 21 day endpoint. In both studies, the effect of drug intervention upon bone volume and bone mineral density (BMD) was assessed by measuring the trabecular bone volume percentage and BMD at the proximal tibial metaphysis using in vivo micro-computed tomography. With dose escalation studies, only bone targeting analogue dosed groups

  1. Development of monetite/phosphorylated chitosan composite bone cement.

    Science.gov (United States)

    Boroujeni, Nariman Mansouri; Zhou, Huan; Luchini, Timothy J F; Bhaduri, Sarit B

    2014-02-01

    In this article, we report the development of a biodegradable monetite [dicalcium phosphate anhydrous (DCPA), CaHPO4 ]/phosphorylated chitosan (p-chitosan) composite orthopedic cement. The cement pastes showed desirable handling properties, injectability, and washout resistance. The incorporation of p-chitosan powders at 5 wt % shortened the setting time of DCPA and significantly improved the mechanical performance of DCPA cement, increasing the compressive strength almost twice from 11.09 ± 1.85 MPa at 0% chitosan to 23.43 ± 1.47 MPa at 5 wt % p-chitosan. On the other hand, higher p-chitosan content or untreated chitosan incorporation lowered the performance of DCPA cements. The cytocompatibility of the composite cement was investigated in vitro using the preosteoblast cell line MC3T3-E1. An increase in cell proliferation was observed in both DCPA and DCPA-p-chitosan. The results show that both the materials are as cytocompatible as hydroxyapatite. Based on these results, DCPA-p-chitosan composite cement can be considered as potential bone repair material.

  2. On the development of an apatitic calcium phosphate bone cement

    Indian Academy of Sciences (India)

    Manoj Komath; H K Varma; R Sivakumar

    2000-04-01

    Development of an apatitic calcium phosphate bone cement is reported. 100 Particles of tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) were mixed in equimolar ratio to form the cement powder. The wetting medium used was distilled water with Na2HPO4 as accelerator to manipulate the setting time. The cement powder, on wetting with the medium, formed a workable putty. The setting times of the putty were measured using a Vicat type apparatus and the compressive strength was determined with a Universal Testing Machine. The nature of the precipitated cement was analyzed through X-ray diffraction (XRD), fourier transform infrared spectrometry (FTIR) and energy dispersive electron microprobe (EDAX). The results showed the phase to be apatitic with a calcium–to–phosphorous ratio close to that of hydroxyapatite. The microstructure analysis using scanning electron microscopy (SEM) showed hydroxyapatite nanocrystallite growth over particulate matrix surface. The structure has an apparent porosity of ∼ 52%. There were no appreciable dimensional or thermal changes during setting. The cement passed the in vitro toxicological screening (cytotoxicity and haemolysis) tests. Optimization of the cement was done by manipulating the accelerator concentration so that the setting time, hardening time and the compressive strength had clinically relevant values.

  3. The role of the perichondrium in fetal bone development.

    Science.gov (United States)

    Kronenberg, Henry M

    2007-11-01

    Most cells in mesenchymal condensations that form endochondral bone become chondrocytes; cells at the outer edges of the condensations, however, become perichondrial cells with distinct properties and functions. Some perichondrial cells become osteoblasts that populate both the future cortical and trabecular bone; others probably become chondrocytes. Perichondrial cells both send signals to the underlying growth cartilage and receive signals from the cartilage. Here I illustrate briefly examples of the complicated interactions between the perichondrium and the underlying growth cartilage.

  4. Development of Raman spectral markers to assess metastatic bone in breast cancer

    Science.gov (United States)

    Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

    2014-11-01

    Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

  5. Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development.

    Science.gov (United States)

    Badri, Mohammed K; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Haruko; Ray, Manas; Scott, Greg; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

    2016-08-01

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ∼20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Alexander M Tatara

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

  7. Radiographic aluminum equivalent value of bone : the development of a registration method and some clinical applications

    NARCIS (Netherlands)

    W.T. Trouerbach (Willem)

    1982-01-01

    textabstractThe aim of this thesis is to establish and develop a method suitable for obtaining an objective analysis of bone as registered on a radiographic image. This analysis concerns determination of the quantity of bone mineral present. The system has been tested in-vitro and in a clinical stud

  8. Development of Nano-biomaterials for Bone Repair

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A new kind of nano-biomaterials of nano apatite ( NA ) and polyamide8063 ( PA ) composite was prepared by direct using NA slurry. The experimental results showed that the NA content in the composite was similar to that of natural bone. Interface chemical bonding was formed between NA and PA. The NA keeps the original morphological structure with a crystal size of 10- 30 nm in width by 50- 90 nm in length with a ratio of~ 2.5 and distributed uniformly in the polymer. The synthetic nano-biomaterials could be one of the best bioactive materials for load-bearing bone repair or substitution materials.

  9. Silicon in broiler drinking water promotes bone development in broiler chickens.

    Science.gov (United States)

    Sgavioli, S; de Faria Domingues, C H; Castiblanco, D M C; Praes, M F F M; Andrade-Garcia, Giuliana M; Santos, E T; Baraldi-Artoni, S M; Garcia, R G; Junqueira, O M

    2016-10-01

    Skeletal abnormalities, bone deformities and fractures cause significant losses in broiler production during both rearing and processing. Silicon is an essential mineral for bone and connective tissue synthesis and for calcium absorption during the early stages of bone formation. Performance was not affected by the addition of silicon. However, broilers receiving silicon showed a significant increase of phosphorus, zinc, copper, manganese and ash in the tibia. In conclusion, broiler performance was not impaired by adding the tested silicon product to the drinking water. In addition, bone development improved, as demonstrated by higher mineral and ash content. Further studies are required to determine the optimal concentration of silicon, including heat stress simulations, to better understand the effects of silicon on bone development.

  10. Development of forelimb bones in indigenous sheep fetuses

    Directory of Open Access Journals (Sweden)

    N. S. Ahmed

    2008-01-01

    Full Text Available The study included detection of the sites of ossification centers and their sequence of appearance in the forelimb bones of indigenous sheep fetuses by using double staining method with younger specimens and radiography or maceration methods with old specimens, as well as, histological study with some ages. The results showed that the primary ossification centers of the forelimb in indigenous sheep fetuses appeared firstly in the diaphyses of radius and ulna, humerus, scapula, metacarpus, phalanges and lastly in the carpal bone at an estimated age of 43, 45, 46, 47, 49 - 56 and 90-118 days old respectively. The results of statistical analysis of the total lengths of scapula, humerus, radius, ulna and metacarpus with the lengths of their ossified parts through the 7th – 15th weeks of fetus age, showed presence of significant differences in the average of these measurements among most of studied weeks. Also there was a significant differences in the average of relative increase in the total length and length of ossified part of diaphysis of studied bones during the 7th week in comparison to the same average in the other studied weeks (8th-15th week of indigenous sheep fetuses age.

  11. Linking bone development on the caudal aspect of the distal phalanx with lameness during life.

    Science.gov (United States)

    Newsome, R; Green, M J; Bell, N J; Chagunda, M G G; Mason, C S; Rutland, C S; Sturrock, C J; Whay, H R; Huxley, J N

    2016-06-01

    Claw horn disruption lesions (CHDL; sole hemorrhage, sole ulcer, and white line disease) cause a large proportion of lameness in dairy cattle, yet their etiopathogenesis remains poorly understood. Untreated CHDL may be associated with damage to the internal anatomy of the foot, including to the caudal aspect of the distal phalanx upon which bone developments have been reported with age and with sole ulcers at slaughter. The primary aim of this study was to assess whether bone development was associated with poor locomotion and occurrence of CHDL during a cow's life. A retrospective cohort study imaged 282 hind claws from 72 Holstein-Friesian dairy cows culled from a research herd using X-ray micro-computed tomography (μ-CT; resolution: 0.11mm). Four measures of bone development were taken from the caudal aspect of each distal phalanx, in caudal, ventral, and dorsal directions, and combined within each claw. Cow-level variables were constructed to quantify the average bone development on all hind feet (BD-Ave) and bone development on the most severely affected claw (BD-Max). Weekly locomotion scores (1-5 scale) were available from first calving. The variables BD-Ave and BD-Max were used as outcomes in linear regression models; the explanatory variables included locomotion score during life, age, binary variables denoting lifetime occurrence of CHDL and of infectious causes of lameness, and other cow variables. Both BD-Max and BD-Ave increased with age, CHDL occurrence, and an increasing proportion of locomotion scores at which a cow was lame (score 4 or 5). The models estimated that BD-Max would be 9.8mm (SE 3.9) greater in cows that had been lame at >50% of scores within the 12mo before slaughter (compared with cows that had been assigned no lame scores during the same period), or 7.0mm (SE 2.2) greater if the cow had been treated for a CHDL during life (compared with cows that had not). Additionally, histology demonstrated that new bone development was osteoma

  12. Development and Implementation of Instrumentation System for Diagnosing Bone Quality using Vibration Technique

    Directory of Open Access Journals (Sweden)

    Mrs.S.Mythili

    2014-01-01

    Full Text Available In this paper, the development of Instrumentation system for diagnosing the condition of bone quality is discussed. The conventionally available method for the assessment of bone mineral density and its related disease is through DEXA SCAN and cost of this machine is more for every scan which is not affordable for all people . This work is based on vibration analysis from impulse input on human leg bone. Two commercial MEMS accelerometers are attached on the shaft (long vertical leg bone at appropriate locations where vibrations are predominant. The proposed system consists of a MEMS accelerometer sensor ADXL335 from Analog Devices is used as a detection sensor that measures vibrations in terms of acceleration produced by mild impulsive force applied on the diaphysis of left tibia and interfaced with Data Acquisition Card (DAQ and displayed in the PC. The experiment was performed on human subjects by applying impulsive force using automated hammer in order to excite the bone with uniform force consistently in all trials. The time and the frequency domain analysis of the obtained output signals (analog voltages proportional to the accelerations from two sensors gives the useful information about the BMD of the human subjects. The results have shown that the accelerations obtained in terms of voltages from the excitations of bone is different for men and women with different age groups .The information acquired and analyzed is used to evaluate the quality of the bone.

  13. Development and Characterization of a Bioinspired Bone Matrix with Aligned Nanocrystalline Hydroxyapatite on Collagen Nanofibers

    Directory of Open Access Journals (Sweden)

    Hsi-Chin Wu

    2016-03-01

    Full Text Available Various kinds of three-dimensional (3D scaffolds have been designed to mimic the biological spontaneous bone formation characteristics by providing a suitable microenvironment for osteogenesis. In view of this, a natural bone-liked composite scaffold, which was combined with inorganic (hydroxyapatite, Hap and organic (type I collagen, Col phases, has been developed through a self-assembly process. This 3D porous scaffold consisting of a c-axis of Hap nanocrystals (nHap aligning along Col fibrils arrangement is similar to natural bone architecture. A significant increase in mechanical strength and elastic modulus of nHap/Col scaffold is achieved through biomimetic mineralization process when compared with simple mixture of collagen and hydroxyapatite method. It is suggested that the self-organization of Hap and Col produced in vivo could also be achieved in vitro. The oriented nHap/Col composite not only possesses bone-like microstructure and adequate mechanical properties but also enhances the regeneration and reorganization abilities of bone tissue. These results demonstrated that biomimetic nHap/Col can be successfully reconstructed as a bone graft substitute in bone tissue engineering.

  14. Effects of Maternal Hypoxia during Pregnancy on Bone Development in Offspring: A Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    Alice M. C. Lee

    2014-01-01

    Full Text Available Low birth weight is associated with reduced bone mass and density in adult life. However, effects of maternal hypoxia (MH on offspring bone development are not known. Objective. The current study investigated the effects of fetal growth restriction induced by MH during the last half of gestation on bone structure and volume in the offspring of the fetus near term and the pup in adolescence. Methods. During 35–62-day gestation (term, 69d, guinea pigs were housed in room air (21% O2; control or 12% O2 (MH. Offspring femur and tibia were collected at 62d gestation and 120d after birth. Results. MH decreased fetal birth weight but did not affect osteogenic potential pools in the fetal bone marrow. Histological analysis showed no effects of MH on tibial growth plate thickness in either fetal or postnatal offspring, although there was increased VEGF mRNA expression in the growth plate of postnatal offspring. MH did not change primary spongiosa height but lowered collagen-1 mRNA expression in postnatal offspring. There was increased mRNA expression of adipogenesis-related gene (FABP4 in bone from the MH postnatal offspring. Conclusion. MH during late gestation did not change the pool of osteogenic cells before birth or growth plate heights before and after birth. However, MH reduced expression of bone formation marker (collagen-1 and increased expression of fat formation marker (FABP4 in postnatal offspring bone.

  15. Development of a Three-Dimensional (3D Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft

    Directory of Open Access Journals (Sweden)

    Ying-Chao Chou

    2016-04-01

    Full Text Available This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

  16. Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

    Science.gov (United States)

    Chou, Ying-Chao; Lee, Demei; Chang, Tzu-Min; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung; Ueng, Steve Wen-Neng

    2016-04-20

    This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

  17. Effects of growth hormone (GH) transgene and nutrition on growth and bone development in common carp.

    Science.gov (United States)

    Zhu, Tingbing; Zhang, Tanglin; Wang, Yaping; Chen, Yushun; Hu, Wei; Zhu, Zuoyan

    2013-10-01

    Limited information is available on effects of growth hormone transgene and nutrition on growth and development of aquatic animals. Here, we present a study to test these effects with growth-enhanced transgenic common carp under two nutritional conditions or feeding rations (i.e., 5% and 10% of fish body weight per day). Compared with the nontransgenic fish, the growth rates of the transgenic fish increased significantly in both feeding rations. The shape of the pharyngeal bone was similar among treatments, but the transgenic fish had relatively smaller and lighter pharyngeal bone compared with the nontransgenic fish. Calcium content of the pharyngeal bone of the transgenic fish was significantly lower than that of the nontransgenic fish. Feeding ration also affected growth rate but less of an effect on bone development. By manipulating intrinsic growth and controlling for both environment (e.g., feeding ration) and genetic background or genotype (e.g., transgenic or not), this study provides empirical evidence that the genotype has a stronger effect than the environment on pharyngeal bone development. The pharyngeal bone strength could be reduced by decreased calcium content and calcification in the transgenic carp.

  18. Osteoclast activity modulates B-cell development in the bone marrow

    Institute of Scientific and Technical Information of China (English)

    Anna Mansour; Adrienne Anginot; Stéphane J C Mancini; Claudine Schiff; Georges F Carle; Abdelilah Wakkach; Claudine Blin-Wakkach

    2011-01-01

    B-cell development is dependent on the interactions between B-cell precursors and bone marrow stromal cells, but the role of osteoclasts (OCLs) in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid (ZA), an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone microenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity.

  19. Osteoclast activity modulates B-cell development in the bone marrow.

    Science.gov (United States)

    Mansour, Anna; Anginot, Adrienne; Mancini, Stéphane J C; Schiff, Claudine; Carle, Georges F; Wakkach, Abdelilah; Blin-Wakkach, Claudine

    2011-07-01

    B-cell development is dependent on the interactions between B-cell precursors and bone marrow stromal cells, but the role of osteoclasts (OCLs) in this process remains unknown. B lymphocytopenia is a characteristic of osteopetrosis, suggesting a modulation of B lymphopoiesis by OCL activity. To address this question, we first rescued OCL function in osteopetrotic oc/oc mice by dendritic cell transfer, leading to a restoration of both bone phenotype and B-cell development. To further explore the link between OCL activity and B lymphopoiesis, we induced osteopetrosis in normal mice by injections of zoledronic acid (ZA), an inhibitor of bone resorption. B-cell number decreased specifically in the bone marrow of ZA-treated mice. ZA did not directly affect B-cell differentiation, proliferation and apoptosis, but induced a decrease in the expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement. Equivalent low osteoblastic engagement in oc/oc mice confirmed that it resulted from the reduced OCL activity rather than from a direct effect of ZA on osteoblasts. These dramatic alterations of the bone microenvironment were disadvantageous for B lymphopoiesis, leading to retention of B-cell progenitors outside of their bone marrow niches in the ZA-induced osteopetrotic model. Altogether, our data revealed that OCLs modulate B-cell development in the bone marrow by controlling the bone microenvironment and the fate of osteoblasts. They provide novel basis for the regulation of the retention of B cells in their niche by OCL activity.

  20. Autoclaved Tumor Bone for Skeletal Reconstruction in Paediatric Patients: A Low Cost Alternative in Developing Countries

    Directory of Open Access Journals (Sweden)

    Masood Umer

    2013-01-01

    Full Text Available We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1 wide en bloc resection of the tumor; (2 curettage of tumor from the resected bone; (3 autoclaving for 8 minutes (4 bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used; (5 reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months, 31 patients had recovered without any complications. Thirty-eight patients successfully achieved a solid bony union between the graft and recipient bone. Three patients had surgical site infection. They were managed with wound debridement and flap coverage of the defect. Local recurrence and nonunion occurred in two patients each. One patient underwent disarticulation at hip due to extensive local disease and one died of metastasis. For patients with non-union, revision procedure with bone graft and compression plates was successfully used. The use of autoclaved tumor grafts provides a limb salvage option that is inexpensive and independent of external resources and is a viable option for musculoskeletal tumor management in developing countries.

  1. Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility.

    Science.gov (United States)

    Lu, Yongtao; Boudiffa, Maya; Dall'Ara, Enrico; Bellantuono, Ilaria; Viceconti, Marco

    2016-07-01

    In vivo micro-computed tomography (µCT) scanning of small rodents is a powerful method for longitudinal monitoring of bone adaptation. However, the life-time bone growth in small rodents makes it a challenge to quantify local bone adaptation. Therefore, the aim of this study was to develop a protocol, which can take into account large bone growth, to quantify local bone adaptations over space and time. The entire right tibiae of eight 14-week-old C57BL/6J female mice were consecutively scanned four times in an in vivo µCT scanner using a nominal isotropic image voxel size of 10.4µm. The repeated scan image datasets were aligned to the corresponding baseline (first) scan image dataset using rigid registration. 80% of tibia length (starting from the endpoint of the proximal growth plate) was selected as the volume of interest and partitioned into 40 regions along the tibial long axis (10 divisions) and in the cross-section (4 sectors). The bone mineral content (BMC) was used to quantify bone adaptation and was calculated in each region. All local BMCs have precision errors (PE%CV) of less than 3.5% (24 out of 40 regions have PE%CV of less than 2%), least significant changes (LSCs) of less than 3.8%, and 38 out of 40 regions have intraclass correlation coefficients (ICCs) of over 0.8. The proposed protocol allows to quantify local bone adaptations over an entire tibia in longitudinal studies, with a high reproducibility, an essential requirement to reduce the number of animals to achieve the necessary statistical power.

  2. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    cells (from about 45% to 25%), evidently as a result of the severely changed microenvironment. In this study we have demonstrated in vivo the development of an acidic and hypoxic bone marrow hampering normal haemopoiesis during leukaemic growth. Our data support the notion of BNML as a valuable tool......The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...

  3. Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

    Science.gov (United States)

    Chen, Shan; Grover, Monica; Sibai, Tarek; Black, Jennifer; Rianon, Nahid; Rajagopal, Abbhirami; Munivez, Elda; Bertin, Terry; Dawson, Brian; Chen, Yuqing; Jiang, Ming-Ming; Lee, Brendan; Yang, Tao; Bae, Yangjin

    2015-05-01

    Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development.

  4. Development of [{sup 90}Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)], E-mail: kogawa@med.kanazawa-u.ac.jp; Kawashima, Hidekazu [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Washiyama, Kohshin; Yoshimoto, Mitsuyoshi [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942 (Japan); Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Ueda, Masashi [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Mori, Hirofumi [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Saji, Hideo [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2009-02-15

    Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed {sup 186}Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed {sup 90}Y-labeled radiopharmaceutical could be developed. Methods: In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [{sup 90}Y]DOTA-complex-conjugated bisphosphonate ([{sup 90}Y]DOTA-HBP) was prepared by coordination with {sup 90}Y, and its biodistribution was studied in comparison to [{sup 90}Y]citrate. Results: In biodistribution experiments, [{sup 90}Y]DOTA-HBP and [{sup 90}Y]citrate rapidly accumulated and resided in the bone. Although [{sup 90}Y]citrate showed a higher level of accumulation in the bone than [{sup 90}Y]DOTA-HBP, the clearances of [{sup 90}Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [{sup 90}Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [{sup 90}Y]DOTA-HBP were lower than those of [{sup 90}Y]citrate. Conclusions: [{sup 90}Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [{sup 90}Y]citrate. Since the DOTA ligand forms a stable complex not only with {sup 90}Y but also with lutetium ({sup 177}Lu), indium ({sup 111}In), gallium ({sup 67/68}Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging.

  5. Bone Signaling in Middle Ear Development: A Genome‐Wide Differential Expression Analysis

    DEFF Research Database (Denmark)

    Nielsen, Michelle Christine; Bertelsen, Tomas Martin; Friis, Morten;

    2014-01-01

    Common middle ear diseases may affect bone behavior in the middle ear air cell system. To understand this pathologic pneumatization, the normal development of bone in the middle ear should be investigated. The objective of this study was to analyze gene expression of bone‐related signaling factors...... and gene sets in the developing middle ear. Microarray technology was used to identify bone‐related genes and gene sets, which were differentially expressed between the lining tissue of adult (quiescent) bulla and young (resorbing/forming) bulla. Data were analyzed using tools of bioinformatics...... and expression levels of selected genes were validated using quantitative polymerase chain reaction. The candidate gene products were compared with previously published data on middle ear bone metabolism. No differentially expressed genes were found on the outer surface of bulla. On the inner lining a total...

  6. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  7. Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.

    Science.gov (United States)

    Pereira, Aline D'Avila; Ribeiro, Danielle Cavalcante; de Santana, Fernanda Carvalho; de Sousa Dos Santos, Aline; Mancini-Filho, Jorge; do Nascimento-Saba, Celly Cristina Alves; Velarde, Luis Guillermo Coca; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-08-01

    Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.

  8. Characterization of zebrafish mutants with defects in bone calcification during development.

    Science.gov (United States)

    Xi, Yang; Chen, Dongyan; Sun, Lei; Li, Yuhao; Li, Lei

    2013-10-11

    Using the fluorescent dyes calcein and alcian blue, we stained the F3 generation of chemically (ENU) mutagenized zebrafish embryos and larvae, and screened for mutants with defects in bone development. We identified a mutant line, bone calcification slow (bcs), which showed delayed axial vertebra calcification during development. Before 4-5 days post-fertilization (dpf), the bcs embryos did not display obvious abnormalities in bone development (i.e., normal number, size and shape of cartilage and vertebrae). At 5-6 dpf, when vertebrae calcification starts, bcs embryos began to show defects. At 7 dpf, for example, in most of the bcs embryos examined, calcein staining revealed no signals of vertebrae mineralization, whereas during the same developmental stages, 2-14 mineralized vertebrae were observed in wild-type animals. Decreases in the number of calcified vertebrae were also observed in bcs mutants when examined at 9 and 11 dpf, respectively. Interestingly, by 13 dpf the defects in bcs mutants were no longer evident. There were no significant differences in the number of calcified vertebrae between wild-type and mutant animals. We examined the expression of bone development marker genes (e.g., Sox9b, Bmp2b, and Cyp26b1, which play important roles in bone formation and calcification). In mutant fish, we observed slight increases in Sox9b expression, no alterations in Bmp2b expression, but significant increases in Cyp26b1 expression. Together, the data suggest that bcs delays axial skeletal calcification, but does not affect bone formation and maturation.

  9. A novel composite material specifically developed for ultrasound bone phantoms: cortical, trabecular and skull.

    Science.gov (United States)

    Wydra, A; Maev, R Gr

    2013-11-21

    In the various stages of developing diagnostic and therapeutic equipment, the use of phantoms can play a very important role in improving the process, help in implementation, testing and calibrations. Phantoms are especially useful in developing new applications and training new doctors in medical schools. However, devices that use different physical factors, such as MRI, Ultrasound, CT Scan, etc will require the phantom to be made of different physical properties. In this paper we introduce the properties of recently designed new materials for developing phantoms for ultrasonic human body investigation, which in today's market make up more than 30% in the world of phantoms. We developed a novel composite material which allows fabrication of various kinds of ultrasound bone phantoms to mimic most of the acoustical properties of human bones. In contrast to the ex vivo tissues, the proposed material can maintain the physical and acoustical properties unchanged for long periods of time; moreover, these properties can be custom designed and created to suit specific needs. As a result, we introduce three examples of ultrasound phantoms that we manufactured in our laboratory: cortical, trabecular and skull bone phantoms. The paper also presents the results of a comparison study between the acoustical and physical properties of actual human bones (reported in the referenced literatures) and the phantoms manufactured by us.

  10. [Importance of bone scanning and osteoscintimetry for assessing development of acute haematogenic childhood osteomyelitis (author's transl)].

    Science.gov (United States)

    Fotter, R; Höllwarth, M

    1980-01-01

    Bone scanning with 99m-Tc-MDP is generally used for the early diagnosis of acute haematogenic childhood osteomyelitis. The combination of this method with radionuclide osteoscintimetry and the evaluation of the relative uptake ratio supply objective criteria for assessing the development of the disease. They permit statements as to the morphological and functional aspects of the disease and thus facilitate clinical assessment.

  11. Development and characterization of a rabbit alveolar bone nonhealing defect model.

    NARCIS (Netherlands)

    Young, S.; Bashoura, A.G.; Borden, T.; Baggett, L.S.; Jansen, J.A.; Wong, M.; Mikos, A.G.

    2008-01-01

    The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 1

  12. Development of bioactive porous α-TCP/HAp beads for bone tissue engineering.

    Science.gov (United States)

    Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi

    2013-11-01

    Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, α-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, α-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained α-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that α-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed α-TCP/HAp beads are a promising tool for bone tissue engineering.

  13. Methodology developed for the simultaneous measurement of bone formation and bone resorption in rats based on the pharmacokinetics of fluoride.

    Science.gov (United States)

    Lupo, Maela; Brance, Maria Lorena; Fina, Brenda Lorena; Brun, Lucas Ricardo; Rigalli, Alfredo

    2015-01-01

    This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date.

  14. Infant bone age estimation based on fibular shaft length: model development and clinical validation

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Andy; Stamoulis, Catherine; Bixby, Sarah D.; Breen, Micheal A.; Connolly, Susan A.; Kleinman, Paul K. [Boston Children' s Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2016-03-15

    Bone age in infants (<1 year old) is generally estimated using hand/wrist or knee radiographs, or by counting ossification centers. The accuracy and reproducibility of these techniques are largely unknown. To develop and validate an infant bone age estimation technique using fibular shaft length and compare it to conventional methods. We retrospectively reviewed negative skeletal surveys of 247 term-born low-risk-of-abuse infants (no persistent child protection team concerns) from July 2005 to February 2013, and randomized them into two datasets: (1) model development (n = 123) and (2) model testing (n = 124). Three pediatric radiologists measured all fibular shaft lengths. An ordinary linear regression model was fitted to dataset 1, and the model was evaluated using dataset 2. Readers also estimated infant bone ages in dataset 2 using (1) the hemiskeleton method of Sontag, (2) the hemiskeleton method of Elgenmark, (3) the hand/wrist atlas of Greulich and Pyle, and (4) the knee atlas of Pyle and Hoerr. For validation, we selected lower-extremity radiographs of 114 normal infants with no suspicion of abuse. Readers measured the fibulas and also estimated bone ages using the knee atlas. Bone age estimates from the proposed method were compared to the other methods. The proposed method outperformed all other methods in accuracy and reproducibility. Its accuracy was similar for the testing and validating datasets, with root-mean-square error of 36 days and 37 days; mean absolute error of 28 days and 31 days; and error variability of 22 days and 20 days, respectively. This study provides strong support for an infant bone age estimation technique based on fibular shaft length as a more accurate alternative to conventional methods. (orig.)

  15. Hedgehog信号通路与骨发育%Hedgehog signaling pathway and bone development

    Institute of Scientific and Technical Information of China (English)

    邹沙沙; 胡洪亮

    2011-01-01

    背景:Hedgehog作为骨发育中一种重要调控因子,近几年其在骨生长中作用机制的研究备受关注.目的:介绍Hedgehog在软骨组织和骨组织发育中的作用机制及其与骨疾病的关系,从而分析Hedgehog信号通路与骨发育的研究现状及发展趋势.方法:应用计算机检索中国期刊全文数据库和PubMed 数据库,以"Hedgehog,骨发育,间充质干细胞,软骨,成骨,骨缺陷"和"Hedgehog,bone development,mesenchymal stem cells,cartilage,osteogenesis,bone defects"为检索词.最终共纳入31篇文献进行综述.结果与结论:Hedgehog信号与骨发育各阶段密切相关,包括间充质细胞向骨细胞分化,软骨组织和骨组织形成等各方面.其信号通路传导异常会导致各种骨畸形或骨缺陷.但是Hedgehog信号在骨发育中的详细作用机制体系尚未完善,相关动物实验技术尚未成熟,国内外尚未出现相关临床实验.由于Hedgehog即参与骨发育,又参与某些胚胎组织的血管重新形成和成年哺乳动物的血管发生,因而有望在修复骨缺损的同时解决骨组织工程血管化的问题.Hedgehog信号通路的研究在骨组织工程及临床基因干预治疗等领域有广阔的前景.%BACKGROUND: Hedgehog, as an important regulatory factor in bone growth, has been recently focused for its mechanism inbone growth.OBJECTIVE: To introduce the mechanisms of Hedgehog in cartilage and skeleton development and the relationship between thehedgehog signalling pathway and bone disease and to investigate the research progress in Hedgehog signalling pathway in bonedevelopment.METHODS: A computer-based online search in PubMed and CNKI database was performed using key words of “Hedgehog, bonedevelopment, mesenchymal stem cells, cartilage, osteogenesis, bone defects” in English and Chinese respecti vely. The publisheddates are limited between January 1994 and December 2010. Researches related to this review purpose were included

  16. Msx1 expression regulation by its own antisense RNA: consequence on tooth development and bone regeneration.

    Science.gov (United States)

    Babajko, Sylvie; Petit, Stéphane; Fernandes, Isabelle; Méary, Fleur; LeBihan, Johanne; Pibouin, Laurence; Berdal, Ariane

    2009-01-01

    Msx homeogenes play an important role in epithelial-mesenchymal interactions leading development. Msx1 is relevant for dental and craniofacial morphogenesis, as suggested by phenotypes of Msx1 mutations in human and Msx1 KO mice. During adulthood, Msx1 is still expressed in the skeleton where its role is largely unknown. Our group showed that the Msx1 gene is submitted to bidirectional transcription generating a long noncoding antisense (AS) RNA. During tooth development, Msx1 sense (S) and AS RNAs showed specific patterns of expression. Thus, the aim of the present study was to analyze the relation between Msx1 S and AS RNAs. In vivo mapping in adult mice showed that both Msx1 RNAs were detected in tested tissues such as bone. In vitro, Msx1 AS RNA decreased endogenous Msx1 S expression and modified Msx1 protein cell distribution. Regulations of Dlx5 and Bmp4 expression involving Msx1 S and AS RNAs showed that Msx1 AS RNA could modulate Msx1 function. The study of Msx1 S and AS RNA status is interesting in the case of tooth agenesis and bone loss to see if a disturbance of this balance could be associated with a disturbance of bone homeostasis. In that sense, our current results suggest a clear involvement of Msx1 in alveolar bone.

  17. Methodologies for Development of Patient Specific Bone Models from Human Body CT Scans

    Science.gov (United States)

    Chougule, Vikas Narayan; Mulay, Arati Vinayak; Ahuja, Bharatkumar Bhagatraj

    2016-06-01

    This work deals with development of algorithm for physical replication of patient specific human bone and construction of corresponding implants/inserts RP models by using Reverse Engineering approach from non-invasive medical images for surgical purpose. In medical field, the volumetric data i.e. voxel and triangular facet based models are primarily used for bio-modelling and visualization, which requires huge memory space. On the other side, recent advances in Computer Aided Design (CAD) technology provides additional facilities/functions for design, prototyping and manufacturing of any object having freeform surfaces based on boundary representation techniques. This work presents a process to physical replication of 3D rapid prototyping (RP) physical models of human bone from various CAD modeling techniques developed by using 3D point cloud data which is obtained from non-invasive CT/MRI scans in DICOM 3.0 format. This point cloud data is used for construction of 3D CAD model by fitting B-spline curves through these points and then fitting surface between these curve networks by using swept blend techniques. This process also can be achieved by generating the triangular mesh directly from 3D point cloud data without developing any surface model using any commercial CAD software. The generated STL file from 3D point cloud data is used as a basic input for RP process. The Delaunay tetrahedralization approach is used to process the 3D point cloud data to obtain STL file. CT scan data of Metacarpus (human bone) is used as the case study for the generation of the 3D RP model. A 3D physical model of the human bone is generated on rapid prototyping machine and its virtual reality model is presented for visualization. The generated CAD model by different techniques is compared for the accuracy and reliability. The results of this research work are assessed for clinical reliability in replication of human bone in medical field.

  18. Development of bone-like zirconium oxide nanoceramic modified chitosan based porous nanocomposites for biomedical application.

    Science.gov (United States)

    Bhowmick, Arundhati; Pramanik, Nilkamal; Jana, Piyali; Mitra, Tapas; Gnanamani, Arumugam; Das, Manas; Kundu, Patit Paban

    2017-02-01

    Here, zirconium oxide nanoparticles (ZrO2 NPs) were incorporated for the first time in organic-inorganic hybrid composites containing chitosan, poly(ethylene glycol) and nano-hydroxypatite (CS-PEG-HA) to develop bone-like nanocomposites for bone tissue engineering application. These nanocomposites were characterized by FT-IR, XRD, TEM combined with SAED. SEM images and porosity measurements revealed highly porous structure having pore size of less than 1μm to 10μm. Enhanced water absorption capacity and mechanical strengths were obtained compared to previously reported CS-PEG-HA composite after addition of 0.1-0.3wt% of ZrO2 NPs into these nanocomposites. The mechanical strengths and porosities were similar to that of human spongy bone. Strong antimicrobial effects against gram-negative and gram-positive bacterial strains were also observed. Along with getting low alkalinity pH (7.4) values, similar to the pH of human plasma, hemocompatibility and cytocompatibility with osteoblastic MG-63 cells were also established for these nanocomposites. Addition of 15wt% HA-ZrO2 (having 0.3wt% ZrO2 NPs) into CS-PEG (55:30wt%) composite resulted in greatest mechanical strength, porosity, antimicrobial property and cytocompatibility along with suitable water absorption capacity and compatibility with human pH and blood. Thus, this nanocomposite could serve as a potential candidate to be used for bone tissue engineering.

  19. Flat bones and sutures formation in the human cranial vault during prenatal development and infancy: A computational model.

    Science.gov (United States)

    Burgos-Flórez, F J; Gavilán-Alfonso, M E; Garzón-Alvarado, D A

    2016-03-21

    The processes of flat bones growth, sutures formation and interdigitation in the human calvaria are controlled by a complex interaction between genetic, biochemical and environmental factors that regulate bone formation and resorption during prenatal development and infancy. Despite previous experimental evidence accounting for the role of the main biochemical factors acting on these processes, the underlying mechanisms controlling them are still unknown. Therefore, we propose a mathematical model of the processes of flat bone and suture formation, taking into account several biological events. First, we model the growth of the flat bones and the formation of sutures and fontanels as a reaction diffusion system between two proteins: TGF-β2 and TGF-β3. The former is expressed by osteoblasts and allows adjacent mesenchymal cells differentiation on the bone fronts of each flat bone. The latter is expressed by mesenchymal cells at the sutures and inhibits their differentiation into osteoblasts at the bone fronts. Suture interdigitation is modelled using a system of reaction diffusion equations that develops spatio-temporal patterns of bone formation and resorption by means of two molecules (Wnt and Sclerostin) which control mesenchymal cells differentiation into osteoblasts at these sites. The results of the computer simulations predict flat bone growth from ossification centers, sutures and fontanels formation as well as bone formation and resorption events along the sutures, giving rise to interdigitated patterns. These stages were modelled and solved by the finite elements method. The simulation results agree with the morphological characteristics of calvarial bones and sutures throughout human prenatal development and infancy.

  20. The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

    Directory of Open Access Journals (Sweden)

    Takahiro Tsutsumimoto

    2014-11-01

    Full Text Available Neuroblastoma (NB, which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2. In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB.

  1. Inter-dependent tissue growth and Turing patterning in a model for long bone development

    Science.gov (United States)

    Tanaka, Simon; Iber, Dagmar

    2013-10-01

    The development of long bones requires a sophisticated spatial organization of cellular signalling, proliferation, and differentiation programs. How such spatial organization emerges on the growing long bone domain is still unresolved. Based on the reported biochemical interactions we developed a regulatory model for the core signalling factors IHH, PTCH1, and PTHrP and included two cell types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes. We show that the reported IHH-PTCH1 interaction gives rise to a Schnakenberg-type Turing kinetics, and that inclusion of PTHrP is important to achieve robust patterning when coupling patterning and tissue dynamics. The model reproduces relevant spatiotemporal gene expression patterns, as well as a number of relevant mutant phenotypes. In summary, we propose that a ligand-receptor based Turing mechanism may control the emergence of patterns during long bone development, with PTHrP as an important mediator to confer patterning robustness when the sensitive Turing system is coupled to the dynamics of a growing and differentiating tissue. We have previously shown that ligand-receptor based Turing mechanisms can also result from BMP-receptor, SHH-receptor, and GDNF-receptor interactions, and that these reproduce the wildtype and mutant patterns during digit formation in limbs and branching morphogenesis in lung and kidneys. Receptor-ligand interactions may thus constitute a general mechanism to generate Turing patterns in nature.

  2. The Development of the Calvarial Bones and Sutures and the Pathophysiology of Craniosynostosis.

    Science.gov (United States)

    Ishii, Mamoru; Sun, Jingjing; Ting, Man-Chun; Maxson, Robert E

    2015-01-01

    The skull vault is a complex, exquisitely patterned structure that plays a variety of key roles in vertebrate life, ranging from the acquisition of food to the support of the sense organs for hearing, smell, sight, and taste. During its development, it must meet the dual challenges of protecting the brain and accommodating its growth. The bones and sutures of the skull vault are derived from cranial neural crest and head mesoderm. The frontal and parietal bones develop from osteogenic rudiments in the supraorbital ridge. The coronal suture develops from a group of Shh-responsive cells in the head mesoderm that are collocated, with the osteogenic precursors, in the supraorbital ridge. The osteogenic rudiments and the prospective coronal suture expand apically by cell migration. A number of congenital disorders affect the skull vault. Prominent among these is craniosynostosis, the fusion of the bones at the sutures. Analysis of the pathophysiology underling craniosynostosis has identified a variety of cellular mechanisms, mediated by a range of signaling pathways and effector transcription factors. These cellular mechanisms include loss of boundary integrity, altered sutural cell specification in embryos, and loss of a suture stem cell population in adults. Future work making use of genome-wide transcriptomic approaches will address the deep structure of regulatory interactions and cellular processes that unify these seemingly diverse mechanisms.

  3. Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In Vitro and Accelerates Bone Development in Rats.

    Science.gov (United States)

    Clough, Bret H; Ylostalo, Joni; Browder, Elizabeth; McNeill, Eoin P; Bartosh, Thomas J; Rawls, H Ralph; Nakamoto, Tetsuo; Gregory, Carl A

    2017-03-01

    Theobromine (THB) is one of the major xanthine-like alkaloids found in cacao plant and a variety of other foodstuffs such as tea leaves, guarana and cola nuts. Historically, THB and its derivatives have been utilized to treat cardiac and circulatory disorders, drug-induced nephrotoxicity, proteinuria and as an immune-modulator. Our previous work demonstrated that THB has the capacity to improve the formation of hydroxyl-apatite during tooth development, suggesting that it may also enhance skeletal development. With its excellent safety profile and resistance to pharmacokinetic elimination, we reasoned that it might be an excellent natural osteoanabolic supplement during pregnancy, lactation and early postnatal growth. To determine whether THB had an effect on human osteoprogenitors, we subjected primary human bone marrow mesenchymal stem cells (hMSCs) to osteogenic assays after exposure to THB in vitro and observed that THB exposure increased the rate of osteogenesis and mineralization by hMSCs. Moreover, THB exposure resulted in a list of upregulated mRNA transcripts that best matched an osteogenic tissue expression signature as compared to other tissue expression signatures archived in several databases. To determine whether oral administration of THB resulted in improved skeletal growth, we provided pregnant rats with chow supplemented with THB during pregnancy and lactation. After weaning, offspring received THB continuously until postnatal day 50 (approximately 10 mg kg(-1) day(-1)). Administration of THB resulted in neonates with larger bones, and 50-day-old offspring accumulated greater body mass, longer and thicker femora and superior tibial trabecular parameters. The accelerated growth did not adversely affect the strength and resilience of the bones. These results indicate that THB increases the osteogenic potential of bone marrow osteoprogenitors, and dietary supplementation of a safe dose of THB to expectant mothers and during the postnatal period

  4. Development of biomimetic nanocomposites as bone extracellular matrix for human osteoblastic cells.

    Science.gov (United States)

    Bhowmick, Arundhati; Mitra, Tapas; Gnanamani, Arumugam; Das, Manas; Kundu, Patit Paban

    2016-05-05

    Here, we have developed biomimetic nanocomposites containing chitosan, poly(vinyl alcohol) and nano-hydroxyapatite-zinc oxide as bone extracellular matrix for human osteoblastic cells and characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction. Scanning electron microscopy images revealed interconnected macroporous structures. Moreover, in this study, the problem related to fabricating a porous composite with good mechanical strength has been resolved by incorporating 5wt% of nano-hydroxyapatite-zinc oxide into chitosan-poly(vinyl alcohol) matrix; the present composite showed high tensile strength (20.25MPa) while maintaining appreciable porosity (65.25%). These values are similar to human cancellous bone. These nanocomposites also showed superior water uptake, antimicrobial and biodegradable properties than the previously reported results. Compatibility with human blood and pH was observed, indicating nontoxicity of these materials to the human body. Moreover, proliferation of osteoblastic MG-63 cells onto the nanocomposites was also observed without having any negative effect.

  5. Genetically engineered mouse models to evaluate the role of Wnt secretion in bone development and homeostasis.

    Science.gov (United States)

    Williams, Bart O

    2016-03-01

    Alterations in components of the Wnt signaling pathway are associated with altered bone development and homeostasis in several human diseases. We created genetically engineered mouse models (GEMMs) that mimic the cellular defect associated with the Porcupine mutations in patients with Goltz Syndrome/Focal Dermal Hypoplasia. These GEMMs were established by utilizing mice containing a conditionally inactivatable allele of Wntless/GPR177 (a gene encoding a protein required for the transport of Porcupine-modified ligand to the plasma membrane for secretion). We crossed this strain to another which drives cre-mediated gene deletion in mature osteoblasts (Osteocalcin-cre) resulted in mice lacking the ability to secrete Wnt ligands in this cell type. These mice displayed severely reduced bone mass and provide a model to understand the effects of disrupting the ability to secrete Wnt ligands on the skeletal system.

  6. Bone mineral density of tibae and femura of broiler breeders: growth, development and production

    Directory of Open Access Journals (Sweden)

    ICL Almeida Paz

    2006-06-01

    Full Text Available The aim of this study was to follow-up the physiological variations in the development of the bone tissue, associating them with the egg production curve. This study was carried out in the facilities of the Faculdade de Medicina Veterinária e Zootecnia of the UNESP, Botucatu, Brazil. Twenty-three families of Ross broiler breeders were used, each family consisting of 13 females and 1 male, distributed in 23 pens of 5.0m² each. The management was that recommended by the genetic company manual (Agroceres Ross, 2003, with daily feeding until 6th week of age; and birds were fed according to a 5:2 schedule (5 days fed, 2 days of fasting between 7 and 17 weeks of age, returning to daily feeding starting at 18 weeks of age. Birds did not receive afternoon calcium supplementation. On the fourth week of rearing, 84 females were removed for bone analyses of the right tibia and femur, using optical densitometry in radiographic images technique. These analyses were sequentially carried out in 4, 8, 12, 15, 20, 24, 30, 35, 42, 47, and 52 week-old birds. The egg production curve of the birds was followed-up and associated to bone mineral density results. For bone mineral density evaluation (BMD birds were divided by weight categories as light, intermediate, or heavy within each data age. BMD values of the tibias were not influenced by weight range, but by the age at collection. On the other hand, interactions were found among femur BMD values and weight and age categories. There was no correlation between eggshell quality and femur BMD. A negative correlation (-0.15 was observed between tibia BMD and eggshell percentage. It was possible to conclude that the egg production has little influence on bone mineral density of the birds probably because there was no need of bone mineral mobilization during the production period, since the observed egg production was below that observed under commercial conditions.

  7. Development and testing of texture discriminators for the analysis of trabecular bone in proximal femur radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Huber, M. B.; Carballido-Gamio, J.; Fritscher, K.; Schubert, R.; Haenni, M.; Hengg, C.; Majumdar, S.; Link, T. M. [Department of Radiology and Biomedical Imaging, University of California, 400 Parnassus Avenue, San Francisco, California 94143 (United States); University of Health Sciences, Medical Informatics and Technology, 6060 Hall (Austria); AO Development Institute, 7270 Davos Platz (Switzerland); Medical University Innsbruck, 6020 Innsbruck (Austria); Department of Radiology and Biomedical Imaging, University of California, 400 Parnassus Avenue, San Francisco, California 94143 (United States)

    2009-11-15

    }=0.61 (MF and MG features, p<0.01) and were partially independent of BMD. The correlations were dependent on the choice of the ROI and the texture measure. The best predictive multiregression model for failure load R{sub adj}{sup 2}=0.86 (p<0.001) included a set of recently developed texture methods (MF and SIM) but excluded bone mineral density and commonly used texture measures. Conclusions: The results suggest that texture information contained in trabecular bone structure visualized on radiographs may predict whether an implant anchorage can be used and may determine the local bone quality from preoperative radiographs.

  8. Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

    Science.gov (United States)

    Ferreira, Diêgo dos Santos; Faria, Samilla Dornelas; Lopes, Sávia Caldeira de Araújo; Teixeira, Cláudia Salviano; Malachias, Angelo; Magalhães-Paniago, Rogério; de Souza Filho, José Dias; Oliveira, Bruno Luis de Jesus Pinto; Guimarães, Alexander Ramos; Caravan, Peter; Ferreira, Lucas Antônio Miranda; Alves, Ricardo José; Oliveira, Mônica Cristina

    2016-01-01

    Background Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges. Purpose To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases. Materials and methods Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals. Results Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart. Conclusion These results suggest that bone-targeted p

  9. Bone Morphogenetic Protein 4 Signalling in Neural Stem and Progenitor Cells during Development and after Injury

    Directory of Open Access Journals (Sweden)

    Alistair E. Cole

    2016-01-01

    Full Text Available Substantial progress has been made in identifying the extracellular signalling pathways that regulate neural stem and precursor cell biology in the central nervous system (CNS. The bone morphogenetic proteins (BMPs, in particular BMP4, are key players regulating neuronal and glial cell development from neural precursor cells in the embryonic, postnatal, and injured CNS. Here we review recent studies on BMP4 signalling in the generation of neurons, astrocytes, and oligodendroglial cells in the CNS. We also discuss putative mechanisms that BMP4 may utilise to influence glial cell development following CNS injury and highlight some questions for further research.

  10. Design and development of mesoporous glass-based biomaterials for bone tissue engineering and drug release systems

    OpenAIRE

    Philippart, Anahí

    2016-01-01

    In order to overcome clinical challenges for bone tissue regeneration, current tissue engineering research focuses on developing highly performant biomaterials in terms of multifunctionality, i.e. materials that are capable of stimulating bone regeneration and exhibit drug delivery capabilities as well as sufficient mechanical stability. In the framework of this research topic, the work here presented focuses on the development of multifunctional mesoporous bioactive glasses (mBGs) and on the...

  11. A review of the actual knowledge of the processes governing growth and development of long bones.

    Science.gov (United States)

    Pazzaglia, Ugo Ernesto; Beluffi, Giampiero; Benetti, Anna; Bondioni, Maria Pia; Zarattini, Guido

    2011-01-01

    Autoptic samples of human bones (from 8 weeks of gestation to 12 years of age) and a second group of serial, skeletal x-rays (required for pathologies not related to bone dysplasia in children from 4 months to 17 years of age) provided the material for the analysis of the physes normal growth mechanism presented in this review. Before the appearance of the ossification centers epiphyseal growth rests exclusively on chondrocytes proliferation (interstitial growth), without any detectable differentiated cellular organization. When endochondral ossification starts a defined spatial disposition of chondrocytes and a corresponding organization of the intercellular matrix is set up, so that it is possible to identify a growth vector corresponding to the columns of piled chondrocytes with direction from hypertrophic toward the proliferative cell layers. The complexity of the tubular bones growth process is well represented by the spatial arrangement of the growth vectors. In the late epiphyseal growth another mechanism is active in addition to endochondral ossification, namely, articular cartilage interstitial growth and subchondral remodelling. The knowledge of the normal mode of organization of the physis and its temporal sequence can help to better understand of the deviaton from the normal development of metaphyseal and epiphyseal dysplasias.

  12. Development of a nanofiltration method for bone collagen 14C AMS dating

    Science.gov (United States)

    Boudin, Mathieu; Boeckx, Pascal; Buekenhoudt, Anita; Vandenabeele, Peter; Van Strydonck, Mark

    2013-01-01

    Radiocarbon dating of bones is usually performed on the collagen fraction. However, this collagen can contain exogenous molecules, including humic substances (HSs) and/or other soil components that may have a different age than the bone. Incomplete removal can result in biased 14C dates. Ultrafiltration of collagen, dissolved as gelatin (molecular weight (MW) ∼100,000 Dalton), has received considerable attention to obtain more reliable dates. Ultrafiltration is an effective method of removal of low-molecular weight contaminants from bone collagen but it does not remove high-molecular weight contaminants, such as cross-linked humic collagen complexes. However, comparative dating studies have raised the question whether this cleaning step itself may introduce contamination with carbon from the filters used. In this study, a nanofiltration method was developed using a ceramic filter to avoid a possible extraneous carbon contamination introduced by the filter. This method should be applicable to various protein materials e.g. collagen, silk, wool, leather and should be able to remove low-molecular and high molecular weight HSs. In this study bone collagen was hot acid hydrolyzed to amino acids and nanofiltrated. A filter with a molecular weight cutoff (MWCO) of 450 Dalton was chosen in order to collect the amino acids in the permeate and the HSs in the retentate. Two pilot studies were set up. Two nanofiltration types were tested in pilot study 1: dead end and cross flow filtration. Humic substance (HS)-solutions with fossil carbon and modern hydrolyzed collagen contaminated with HSs were filtrated and analyzed with spectrofluorescence to determine the HS removal. Cross flow nanofiltration showed the most efficient HS removal. A second pilot study based upon these results was set up wherein only cross flow filtration was performed. 14C measurements of the permeates of hydrolyzed modern collagen contaminated with fossil HSs demonstrate a significant but incomplete

  13. Development of a nanofiltration method for bone collagen {sup 14}C AMS dating

    Energy Technology Data Exchange (ETDEWEB)

    Boudin, Mathieu, E-mail: mathieu.boudin@ugent.be [Royal Institute for Cultural Heritage, Jubelpark 1, B-1000 Brussels (Belgium); Ghent University, Faculty of Bioscience Engineering, Laboratory of Applied Physical Chemistry, Coupure Links 653, B-9000 Ghent (Belgium); Boeckx, Pascal [Ghent University, Faculty of Bioscience Engineering, Laboratory of Applied Physical Chemistry, Coupure Links 653, B-9000 Ghent (Belgium); Buekenhoudt, Anita [Flemish Institute for Technological Research, Separation and Conversion Technology, Boeretang 200, B-2400 Mol (Belgium); Vandenabeele, Peter [Ghent University, Department of Archaeology, Sint-Pietersnieuwstraat 35, B-9000 Ghent (Belgium); Van Strydonck, Mark [Royal Institute for Cultural Heritage, Jubelpark 1, B-1000 Brussels (Belgium)

    2013-01-15

    Radiocarbon dating of bones is usually performed on the collagen fraction. However, this collagen can contain exogenous molecules, including humic substances (HSs) and/or other soil components that may have a different age than the bone. Incomplete removal can result in biased {sup 14}C dates. Ultrafiltration of collagen, dissolved as gelatin (molecular weight (MW) {approx}100,000 Dalton), has received considerable attention to obtain more reliable dates. Ultrafiltration is an effective method of removal of low-molecular weight contaminants from bone collagen but it does not remove high-molecular weight contaminants, such as cross-linked humic collagen complexes. However, comparative dating studies have raised the question whether this cleaning step itself may introduce contamination with carbon from the filters used. In this study, a nanofiltration method was developed using a ceramic filter to avoid a possible extraneous carbon contamination introduced by the filter. This method should be applicable to various protein materials e.g. collagen, silk, wool, leather and should be able to remove low-molecular and high molecular weight HSs. In this study bone collagen was hot acid hydrolyzed to amino acids and nanofiltrated. A filter with a molecular weight cutoff (MWCO) of 450 Dalton was chosen in order to collect the amino acids in the permeate and the HSs in the retentate. Two pilot studies were set up. Two nanofiltration types were tested in pilot study 1: dead end and cross flow filtration. Humic substance (HS)-solutions with fossil carbon and modern hydrolyzed collagen contaminated with HSs were filtrated and analyzed with spectrofluorescence to determine the HS removal. Cross flow nanofiltration showed the most efficient HS removal. A second pilot study based upon these results was set up wherein only cross flow filtration was performed. {sup 14}C measurements of the permeates of hydrolyzed modern collagen contaminated with fossil HSs demonstrate a significant

  14. A Development of a Human Cranial Bone Surrogate for Impact Studies

    Directory of Open Access Journals (Sweden)

    Jack C Roberts

    2013-10-01

    Full Text Available In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the 3-layer (inner table-diplöe-outer table architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three layer surrogate cranial bone samples for three point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures seen in pendulum impacts of intact human skulls. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  15. Bone tumor

    Science.gov (United States)

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

  16. Novel biocompatible polymeric blends for bone regeneration: Material and matrix design and development

    Science.gov (United States)

    Deng, Meng

    The first part of the work presented in this dissertation is focused on the design and development of novel miscible and biocompatible polyphosphazene-polyester blends as candidate materials for scaffold-based bone tissue engineering applications. Biodegradable polyesters such as poly(lactide-co-glycolide) (PLAGA) are among the most widely used polymeric materials for bone tissue engineering. However, acidic degradation products resulting from the bulk degradation mechanism often lead to catastrophic failure of the structure integrity, and adversely affect biocompatibility both in vitro and in vivo. One promising approach to circumvent these limitations is to blend PLAGA with other macromolecules that can buffer the acidic degradation products with a controlled degradation rate. Biodegradable polyphosphazenes (PPHOS), a new class of biomedical materials, have proved to be superior candidate materials to achieve this objective due to their unique buffering degradation products. A highly practical blending approach was adopted to develop novel biocompatible, miscible blends of these two polymers. In order to achieve this miscibility, a series of amino acid ester, alkoxy, aryloxy, and dipeptide substituted PPHOS were synthesized to promote hydrogen bonding interactions with PLAGA. Five mixed-substituent PPHOS compositions were designed and blended with PLAGA at different weight ratios producing candidate blends via a mutual solvent method. Preliminary characterization identified two specific side groups namely glycylglycine dipeptide and phenylphenoxy that resulted in improved blend miscibility and enhanced in vitro osteocompatibility. These findings led to the synthesis of a mixed-substituent polyphosphazene poly[(glycine ethyl glycinato)1(phenylphenoxy)1phosphazene] (PNGEGPhPh) for blending with PLAGA. Two dipeptide-based blends having weight ratios of PNGEGPhPh to PLAGA namely 25:75 (Matrix1) and 50:50 (Matrix2) were fabricated. Both of the blends were

  17. Development of Collagen/Demineralized Bone Powder Scaffolds and Periosteum-Derived Cells for Bone Tissue Engineering Application

    Directory of Open Access Journals (Sweden)

    Wilairat Leeanansaksiri

    2013-01-01

    Full Text Available The aim of this study was to investigate physical and biological properties of collagen (COL and demineralized bone powder (DBP scaffolds for bone tissue engineering. DBP was prepared and divided into three groups, based on various particle sizes: 75–125 µm, 125–250 µm, and 250–500 µm. DBP was homogeneously mixed with type I collagen and three-dimensional scaffolds were constructed, applying chemical crosslinking and lyophilization. Upon culture with human periosteum-derived cells (PD cells, osteogenic differentiation of PD cells was investigated using alkaline phosphatase (ALP activity and calcium assay kits. The physical properties of the COL/DBP scaffolds were obviously different from COL scaffolds, irrespective of the size of DBP. In addition, PD cells cultured with COL scaffolds showed significantly higher cell adhesion and proliferation than those with COL/DBP scaffolds. In contrast, COL/DBP scaffolds exhibited greater osteoinductive potential than COL scaffolds. The PD cells with COL/DBP scaffolds possessed higher ALP activity than those with COL scaffolds. PD cells cultured with COL/DBP scaffolds with 250–500 mm particle size yielded the maximum calcium deposition. In conclusion, PD cells cultured on the scaffolds could exhibit osteoinductive potential. The composite scaffold of COL/DBP with 250–500 mm particle size could be considered a potential bone tissue engineering implant.

  18. Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone

    DEFF Research Database (Denmark)

    Galli, Giorgio Giacomo; Honnens de Lichtenberg, Kristian; Carrara, Matteo

    2012-01-01

    expressed in developing bones; and, by genome-wide mapping of Prdm5 occupancy in pre-osteoblastic cells, we uncover a novel and unique role for Prdm5 in targeting all mouse collagen genes as well as several SLRP proteoglycan genes. In particular, we show that Prdm5 controls both Collagen I transcription...... and fibrillogenesis by binding inside the Col1a1 gene body and maintaining RNA polymerase II occupancy. In vivo, Prdm5 loss results in delayed ossification involving a pronounced impairment in the assembly of fibrillar collagens. Collectively, our results define a novel role for Prdm5 in sustaining...

  19. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels.

    Science.gov (United States)

    Maes, Christa; Kobayashi, Tatsuya; Selig, Martin K; Torrekens, Sophie; Roth, Sanford I; Mackem, Susan; Carmeliet, Geert; Kronenberg, Henry M

    2010-08-17

    During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone. Throughout the translocation, some precursors were found to intimately associate with invading blood vessels, in pericyte-like fashion. A similar coinvasion occurs during endochondral healing of bone fractures. In contrast, perichondrial mature osteoblasts did not exhibit perivascular localization and remained in the outer cortex of developing bones. These findings reveal the specific involvement of immature osteoblast precursors in the coupled vascular and osteogenic transformation essential to endochondral bone development and repair.

  20. Development and Characterization of Novel Porous 3D Alginate-Cockle Shell Powder Nanobiocomposite Bone Scaffold

    Directory of Open Access Journals (Sweden)

    B. Hemabarathy Bharatham

    2014-01-01

    Full Text Available A novel porous three-dimensional bone scaffold was developed using a natural polymer (alginate/Alg in combination with a naturally obtained biomineral (nano cockle shell powder/nCP through lyophilization techniques. The scaffold was developed in varying composition mixture of Alg-nCP and characterized using various evaluation techniques as well as preliminary in vitro studies on MG63 human osteoblast cells. Morphological observations using SEM revealed variations in structures with the use of different Alg-nCP composition ratios. All the developed scaffolds showed a porous structure with pore sizes ideal for facilitating new bone growth; however, not all combination mixtures showed subsequent favorable characteristics to be used for biological applications. Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced significantly promising results in terms of mechanical strength, degradation rate, and increased cell proliferation rates making it potentially the optimum composition mixture of Alg-nCP with future application prospects.

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

    Science.gov (United States)

    DeWoody, Yssa

    1996-01-01

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

  2. Bone matrix calcification during embryonic and postembryonic rat calvarial development assessed by SEM-EDX spectroscopy, XRD, and FTIR spectroscopy.

    Science.gov (United States)

    Henmi, Akiko; Okata, Hiroshi; Anada, Takahisa; Yoshinari, Mariko; Mikami, Yasuto; Suzuki, Osamu; Sasano, Yasuyuki

    2016-01-01

    Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase in the Ca/P ratio is involved in maturation of the crystal is not known. The relationships among organic components and mineral changes are also unclear. The study was designed to investigate the process of calcification during rat calvarial bone development. Calcification was evaluated by analyzing the atomic distribution and concentration of Ca, P, and C with scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Histological analysis showed that rat calvarial bone formation started around embryonic day 16. The areas of Ca and P expanded, matching the region of the developing bone matrix, whereas the area of C became localized around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like structure of the minerals at embryonic day 16 gradually transformed into poorly crystalline hydroxyapatite, whereas the proportion of mineral to protein increased until postnatal week 6. FTIR analysis also showed that crystallization of hydroxyapatite started around embryonic day 20, by which time SEM-EDX spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios had decreased significantly. The study suggests that the Ca/P molar ratio increases and the proportion of organic components such as proteins of the bone matrix decreases during the early stage of calcification, whereas crystal maturation continues throughout embryonic and postembryonic bone development.

  3. Development of a novel method for surgical implant design optimization through noninvasive assessment of local bone properties.

    Science.gov (United States)

    Schiuma, D; Brianza, S; Tami, A E

    2011-03-01

    A method was developed to improve the design of locking implants by finding the optimal paths for the anchoring elements, based on a high resolution pQCT assessment of local bone mineral density (BMD) distribution and bone micro-architecture (BMA). The method consists of three steps: (1) partial fixation of the implant to the bone and creation of a reference system, (2) implant removal and pQCT scan of the bone, and (3) determination of BMD and BMA of all implant-anchoring locations along the actual and alternative directions. Using a PHILOS plate, the method uncertainty was tested on an artificial humerus bone model. A cadaveric humerus was used to quantify how the uncertainty of the method affects the assessment of bone parameters. BMD and BMA were determined along four possible alternative screw paths as possible criteria for implant optimization. The method is biased by a 0.87 ± 0.12 mm systematic uncertainty and by a 0.44 ± 0.09 mm random uncertainty in locating the virtual screw position. This study shows that this method can be used to find alternative directions for the anchoring elements, which may possess better bone properties. This modification will thus produce an optimized implant design.

  4. The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

    Science.gov (United States)

    Gervas-Arruga, Javier; Cebolla, Jorge Javier; de Blas, Ignacio; Roca, Mercedes; Pocovi, Miguel; Giraldo, Pilar

    2015-01-01

    data suggest that patients with GD1 have increased susceptibility to developing bone disease owing to the coexistence of genetic variants, and that genetic background in GD1 is fundamental to regulate the impact of proinflammatory status on the development of bone disease.

  5. The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

    Directory of Open Access Journals (Sweden)

    Javier Gervas-Arruga

    genotypes. The data suggest that patients with GD1 have increased susceptibility to developing bone disease owing to the coexistence of genetic variants, and that genetic background in GD1 is fundamental to regulate the impact of proinflammatory status on the development of bone disease.

  6. A Conditional Knockout Mouse Model Reveals a Critical Role of PKD1 in Osteoblast Differentiation and Bone Development

    Science.gov (United States)

    Li, Shao; Xu, Wanfu; Xing, Zhe; Qian, Jiabi; Chen, Liping; Gu, Ruonan; Guo, Wenjing; Lai, Xiaoju; Zhao, Wanlu; Li, Songyu; Wang, Yaodong; Wang, Q. Jane; Deng, Fan

    2017-01-01

    The protein kinase D family of serine/threonine kinases, particularly PKD1, has been implicated in the regulation of a complex array of fundamental biological processes. However, its function and mechanism underlying PKD1-mediated the bone development and osteoblast differentiation are not fully understood. Here we demonstrate that loss of PKD1 function led to impaired bone development and osteoblast differentiation through STAT3 and p38 MAPK signaling using in vitro and in vivo bone-specific conditional PKD1-knockout (PKD1-KO) mice models. These mice developed markedly craniofacial dysplasia, scapula dysplasia, long bone length shortage and body weight decrease compared with wild-type littermates. Moreover, deletion of PKD1 in vivo reduced trabecular development and activity of osteoblast development, confirmed by Micro-CT and histological staining as well as expression of osteoblastic marker (OPN, Runx2 and OSX). Mechanistically, loss of PKD1 mediated the downregulation of osteoblast markers and impaired osteoblast differentiation through STAT3 and p38 MAPK signaling pathways. Taken together, these results demonstrated that PKD1 contributes to the osteoblast differentiation and bone development via elevation of osteoblast markers through activation of STAT3 and p38 MAPK signaling pathways. PMID:28084409

  7. Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

    Directory of Open Access Journals (Sweden)

    Ferreira DS

    2016-08-01

    Full Text Available Diêgo dos Santos Ferreira,1,2 Samilla Dornelas Faria,1 Sávia Caldeira de Araújo Lopes,1 Cláudia Salviano Teixeira,1 Angelo Malachias,3 Rogério Magalhães-Paniago,3 José Dias de Souza Filho,4 Bruno Luis de Jesus Pinto Oliveira,2 Alexander Ramos Guimarães,2 Peter Caravan,2 Lucas Antônio Miranda Ferreira,1 Ricardo José Alves,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy,Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Department of Physics, 4Department of Chemistry, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.Purpose: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX in an acidic environment for future application as a tool for treatment of bone metastases.Materials and methods: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5, plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was

  8. Development of a strain rate dependent material model of human cortical bone for computer-aided reconstruction of injury mechanisms.

    Science.gov (United States)

    Asgharpour, Zahra; Zioupos, Peter; Graw, Matthias; Peldschus, Steffen

    2014-03-01

    Computer-aided methods such as finite-element simulation offer a great potential in the forensic reconstruction of injury mechanisms. Numerous studies have been performed on understanding and analysing the mechanical properties of bone and the mechanism of its fracture. Determination of the mechanical properties of bones is made on the same basis used for other structural materials. The mechanical behaviour of bones is affected by the mechanical properties of the bone material, the geometry, the loading direction and mode and of course the loading rate. Strain rate dependency of mechanical properties of cortical bone has been well demonstrated in literature studies, but as many of these were performed on animal bones and at non-physiological strain rates it is questionable how these will apply in the human situations. High strain-rates dominate in a lot of forensic applications in automotive crashes and assault scenarios. There is an overwhelming need to a model which can describe the complex behaviour of bone at lower strain rates as well as higher ones. Some attempts have been made to model the viscoelastic and viscoplastic properties of the bone at high strain rates using constitutive mathematical models with little demonstrated success. The main objective of the present study is to model the rate dependent behaviour of the bones based on experimental data. An isotropic material model of human cortical bone with strain rate dependency effects is implemented using the LS-DYNA material library. We employed a human finite element model called THUMS (Total Human Model for Safety), developed by Toyota R&D Labs and the Wayne State University, USA. The finite element model of the human femur is extracted from the THUMS model. Different methods have been employed to develop a strain rate dependent material model for the femur bone. Results of one the recent experimental studies on human femur have been employed to obtain the numerical model for cortical femur. A

  9. Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

    Science.gov (United States)

    Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

    2009-04-01

    The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

  10. Development and characterization of novel alginate-based hydrogels as vehicles for bone substitutes.

    Science.gov (United States)

    Morais, D S; Rodrigues, M A; Silva, T I; Lopes, M A; Santos, M; Santos, J D; Botelho, C M

    2013-06-05

    In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HAP. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca(2+) ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 h at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HAP, particularly the hydrogel Alg/HA.

  11. Development and biological evaluation of {sup 90}Y-BPAMD as a novel bone seeking therapeutic agent

    Energy Technology Data Exchange (ETDEWEB)

    Rabiei, Ali; Shamsaei, Mojtaba [Amir Kabir University of Technology, Tehran (Iran, Islamic Republic of). Energy Engineering and Physics Dept.; Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Enayati, Razieh [Islamic Azad Univ. (IAU), Tehran (Iran, Islamic Republic of). Faculty of Engineering

    2016-07-01

    Nowadays, the bone-seeking radiopharmaceuticals play an important role in the treatment of the bone-related pathologies. Whereas various phosphonate ligands have already been identified, a DOTA-based bisphosphonate, 4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) -1,4,7,10-tetraazacyclododec-1-yl (BPAMD) with better characteristics has recently been synthesized. In this study, {sup 90}Y-BPAMD was developed with radiochemical purity >98% and the specific activity of 3.52 TBq/mmol in the optimized conditions as a new bone-seeking therapeutic agent. The complex demonstrated significant stability at room temperature and in human serum even after 48 h. At even low amount of hydroxyapatite (5 mg), more than 90% binding to hydroxyapatite was observed. Biodistribution studies after injection of the complex into the Syrian rats showed major accumulation of the labelled compound in the bone tissue and an insignificant uptake in the other organs all the times after injection. Generally, {sup 90}Y-BPAMD demonstrated interesting characteristics compared to the other {sup 90}Y bone-seeking agents and even {sup 166}Ho-BPAMD, and can be considered as a new bone-seeking candidate for therapeutic applications.

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

    Science.gov (United States)

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

    2015-04-15

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

  13. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations.

    Science.gov (United States)

    Weaver, C M; Gordon, C M; Janz, K F; Kalkwarf, H J; Lappe, J M; Lewis, R; O'Karma, M; Wallace, T C; Zemel, B S

    2016-04-01

    Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge

  14. The Effects of Elk Velvet Antler Dietary Supplementation on Physical Growth and Bone Development in Growing Rats.

    Science.gov (United States)

    Chen, Jiongran; Yang, Yanfei; Abbasi, Sepideh; Hajinezhad, Daryoush; Kontulainen, Saija; Honaramooz, Ali

    2015-01-01

    Elk velvet antler (EVA) has been used in traditional Oriental medicine for centuries to promote general health; however, little evidence for its effect on bone development is available. We investigated the effects of lifelong exposure of Wistar rats to a diet containing 10% EVA on physical growth and bone development. Measurements included weekly body weights, blood chemistry and kidney and testis/ovary indices (sacrificed at 5, 9, or 16 weeks of age), and bone traits of the femur bones by peripheral quantitative computed tomography (pQCT). Mean body weights were higher in the EVA group at 4-8 weeks in males and at 5 weeks of age in females. The kidney indices were greater in EVA dietary supplemented male rats at 5 and 16 weeks of age, in females at 16 weeks of age, and testis/ovary indices at 5 weeks of age. The femoral length was increased in both males and females at 5 weeks, and several pQCT-measured parameters had increased in EVA males and females. The activity of alkaline phosphatase (ALP) increased in EVA group while the content of calcium and phosphorus did not differ among groups. Our results seem to support a role for dietary supplementation of EVA on growth and bone development in this model.

  15. The Effects of Elk Velvet Antler Dietary Supplementation on Physical Growth and Bone Development in Growing Rats

    Directory of Open Access Journals (Sweden)

    Jiongran Chen

    2015-01-01

    Full Text Available Elk velvet antler (EVA has been used in traditional Oriental medicine for centuries to promote general health; however, little evidence for its effect on bone development is available. We investigated the effects of lifelong exposure of Wistar rats to a diet containing 10% EVA on physical growth and bone development. Measurements included weekly body weights, blood chemistry and kidney and testis/ovary indices (sacrificed at 5, 9, or 16 weeks of age, and bone traits of the femur bones by peripheral quantitative computed tomography (pQCT. Mean body weights were higher in the EVA group at 4–8 weeks in males and at 5 weeks of age in females. The kidney indices were greater in EVA dietary supplemented male rats at 5 and 16 weeks of age, in females at 16 weeks of age, and testis/ovary indices at 5 weeks of age. The femoral length was increased in both males and females at 5 weeks, and several pQCT-measured parameters had increased in EVA males and females. The activity of alkaline phosphatase (ALP increased in EVA group while the content of calcium and phosphorus did not differ among groups. Our results seem to support a role for dietary supplementation of EVA on growth and bone development in this model.

  16. Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration.

    Science.gov (United States)

    Maruyama, Takamitsu; Jeong, Jaeim; Sheu, Tzong-Jen; Hsu, Wei

    2016-02-01

    The suture mesenchyme serves as a growth centre for calvarial morphogenesis and has been postulated to act as the niche for skeletal stem cells. Aberrant gene regulation causes suture dysmorphogenesis resulting in craniosynostosis, one of the most common craniofacial deformities. Owing to various limitations, especially the lack of suture stem cell isolation, reconstruction of large craniofacial bone defects remains highly challenging. Here we provide the first evidence for an Axin2-expressing stem cell population with long-term self-renewing, clonal expanding and differentiating abilities during calvarial development and homeostastic maintenance. These cells, which reside in the suture midline, contribute directly to injury repair and skeletal regeneration in a cell autonomous fashion. Our findings demonstrate their true identity as skeletal stem cells with innate capacities to replace the damaged skeleton in cell-based therapy, and permit further elucidation of the stem cell-mediated craniofacial skeletogenesis, leading to revealing the complex nature of congenital disease and regenerative medicine.

  17. Bone marrow transplantation in patients with storage diseases: a developing country experience

    Directory of Open Access Journals (Sweden)

    Lange Marcos C.

    2006-01-01

    Full Text Available Bone marrow transplantation (BMT is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old were submitted to this procedure in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2, one had adrenoleukodystrophy (ALD and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient, one patient had no disease progression (ALD and in one patient this procedure did not change the natural course of the disease (MPS III.

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

    Science.gov (United States)

    Wada, Hironori; Iwasaki, Miki; Kawakami, Koichi

    2014-08-01

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

  19. The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development.

    Science.gov (United States)

    Estevez, M; Attisano, L; Wrana, J L; Albert, P S; Massagué, J; Riddle, D L

    1993-10-14

    The bone morphogenetic protein (BMP) family is a conserved group of signalling molecules within the transforming growth factor-beta (TGF-beta) superfamily. This group, including the Drosophila decapentaplegic (dpp) protein and the mammalian BMPs, mediates cellular interactions and tissue differentiation during development. Here we show that a homologue of human BMPs controls a developmental switch in the life cycle of the free-living soil nematode Caenorhabditis elegans. Starvation and overcrowding induce C. elegans to form a developmentally arrested, third-stage dauer larva. The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases. When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4. The daf-4 receptor is the first to be identified for any growth factor in the BMP family.

  20. Development of Magnesium and Siloxane-containing Vaterite and its Composite Materials for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Shinya eYamada

    2015-12-01

    Full Text Available Development of novel biomaterials with Mg2+, Ca2+ and silicate ions releasability for bone regeneration is now in progress. Several inorganic ions have been reported to stimulate bone-forming cells. We featured Ca2+, silicate and especially Mg2+ ions as growth factors for osteoblasts. Various biomaterials, such as ceramic powders and organic-inorganic composites, releasing the ions have been developed and investigated in their cytocompatibilities in our previous work. Through the investigation, providing the three ions was found to be effective to activate osteogenic cells. Mg and siloxane-containing vaterite (MgSiV was prepared by a carbonation process as an inorganic particles, which can provide simultaneously releasing ability of Ca2+, silicate and Mg2+ ions to biodegradable polymers. Poly(L-lactic acid (PLLA- and bioactive PLLA-based composites containing vaterite coatings were discussed on their degradability and cytocompatibility using a metallic Mg substrate as Mg2+ ion source. PLLA/SiV composite film, which has a releasability of silicate ions besides Ca2+ ion, was coated on a pure Mg substrate to be compared with the PLLA/V coating. The degradability and releasability of inorganic ions were morphologically and quantitatively monitored in a cell culture medium. The bonding strength between the coatings and Mg substrates was one of the key factors to control Mg2+ ion release from the substrates. The cell culture tests were conducted using mouse osteoblast-like cells (MC3T3-E1 cells; cellular morphology, proliferation and differentiation on the materials were evaluated. The PLLA/V and PLLA/SiV coatings on Mg substrates were found to enhance the proliferation; especially the PLLA/SiV coating possessed a higher ability of inducing the osteogenic differentiation of the cells.

  1. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells.

    Science.gov (United States)

    Hutton, Daphne L; Moore, Erika M; Gimble, Jeffrey M; Grayson, Warren L

    2013-09-01

    Vasculature is essential to the functional integration of a tissue-engineered bone graft to enable sufficient nutrient delivery and viability after implantation. Native bone and vasculature develop through intimately coupled, tightly regulated spatiotemporal cell-cell signaling. The complexity of these developmental processes has been a challenge for tissue engineers to recapitulate, resulting in poor codevelopment of both bone and vasculature within a unified graft. To address this, we cultured adipose-derived stromal/stem cells (ASCs), a clinically relevant, single cell source that has been previously investigated for its ability to give rise to vascularized bone grafts, and studied the effects of initial spatial organization of cells, the temporal addition of growth factors, and the presence of exogenous platelet-derived growth factor-BB (PDGF-BB) on the codevelopment of bone and vascular tissue structures. Human ASCs were aggregated into multicellular spheroids via the hanging drop method before encapsulation and subsequent outgrowth in fibrin gels. Cellular aggregation substantially increased vascular network density, interconnectivity, and pericyte coverage compared to monodispersed cultures. To form robust vessel networks, it was essential to culture ASCs in a purely vasculogenic medium for at least 8 days before the addition of osteogenic cues. Physiologically relevant concentrations of exogenous PDGF-BB (20 ng/mL) substantially enhanced both vascular network stability and osteogenic differentiation. Comparisons with the bone morphogenetic protein-2, another pro-osteogenic and proangiogenic growth factor, indicated that this potential to couple the formation of both lineages might be unique to PDGF-BB. Furthermore, the resulting tissue structure demonstrated the close association of mineral deposits with pre-existing vascular structures that have been described for developing tissues. This combination of a single cell source with a potent induction factor

  2. Total body bone development during early childhood in very low birth weight infants without cerebral palsy and mental retardation.

    Science.gov (United States)

    Osamura, T; Hasegawa, K; Yoshioka, H; Mizuta, R; Sawada, T

    1998-04-01

    Total body bone mineral density was measured by dual energy X-ray absorptiometry in 52 children who were very low birth weight (VLBW) infants without cerebral palsy and mental retardation (postconceptional age, from 10 mo to 6 y and 6 mo). VLBW infants in this study seemed to show compensatory acceleration of total body bone development, catching up with the control group during early childhood. However, in VLBW infants with at least one of the three factors such as total parenteral nutrition for 1 week or more, assisted ventilation for 1 week or more, or oxygen therapy for 28 d or more in their early stage after birth, adequate mineral supplementation might be especially important for long-term bone development.

  3. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents.

  4. 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.

  5. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

    Directory of Open Access Journals (Sweden)

    Takashi Watanabe

    Full Text Available Mastermind-like 1 (MAML1 is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2 from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/- embryos at embryonic day 16.5 (E16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1 and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1 expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1(-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

  6. Final Report for completed IPP Project:"Development of Plasma Ablation for Soft Tissue and Bone Surgery"

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Ian

    2009-09-01

    ArthroCare is a medical device company that develops, manufactures, and markets an advanced surgical tool, a plasma electro-surgical system for cutting and removing tissue. The hand-held electrical discharge device produces plasma in a biocompatible conductive fluid and tissue to which it is applied during surgery. Its products allow surgeons to operate with increased precision and accuracy, limiting damage to surrounding tissue thereby reducing pain and speeding recovery for the patient. In the past, the design of ArthfoCare's plasma wands has been an empirical undertaking. One goal of this R&D program was to put the phenomena involved on a sound scientific footing, allowing optimization of existing plasma based electro-surgery system technology, and the design and manufacture of new and improved kinds of scalpels, in particular for the surgical cutting of bone. Another important related goal of the program was to develop, through an experimental approach, new plasma wand approaches to the cutting ('shaving') of hard bone tissue. The goals of the CRADA were accomplished - computer models were used to predict important parameters of the plasma discharge and the bone environment, and several different approaches to bone-shaving were developed and demonstrated. The primary goal of the project was to develop and demonstrate an atmospheric-pressure plasma tool that is suitable for surgical use for shaving bone in humans. This goal was accomplished, in fact with several different alternative plasma approaches. High bone ablation speeds were measured. The use of probes ('plasma wand' - the surgical tool) with moving active electrodes was also explored, and there are advantages to this method. Another important feature is that the newly-exposed bone surface have only a very thin necrosis layer; this feature was demonstrated. This CRADA has greatly advanced our understanding of bone removal by atmospheric pressure plasmas in liquid, and puts Arthro

  7. Carpal and tarsal bone development is highly sensitive to three antiproliferative teratogens in mice.

    Science.gov (United States)

    Rahman, M E; Ishikawa, H; Watanabe, Y; Endo, A

    1996-01-01

    When pregnant mice were given small doses of teratogens (cytosine arabinoside, mitomycin C, or busulfan) that did not induce anomalies of any other organs, a high incidence of carpal and tarsal bone anomalies still occurred. The carpal and tarsal bones may be used as a sensitive target for teratogenicity testing.

  8. Cortical bone development under the growth plate is regulated by mechanical load transfer.

    NARCIS (Netherlands)

    Tanck, E.J.M.; Hannink, G.J.; Ruimerman, R.; Buma, P.; Burger, E.H.; Huiskes, R.

    2006-01-01

    Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections. We hypothesize that the developm

  9. Parallels between Nutrition and Physical Activity: Research Questions in Development of Peak Bone Mass

    Science.gov (United States)

    Weaver, Connie M.

    2015-01-01

    Lifestyle choices are attributed to 40% to 60% of adult peak bone mass. The National Osteoporosis Foundation (NOF) sought to update its 2000 consensus statement on peak bone mass and partnered with the American Society for Nutrition, which, in turn, charged a 9-member writing committee with using a systematic review approach to update the previous…

  10. Identification of MicroRNA for Intermuscular Bone Development in Blunt Snout Bream (Megalobrama amblycephala

    Directory of Open Access Journals (Sweden)

    Shi-Ming Wan

    2015-05-01

    Full Text Available Intermuscular bone (IB, which occurs only in the myosepta of the lower teleosts, is attracting more attention of researchers due to its particular development and lack of genetic information. MicroRNAs (miRNAs are emerging as important regulators for biological processes. In the present study, miRNAs from IBs and connective tissue (CT; encircled IBs from six-month-old Megalobrama amblycephala were characterized and compared. The results revealed the sequences and expression levels of 218 known miRNA genes (belonging to 97 families. Of these miRNAs, 44 known microRNA sequences exhibited significant expression differences between the two libraries, with 24 and 20 differentially-expressed miRNAs exhibiting higher expression in the CT and IBs libraries, respectively. The expressions of 11 miRNAs were selected to validate in nine tissues. Among the high-ranked predicted gene targets, differentiation, cell cycle, metabolism, signal transduction and transcriptional regulation were implicated. The pathway analysis of differentially-expressed miRNAs indicated that they were abundantly involved in regulating the development and differentiation of IBs and CT. This study characterized the miRNA for IBs of teleosts for the first time, which provides an opportunity for further understanding of miRNA function in the regulation of IB development.

  11. Bone Biopsy

    Science.gov (United States)

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

  12. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    Science.gov (United States)

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

  13. A "Do-It-Yourself" Interactive Bone Structure Module: Development and Evaluation of an Online Teaching Resource

    Science.gov (United States)

    Rich, Peter; Guy, Richard

    2013-01-01

    A stand-alone online teaching module was developed to cover an area of musculoskeletal anatomy (structure of bone) found to be difficult by students. The material presented in the module was not formally presented in any other way, thus providing additional time for other curriculum components, but it was assessed in the final examination. The…

  14. [Development and preclinical studies of insulating membranes based on poly-3-hydroxybutyrate-co-3-hydroxyvalerate for guided bone regeneration].

    Science.gov (United States)

    Ivanov, S Yu; Bonartsev, A P; Gazhva, Yu V; Zharkova, I I; Mukhametshin, R F; Mahina, T K; Myshkina, V L; Bonartseva, G A; Voinova, V V; Andreeva, N V; Akulina, E A; Kharitonova, E S; Shaitan, K V; Muraev, A A

    2015-01-01

    Bone tissue damages are one of the dominant causes of temporary disability and developmental disability. Currently, there are some methods of guided bone regeneration employing different osteoplastic materials and insulation membranes used in surgery. In this study, we have developed a method of preparation of porous membranes from the biopolymer poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV), produced by a strain of Azotobacter chroococcum 7B. The biocompatibility of the porous membranes was investigated in vitro using mesenchymal stem cells (MSCs) and in vivo on laboratory animals. The cytotoxicity test showed the possibility of cell attachment on membrane and histological studies confirmed good insulating properties the material. The data obtained demonstrate the high biocompatibility and the potential application of insulating membranes based on PHBV in bone tissue engineering.

  15. Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standardizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

    Science.gov (United States)

    2011-08-01

    Gamie Z, et al. 2008. The effect of beta-blockers on bone metabolism as potential drugs under investigation for osteoporosis and fracture healing. Expert...incadronate) on fracture healing of long bones in rats. J Bone Miner Res 14:969–979. 43. Cao Y, Mori S, Mashiba T, et al. 2002. Raloxifene, estrogen

  16. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  17. In vivo tungsten exposure alters B-cell development and increases DNA damage in murine bone marrow.

    Science.gov (United States)

    Kelly, Alexander D R; Lemaire, Maryse; Young, Yoon Kow; Eustache, Jules H; Guilbert, Cynthia; Molina, Manuel Flores; Mann, Koren K

    2013-02-01

    High environmental tungsten levels were identified near the site of a childhood pre-B acute lymphoblastic leukemia cluster; however, a causal link between tungsten and leukemogenesis has not been established. The major site of tungsten deposition is bone, the site of B-cell development. In addition, our in vitro data suggest that developing B lymphocytes are susceptible to tungsten-induced DNA damage and growth inhibition. To extend these results, we assessed whether tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild-type mice were exposed to tungsten in their drinking water for up to 16 weeks. Tungsten concentration in bone was analyzed by inductively coupled plasma mass spectrometry and correlated with B-cell development and DNA damage within the bone marrow. Tungsten exposure resulted in a rapid deposition within the bone following 1 week, and tungsten continued to accumulate thereafter albeit at a decreased rate. Flow cytometric analyses revealed a transient increase in mature IgD(+) B cells in the first 8 weeks of treatment, in animals of the highest and intermediate exposure groups. Following 16 weeks of exposure, all tungsten groups had a significantly greater percentage of cells in the late pro-/large pre-B developmental stages. DNA damage was increased in both whole marrow and isolated B cells, most notably at the lowest tungsten concentration tested. These findings confirm an immunological effect of tungsten exposure and suggest that tungsten could act as a tumor promoter, providing leukemic "hits" in multiple forms to developing B lymphocytes within the bone marrow.

  18. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

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

  19. Development and Testing of X-Ray Imaging-Enhanced Poly-L-Lactide Bone Screws.

    Directory of Open Access Journals (Sweden)

    Wei-Jen Chang

    Full Text Available Nanosized iron oxide particles exhibit osteogenic and radiopaque properties. Thus, iron oxide (Fe3O4 nanoparticles were incorporated into a biodegradable polymer (poly-L-lactic acid, PLLA to fabricate a composite bone screw. This multifunctional, 3D printable bone screw was detectable on X-ray examination. In this study, mechanical tests including three-point bending and ultimate tensile strength were conducted to evaluate the optimal ratio of iron oxide nanoparticles in the PLLA composite. Both injection molding and 3D printing techniques were used to fabricate the PLLA bone screws with and without the iron oxide nanoparticles. The fabricated screws were implanted into the femoral condyles of New Zealand White rabbits. Bone blocks containing the PLLA screws were resected 2 and 4 weeks after surgery. Histologic examination of the surrounding bone and the radiopacity of the iron-oxide-containing PLLA screws were evaluated. Our results indicated that addition of iron oxide nanoparticles at 30% significantly decreased the ultimate tensile stress properties of the PLLA screws. The screws with 20% iron oxide exhibited strong radiopacity compared to the screws fabricated without the iron oxide nanoparticles. Four weeks after surgery, the average bone volume of the iron oxide PLLA composite screws was significantly greater than that of PLLA screws without iron oxide. These findings suggested that biodegradable and X-ray detectable PLLA bone screws can be produced by incorporation of 20% iron oxide nanoparticles. Furthermore, these screws had significantly greater osteogenic capability than the PLLA screws without iron oxide.

  20. Uranium deposition in bones of Wistar rats associated with skeleton development.

    Science.gov (United States)

    Rodrigues, G; Arruda-Neto, J D T; Pereira, R M R; Kleeb, S R; Geraldo, L P; Primi, M C; Takayama, L; Rodrigues, T E; Cavalcante, G T; Genofre, G C; Semmler, R; Nogueira, G P; Fontes, E M

    2013-12-01

    Sixty female Wistar rats were submitted to a daily intake of ration doped with uranium from weaning to adulthood. Uranium in bone was quantified by the SSNTD (solid state nuclear track detection) technique, and bone mineral density (BMD) analysis performed. Uranium concentration as a function of age exhibited a sharp rise during the first week of the experiment and a drastic drop of 70% in the following weeks. Data interpretation indicates that uranium mimics calcium. Results from BMD suggest that radiation emitted by the incorporated Uranium could induce death of bone cells.

  1. What Is Bone Cancer?

    Science.gov (United States)

    ... start in bone, muscle, fibrous tissue, blood vessels, fat tissue, as well as some other tissues. They can develop anywhere in the body. There are several different types of bone tumors. Their names are based on ...

  2. What causes bone loss?

    Science.gov (United States)

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

  3. Postnatal development in Andersen's leaf-nosed bat Hipposideros pomona: flight, wing shape, and wing bone lengths.

    Science.gov (United States)

    Lin, Ai-Qing; Jin, Long-Ru; Shi, Li-Min; Sun, Ke-Ping; Berquist, Sean W; Liu, Ying; Feng, Jiang

    2011-04-01

    Postnatal changes in flight development, wing shape and wing bone lengths of 56 marked neonate Hipposideros pomona were investigated under natural conditions in southwest China. Flight experiments showed that pups began to flutter with a short horizontal displacement at 10 days and first took flight at 19 days, with most achieving sustained flight at 1 month old. Analysis of covariance on wingspan, wing area, and the other seven wing characteristics between 'pre-flight' and 'post-volancy' periods supports the hypothesis that growth had one 'pre-flight' trajectory and a different 'post-volancy' trajectory in bats. Wingspan, handwing length and area, armwing length and area, and total wing area increased linearly until the age of first flight, after which the growth rates decreased (all P Wing loading declined linearly until day 19 before ultimately decreasing to adult levels (P span-wise length and chord-wise length was evaluated to test the hypothesis that compensatory growth of wing bones in H. pomona occurred in both 'pre-flight' and 'post-volancy' periods. The frequency of short-long and long-short pairs was significantly greater than that of short-short, long-long pairs in most pairs of bone elements in adults. The results indicate that a bone 'shorter than expected' would be compensated by a bone or bones 'longer than expected', suggesting compensatory growth in H. pomona. The pairwise comparisons conducted in adults were also performed in young bats during 'pre-flight' and 'post-volancy' periods, demonstrating that compensatory growth occurred throughout postnatal ontogeny.

  4. Development of the software tool for generation and visualization of the finite element head model with bone conduction sounds

    Science.gov (United States)

    Nikolić, Dalibor; Milošević, Žarko; Saveljić, Igor; Filipović, Nenad

    2015-12-01

    Vibration of the skull causes a hearing sensation. We call it Bone Conduction (BC) sound. There are several investigations about transmission properties of bone conducted sound. The aim of this study was to develop a software tool for easy generation of the finite element (FE) model of the human head with different materials based on human head anatomy and to calculate sound conduction through the head. Developed software tool generates a model in a few steps. The first step is to do segmentation of CT medical images (DICOM) and to generate a surface mesh files (STL). Each STL file presents a different layer of human head with different material properties (brain, CSF, different layers of the skull bone, skin, etc.). The next steps are to make tetrahedral mesh from obtained STL files, to define FE model boundary conditions and to solve FE equations. This tool uses PAK solver, which is the open source software implemented in SIFEM FP7 project, for calculations of the head vibration. Purpose of this tool is to show impact of the bone conduction sound of the head on the hearing system and to estimate matching of obtained results with experimental measurements.

  5. Mineralization of Synthetic Polymer Scaffolds: A Bottom-upApproach for the Development of Artificial Bone

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jie; Viengkham, Malathong; Bertozzi, Carolyn R.

    2004-09-27

    The controlled integration of organic and inorganic components confers natural bone with superior mechanical properties. Bone biogenesis is thought to occur by templated mineralization of hard apatite crystals by an elastic protein scaffold, a process we sought to emulate with synthetic biomimetic hydrogel polymers. Crosslinked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. Strong adhesion between the organic and inorganic materials was achieved for hydrogels functionalized with either carboxylate or hydroxy ligands. The mineral-nucleating potential of hydroxyl groups identified here broadens the design parameters for synthetic bone-like composites and suggests a potential role for hydroxylated collagen proteins in bone mineralization.

  6. Development of the subchondral bone layer of the medial coronoid process of the canine ulna.

    Science.gov (United States)

    Wolschrijn, Claudia F; Weijs, Wim A

    2005-05-01

    The medial coronoid process (MCP) of the ulna takes part in the weight-bearing function of the elbow in quadrupedal animals. In this study, the timing of development of a solid subchondral bone layer (SBL) of the MCP in the dog is investigated, as this might be important in the pathogenesis of the fractured medial coronoid process, a common disease in young dogs of larger breeds. The SBL is considered to make an important contribution to the strength of the MCP. In this study, the SBL is visualized at the humeral articular side (H-side) and in the radial notch (RN) via three-dimensional reconstructions of micro-CT scans (34 mum voxel size) in nine young golden retrievers. After micro-CT scanning, the area was investigated histologically. Gradually, the appearance of the SBL on the H-side changes from a trabecular aspect to an even surface with gaps and finally to a completely even surface. The surface in the RN is still rough at 24 weeks after birth, although some consolidation has occurred. Initially, the enchondral ossification activity, as observed in the histological sections, is high, but later, when the intertrabecular spaces are filled in with calcified cartilage and bone, activity is less evident. Some vessels penetrated the SBL, but it is unclear if they account for all the gaps in the surface seen in micro-CT. In addition, the formation of a cortical structure of the proximal ulnar shaft could be visualized. The bony cortex is already even at the mediocaudal side of the proximal ulna 4 weeks after birth, but remains trabecular at the dorsal side until 6 weeks later. We hypothesize that the observed differences in the formation of an even SBL or cortex can be explained by mechanical factors. A smooth cortical layer has an even thickness and will be stronger than a cortex with varying thickness. In the MCP, compressive forces exerted by the humerus may be responsible for the early smoothening on the H-side. In the proximal ulna, the resistance to bending in

  7. Development of Novel Biocomposite Scaffold of Chitosan-Gelatin/Nanohydroxyapatite for Potential Bone Tissue Engineering Applications

    Science.gov (United States)

    Dan, Yang; Liu, Ouyang; Liu, Yong; Zhang, Yuan-Yuan; Li, Shuai; Feng, Xiao-bo; Shao, Zeng-wu; Yang, Cao; Yang, Shu-Hua; Hong, Ji-bo

    2016-11-01

    In this study, a three-dimensional chitosan-gelatin/nanohydroxyapatite (ChG/nHaP) scaffold was successfully fabricated and characterized in terms of swelling, degradation, cell proliferation, cell attachment, and mineralization characterizations. The ChG/nHaP scaffold was fabricated with a mean pore size of 100-180 μm. Our results showed that the physicochemical and biological properties of the scaffolds were affected by the presence of HaP. The swelling and degradation characteristics of the ChG scaffold were remarkably decreased by the addition of HaP. On the other hand, the presence of HaP remarkably improved the MC3T3-E1 cell attachment and cell growth in the scaffold membrane. The biocompatible nature of the ChG/nHaP scaffold leads to the development of finely scaled mineral deposits on the scaffold membrane. Thus, HaP played an important role in improving the biological performance of the scaffold. Therefore, the ChG/nHaP scaffold could be applied as a suitable material for bone tissue engineering applications.

  8. Development of Composite Poly(Lactide-co-Glycolide)- Nanodiamond Scaffolds for Bone Cell Growth.

    Science.gov (United States)

    Brady, Mariea A; Renzing, Andrea; Douglas, Timothy E L; Liu, Qin; Wille, Sebastian; Parizek, Martin; Bacakova, Lucie; Kromka, Alexander; Jarosova, Marketa; Godier, Greetje; Warnkel, Patrick H

    2015-02-01

    There are relatively few nanotechnologies that can produce nanocomposite scaffolds for cell growth. Electrospinning has emerged as the foremost method of producing nanofibrous biomimetic scaffolds for tissue engineering applications. In this study diamond nanoparticles were integrated into a polymer solution to develop a nanocomposite scaffold containing poly(lactide-co-glycolide) (PLGA) loaded with diamond nanoparticles. To investigate the effect of adding diamond nanoparticles to PLGA scaffolds, primary human mesenchymal stem cells (hMSCs) were seeded on the scaffolds. The cytocompatibility results showed that addition of diamond nanoparticles did not impinge upon cell proliferation, nor was there a cytotoxic cellular response after 9 days in culture. Scanning electron microscopy, transmission electron microscopy, atomic force microscopy and confocal microscopy enabled qualitative characterization of the fibres and revealed cell morphology and number. Furthermore, surface roughness was measured to evaluate diamond nanoparticle modifications, and no significant difference was found between the diamond nanocomposite and pure polymer scaffolds. On the other hand, bright spots on phase images performed by atomic force microscopy suggested a higher hardness at certain points on fibers of the PLGA-nanodiamond composites, which was supported by nanoindentation measurements. This study shows that PLGA nanofibers can be reinforced with nanodiamond without adversely affecting cell behaviour, and thus it sets the foundation for future application of these scaffolds in bone tissue engineering.

  9. Development of an Automated Bone Mineral Density Software Application: Facilitation Radiologic Reporting and Improvement of Accuracy.

    Science.gov (United States)

    Tsai, I-Ta; Tsai, Meng-Yuan; Wu, Ming-Ting; Chen, Clement Kuen-Huang

    2016-06-01

    The conventional method of bone mineral density (BMD) report production by dictation and transcription is time consuming and prone to error. We developed an automated BMD reporting system based on the raw data from a dual energy X-ray absorptiometry (DXA) scanner for facilitating the report generation. The automated BMD reporting system, a web application, digests the DXA's raw data and automatically generates preliminary reports. In Jan. 2014, 500 examinations were randomized into an automatic group (AG) and a manual group (MG), and the speed of report generation was compared. For evaluation of the accuracy and analysis of errors, 5120 examinations during Jan. 2013 and Dec. 2013 were enrolled retrospectively, and the context of automatically generated reports (AR) was compared with the formal manual reports (MR). The average time spent for report generation in AG and in MG was 264 and 1452 s, respectively (p Z scores in AR is 100 %. The overall accuracy of AR and MR is 98.8 and 93.7 %, respectively (p < 0.001). The mis-categorization rate in AR and MR is 0.039 and 0.273 %, respectively (p = 0.0013). Errors occurred in AR and can be grouped into key-in errors by technicians and need for additional judgements. We constructed an efficient and reliable automated BMD reporting system. It facilitates current clinical service and potentially prevents human errors from technicians, transcriptionists, and radiologists.

  10. Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

    Science.gov (United States)

    Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

    2015-05-01

    Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

  11. Free Software Development. 4. Client-Server Implementation of Bone Age Assessment Calculations

    Directory of Open Access Journals (Sweden)

    Sorana Daniela BOLBOACĂ

    2003-03-01

    Full Text Available In pediatrics, bone age also called skeletal maturity, an expression of biological maturity of a child, is an important quantitative measure for the clinical diagnosis of endocrinological problems and growth disorders. The present paper discusses a Java script implementation of Tanner-Whitehouse Method on computer, with complete graphical interface that include pictures and explanations for every bone. The program allows to select a stage (from a set of 7 or 8 stages for every bone (from a set of 20 bones, and also allow user to input some specific data such as natural age, sex, place of residence. Based on TW2 reported values, selected and input data, the program compute the bone age. Java script functions and objects were used in order to make an efficient and adaptive program. Note that in classic way, the program implementation it requires more than 160 groups of instructions only for user interface design. Using of dynamic creation of page, the program became smaller and efficient. The program was tested and put on a web server to serve for directly testing via http service and from where can also be download and runes from a personal computer without internet connection: http://vl.academicdirect.ro/medical_informatics/bone_age/v1.0/

  12. Novel development of carbonate apatite-chitosan scaffolds based on lyophilization technique for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Maretaningtias Dwi Ariani

    2012-09-01

    Full Text Available Background: The natural biopolymer chitosan (Ch is currently regarded as a candidate for bone tissue engineering. However, Ch is poor for cell adhesion and low bone formation ability. In order to enhance cell adhesion and bone formation ability, combination of Ch with carbonate apatite (CA was developed. Purpose: The aim of this study was to make carbonate apatite-chitosan scaffolds (CAChSs and evaluate its osteoconductivity in terms of cell proliferation. Methods: Chitosan scaffolds (ChSs were made by the following procedure. Twenty-five, 50, 100, 200 and 400 mg Ch was dissolved into 5 ml of 2% acetic acid (CH3COOH, shaked for 15 min and neutralized with 15 ml of 0.1 M sodium hydroxide (NaOH solution. After centrifugation, Ch gel was packed into the molds then frozen at -80°C for 2h and dried in a freeze dry machine for 24h. The sponges were subjected to UV radiation for 2h. To make CA-ChSs, 200 mg Ch was selected. After neutralization, 50 mg of 0.06 M CA were added into the 200 mg Ch gel. The structure of CA-ChSs was observed by scanning electron microscope (SEM. Mouse osteoblast-like cell (MC3T3-E1 proliferation in these scaffolds was investigated at 1, 7, 14 and 21 days. Results: Three dimensional porous structures of CA-ChSs were clearly observed by SEM. Proliferated cell numbers in CA-ChSs was significantly higher than those in ChSs (control at each stage (p<0.05. Conclusion: It can be concluded that newly developed CA-ChSs had three-dimensional interconnected porous structure, good handling property and supporting ability of proliferation of osteoblasts. It is suggested that newly developed CA-ChSs could be considered as a scaffolds material for bone tissue enginearing.Latar belakang: Kitosan yang merupakan biopolimer alami dianggap sebagai salah satu kandidat untuk rekayasa jaringan tulang. Namun, kitosan memiliki kelemahan terhadap adhesi sel dan kurang mampu membentuk tulang yang cukup. Untuk meningkatkan adhesi sel dan kemampuan

  13. Transport of membrane-bound mineral particles in blood vessels during chicken embryonic bone development.

    Science.gov (United States)

    Kerschnitzki, Michael; Akiva, Anat; Ben Shoham, Adi; Koifman, Naama; Shimoni, Eyal; Rechav, Katya; Arraf, Alaa A; Schultheiss, Thomas M; Talmon, Yeshayahu; Zelzer, Elazar; Weiner, Stephen; Addadi, Lia

    2016-02-01

    During bone formation in embryos, large amounts of calcium and phosphate are taken up and transported to the site where solid mineral is first deposited. The initial mineral forms in vesicles inside osteoblasts and is deposited as a highly disordered calcium phosphate phase. The mineral is then translocated to the extracellular space where it penetrates the collagen matrix and crystallizes. To date little is known about the transport mechanisms of calcium and phosphate in the vascular system, especially when high transport rates are needed and the concentrations of these ions in the blood serum may exceed the solubility product of the mineral phase. Here we used a rapidly growing biological model, the chick embryo, to study the bone mineralization pathway taking advantage of the fact that large amounts of bone mineral constituents are transported. Cryo scanning electron microscopy together with cryo energy dispersive X-ray spectroscopy and focused-ion beam imaging in the serial surface view mode surprisingly reveal the presence of abundant vesicles containing small mineral particles in the lumen of the blood vessels. Morphologically similar vesicles are also found in the cells associated with bone formation. This observation directly implicates the vascular system in solid mineral distribution, as opposed to the transport of ions in solution. Mineral particle transport inside vesicles implies that far larger amounts of the bone mineral constituents can be transported through the vasculature, without the danger of ectopic precipitation. This introduces a new stage into the bone mineral formation pathway, with the first mineral being formed far from the bone itself.

  14. Sex-specific effects of low-dose gestational estradiol-17β exposure on bone development in porcine offspring.

    Science.gov (United States)

    Flöter, Veronika L; Galateanu, Gabriela; Fürst, Rainer W; Seidlová-Wuttke, Dana; Wuttke, Wolfgang; Möstl, Erich; Hildebrandt, Thomas B; Ulbrich, Susanne E

    2016-07-29

    Estrogens are important for the bone development and health. Exposure to endocrine disrupting chemicals during the early development has been shown to affect the bone phenotype later in life. Several studies have been performed in rodents, while in larger animals that are important to bridge the gap to humans there is a paucity of data. To this end, the pig as large animal model was used in the present study to assess the influence of gestational estradiol-17β (E2) exposure on the bone development of the prepubertal and adult offspring. Two low doses (0.05 and 10μg E2/kg body weight) referring to the 'acceptable daily intake' (ADI) and the 'no observed effect level' (NOEL) as stated for humans, and a high-dose (1000μg E2/kg body weight), respectively, were fed to the sows every day from insemination until delivery. In the male prepubertal offspring, the ADI dose group had a lower strength strain index (p=0.002) at the proximal tibia compared to controls, which was determined by peripheral quantitative computed tomography. Prepubertal females were not significantly affected. However, there was a higher cortical cross-sectional area (CSA) (p=0.03) and total CSA (p=0.02) at the femur midpoint in the adult female offspring of the NOEL dose group as measured by computed tomography. These effects were independent from plasma hormone concentrations (leptin, IGF1, estrogens), which remained unaltered. Overall, sex-specific effects on bone development and non-monotonic dose responses were observed. These results substantiate the high sensitivity of developing organisms to exogenous estrogens.

  15. Nanomaterials promise better bone repair

    OpenAIRE

    Qifei Wang; Jianhua Yan; Junlin Yang; Bingyun Li

    2016-01-01

    Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture rep...

  16. Objectively measured physical activity predicts hip and spine bone mineral content in children and adolescents ages 5 - 15 years: Iowa Bone Development Study

    Directory of Open Access Journals (Sweden)

    Kathleen F Janz

    2014-07-01

    Full Text Available This study examined the association between physical activity (PA and bone mineral content (BMC; g from middle childhood to middle adolescence and compared the impact of vigorous-intensity PA (VPA over moderate- to vigorous-intensity PA (MVPA. Participants from the Iowa Bone Development Study were examined at ages 5, 8, 11, 13, and 15 yr (n=369, 449, 452, 410, 307, respectively. MVPA and VPA (min/day were measured using ActiGraph accelerometers. Anthropometry was used to measure body size and somatic maturity. Spine BMC and hip BMC were measured via dual-energy x-ray absorptiometry. Sex-specific multi-level linear models were fit for spine BMC and hip BMC, adjusted for weight (kg, height (cm, linear age (yr, non-linear age (yr2, and maturity (pre peak height velocity vs. at/post peak height velocity. The interaction effects of PA×maturity and PA×age were tested. We also examined differences in spine BMC and hip BMC between the least (10th percentile and most (90th percentile active participants at each examination period. Results indicated that PA added to prediction of BMC throughout the 10-year follow-up, except MVPA did not predict spine BMC in females. Maturity and age did not modify the PA effect for males nor females. At age 5, the males at the 90th percentile for VPA had 8.5% more hip BMC than males in the 10th percentile for VPA. At age 15, this difference was 2.0%. Females at age 5 in the 90th percentile for VPA had 6.1% more hip BMC than those in the 10th percentile for VPA. The age 15 difference was 1.8%. VPA was associated with BMC at weight-bearing skeletal sites from childhood to adolescence, and the effect was not modified by maturity or age. Our findings indicate the importance of early and sustained interventions that focus on VPA. Approaches focused on MVPA may be inadequate for optimal bone health, particularly for females.

  17. Gpr177, a novel locus for bone-mineral-density and osteoporosis, regulates osteogenesis and chondrogenesis in skeletal development

    OpenAIRE

    Maruyama, Takamitsu; Jiang, Ming; Hsu, Wei

    2013-01-01

    Human genetic analysis has recently identified Gpr177 as a susceptibility locus for bone-mineral-density and osteoporosis. Determining the unknown function of this gene is therefore extremely important to further our knowledge base of skeletal development and disease. The protein encoded by Gpr177 exhibits an ability to modulate the trafficking of Wnt similar to the Drosophila Wls/Evi/Srt. Because of a critical role in Wnt regulation, Gpr177 might be required for several key steps of skeletog...

  18. Loss of VHL in mesenchymal progenitors of the limb bud alters multiple steps of endochondral bone development.

    Science.gov (United States)

    Mangiavini, Laura; Merceron, Christophe; Araldi, Elisa; Khatri, Richa; Gerard-O'Riley, Rita; Wilson, Tremika LeShan; Rankin, Erinn B; Giaccia, Amato J; Schipani, Ernestina

    2014-09-01

    Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements.

  19. Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.

    Directory of Open Access Journals (Sweden)

    Kazuma Ogawa

    Full Text Available (68Ga (T 1/2 = 68 min, a generator-produced nuclide has great potential as a radionuclide for clinical positron emission tomography (PET. Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting (68Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Aspn (n = 2, 5, 8, 11, or 14 with easy-to-handle (67Ga, with the previously described (67Ga-DOTA complex conjugated bisphosphonate, (67Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Aspn by a Fmoc-based solid-phase method, complexes were formed with (67Ga, resulting in (67Ga-DOTA-(Aspn with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of (67Ga-DOTA-(Aspn increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, (67Ga-DOTA-(Asp8, (67Ga-DOTA-(Asp11, and (67Ga-DOTA-(Asp14 showed high accumulation in bone (10.5 ± 1.5, 15.1 ± 2.6, and 12.8 ± 1.7% ID/g, respectively but were barely observed in other tissues at 60 min after injection. Although bone accumulation of (67Ga-DOTA-(Aspn was lower than that of (67Ga-DOTA-Bn-SCN-HBP, blood clearance of (67Ga-DOTA-(Aspn was more rapid. Accordingly, the bone/blood ratios of (67Ga-DOTA-(Asp11 and (67Ga-DOTA-(Asp14 were comparable with those of (67Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of (68Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases.

  20. Bone-Forming Capabilities of a Newly Developed NanoHA Composite Alloplast Infused with Collagen: A Pilot Study in the Sheep Mandible

    Directory of Open Access Journals (Sweden)

    Charles Marin

    2013-01-01

    Full Text Available Lateral or vertical bone augmentation has always been a challenge, since the site is exposed to constant pressure from the soft tissue, and blood supply only exists from the donor site. Although, for such clinical cases, onlay grafting with autogenous bone is commonly selected, the invasiveness of the secondary surgical site and the relatively fast resorption rate have been reported as a drawback, which motivated the investigation of alternative approaches. This study evaluated the bone-forming capability of a novel nanoHA alloplast infused with collagen graft material made from biodegradable polylactic acid/polyglycolic acid versus a control graft material with the same synthesized alloplast without the nanoHA component and collagen infiltration. The status of newly formed bone and the resorption of the graft material were evaluated at 6 weeks in vivo histologically and three dimensionally by means of 3D microcomputed tomography. The histologic observation showed that newly formed bone ingrowth and internal resorption of the block were observed for the experimental blocks, whereas for the control blocks less bone ingrowth occurred along with lower resorption rate of the block material. The three-dimensional observation indicated that the experimental block maintained the external geometry, but at the same time successfully altered the graft material into bone. It is suggested that the combination of numerous factors contributed to the bone ingrowth and the novel development could be an alternative bone grafting choice.

  1. Experiment K-314: Fetal and neonatal rat bone and joint development following in Utero spaceflight

    Science.gov (United States)

    Sabelman, E. E.; Holton, E. M.; Arnaud, C. D.

    1981-01-01

    Infant rat limb specimens from Soviet and U.S. ground-based studies were examined by radiography, macrophotography, histologic sectioning and staining and scanning electron microscopy. A comparison was conducted between vivarium and flight-type diets suggesting that nutritional obesity may adversely affect pregnancy. Data were obtained on maturation of ossification centers, orientation of collagen fibers in bone, tendon and ligaments, joint surface texture and spatial relationships of bones of the hind limb. Computer reconstructions of the knee and hip show promise as a means of investigating the etiology of congenital hip dislocation.

  2. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  3. Research progress on alveolar bone development%牙槽骨发生的研究进展

    Institute of Scientific and Technical Information of China (English)

    欧明明; 黄晓峰; 韩培彦

    2014-01-01

    Absorption and loss of alveolar bone are some of the main reasons of tooth loss. Therefore, clinics must understand how to reconstruct alveolar bone. To date, treatment strategies to rescue or regenerate the alveolar bone are limited. The process of developing biological alveolar bone formation in the early stage may help to understand the mechanism of bone regeneration and benefit clinical treatment. Alveolar bone is partially derived from dental follicle cells. Many growth factors and transcription factors are involved in the development of alveolar bone. In this review, the relationship between alveolar bone formation and many factors will be discussed in detail. This review also highlights recent advances in understanding alveolar bone development with and without varying factors.%牙槽骨再生是牙周组织疾病治疗的根本。牙槽骨发生属于膜内成骨,成骨细胞来源于多潜能神经嵴牙囊间质细胞,伴随着牙体的发生而发生。牙胚由成釉器、牙乳头和牙囊组成,而牙囊则形成牙骨质、牙周膜和牙槽骨。骨形态发生蛋白(BMP)可启动、促进和调节骨的发生、发育、生长、重塑和修复。核心结合因子1可使牙囊间质细胞向成骨细胞分化,对膜内成骨和软骨内成骨有控制作用。成纤维细胞生长因子通过调控骨干细胞复制,成骨细胞分化和程序性死亡,各种细胞及相关因子的表达来控制骨形成。WNT在BMP的刺激下促进成骨细胞分化,增强BMP诱导下的Ⅰ型胶原、特殊骨基质蛋白和骨钙蛋白表达。声音刺猬蛋白、转化生长因子β和肌节同源盒蛋白2在牙槽骨和牙骨质中表达强烈,其基因突变可致牙槽骨丧失。本文就牙槽骨发生与牙囊间的关系以及参与牙槽骨发生的细胞因子等研究进展作一综述。

  4. The interactions of the cells in the development of osteoporotic changes in bones under space flight conditions

    Science.gov (United States)

    Rodionova, Natalia; Kabitskaya, Olga

    2016-07-01

    Using the methods of electron microscopy and autoradiography with ³N-glycine and ³N-thymidine on biosatellites "Bion-11" (Macaca mulatta, the duration of the experiments -10 days), "Bion-M1" (mouse C57 Black, duration of the flight - 30 days) in the experiments with modeled hypokinesia (white rats, hind limbs unloading, the duration of the experiments 28 days) new data about the morpho-functional peculiarities of cellular interactions in adaptive remodeling zones of bone structures under normal conditions and after exposure of animals to microgravity. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and paving endost one as well as to the bone-marrow stromal cells and perivascular cells. As a response to the mechanical stimulus (microgravity) the system of perivascular cell-stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, the number of apoptotic osteoblasts increases. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts, bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn't occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in remodeling loci. These cell reactions

  5. Determining the modulus of intact bovine vertebral cancellous bone tissue: Development and validation of a protocol

    Science.gov (United States)

    Engbretson, Andrew Craig

    Cancellous, or spongy, bone accounts for nearly 80% of the human skeleton's internal surface area, despite comprising only 20% of its mass. It is made up of a network of struts and plates that provide lightweight internal support to mammalian bones. In addition, it often serves as the main interface between the skeletal system and implanted devices such as artificial hips, knees, and fracture fixation devices. However, hip arthroplasties can succumb to loosening of the implant due to bone resorption, which is thought to be caused by a mismatch in both apparent and real stiffness between the device and the surrounding bone. Many studies have attempted to determine the Young's modulus of cancellous bone tissue, but the results are far from being in agreement. Reported values range from less than 1 to nearly 20 GPa. In addition, the small size of trabeculae has made dissection and testing a challenge. In this thesis, whole individual trabeculae from a bovine lumbar spine were tested in three-point bending to determine their Young's modulus using custom-made equipment to fit a miniature single-axis testing device. The device itself was validated by testing materials with moduli ranging from 1 to 200 GPa. The structure of the cancellous bone and the morphology of the individual struts were determined using micro x-ray computed tomography (muXCT). Individual struts were manually isolated from slices made using a low-speed saw under constant lubrication and measured under a stereomicroscope. Samples exhibiting no machined surfaces (and thus deemed to be whole, or "uncut" were compared to struts that had been cut by the saw during sectioning. Validation showed that the system was capable of determining the modulus of materials that were approximately five times stiffer than the expected cancellous modulus (copper, at 115 GPa) to within 10% of published values. This gave confidence in the results for bone. The modulus of the "uncut" specimens was found to be 15.28 2.26 GPa

  6. Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold.

    Science.gov (United States)

    Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Yu; Li, Ruipeng; Wang, Yiwei; Wang, Ling; Wang, Hong; Liu, Tianqing

    2016-06-01

    Using tissue engineering techniques, an artificial osteochondral construct was successfully fabricated to treat large osteochondral defects. In this study, porcine cancellous bones and chitosan/gelatin hydrogel scaffolds were used as substitutes to mimic bone and cartilage, respectively. The porosity and distribution of pore size in porcine bone was measured and the degradation ratio and swelling ratio for chitosan/gelatin hydrogel scaffolds was also determined in vitro. Surface morphology was analyzed with the scanning electron microscope (SEM). The physicochemical properties and the composition were tested by using an infrared instrument. A double layer composite scaffold was constructed via seeding adipose-derived stem cells (ADSCs) induced to chondrocytes and osteoblasts, followed by inoculation in cancellous bones and hydrogel scaffolds. Cell proliferation was assessed through Dead/Live staining and cellular activity was analyzed with IpWin5 software. Cell growth, adhesion and formation of extracellular matrix in composite scaffolds blank cancellous bones or hydrogel scaffolds were also analyzed. SEM analysis revealed a super porous internal structure of cancellous bone scaffolds and pore size was measured at an average of 410 ± 59 μm while porosity was recorded at 70.6 ± 1.7 %. In the hydrogel scaffold, the average pore size was measured at 117 ± 21 μm and the porosity and swelling rate were recorded at 83.4 ± 0.8 % and 362.0 ± 2.4 %, respectively. Furthermore, the remaining hydrogel weighed 80.76 ± 1.6 % of the original dry weight after hydration in PBS for 6 weeks. In summary, the cancellous bone and hydrogel composite scaffold is a promising biomaterial which shows an essential physical performance and strength with excellent osteochondral tissue interaction in situ. ADSCs are a suitable cell source for osteochondral composite reconstruction. Moreover, the bi-layered scaffold significantly enhanced cell proliferation compared to the cells seeded on

  7. Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era.

    Science.gov (United States)

    Karras, S N; Anagnostis, P; Bili, E; Naughton, D; Petroczi, A; Papadopoulou, F; Goulis, D G

    2014-03-01

    Data from animal and human studies implicate maternal vitamin D deficiency during pregnancy as a significant risk factor for several adverse outcomes affecting maternal, fetal, and child health. The possible associations of maternal vitamin D status and offspring bone development comprise a significant public health issue. Evidence from randomized trials regarding maternal vitamin D supplementation for optimization of offspring bone mass is lacking. In the same field, data from observational studies suggest that vitamin D supplementation is not indicated. Conversely, supplementation studies provided evidence that vitamin D has beneficial effects on neonatal calcium homeostasis. Nevertheless, a series of issues, such as technical difficulties of current vitamin D assays and functional interplay among vitamin D analytes, prohibit arrival at safe conclusions. Future studies would benefit from adoption of a gold standard assay, which would unravel the functions of vitamin D analytes. This narrative review summarizes and discusses data from both observational and supplementation studies regarding maternal vitamin D status during pregnancy and offspring bone development.

  8. A study on development of guideline on writing technical document for electrical medical devices: Bone absorptiometric X-ray system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Youl; Kim, Jae Ryang; Kim, Eun Rim; Lee, Jun Ho; Lee, Chang Hyung; Park, Chang Won [Medical Device Research Division, Ministry of Food and Drug Safety, Cheongju (Korea, Republic of)

    2016-06-15

    The market size of the bone absorptiometric X-ray system and the number of its approval by Ministry of Food and Drug Safety (MFDS) has annually increased, with a trend of increasing aging population and osteoporosis patients. For approval of manufactured or imported medical devices in Republic of Korea, it is required to submit its technical document. Therefore, it is need to develop the technical document guideline for the bone absorptiometric X-ray system for manufacturers, importers and reviewers. First of all, the technical documents which were already approved were examined and analyzed through MFDS approval administration system. Second, safety and performance test standards and methods that match international standards were drawn after conducting survey of the market status and the technology development trend for it, with examination and analysis of applicable domestic and overseas standards. Third, by operating industry-research-government cooperation, the guideline draft on writing technical document for the bone absorptiometric X-ray system was discussed, collecting their opinion. As a result, it is suitable to international and domestic condition, includes test evaluation methods and offer various information with appropriate examples to civil petitioner, when they write the technical documents.

  9. Bi-iliac distance and iliac bone position compared to the vertebral column in normal fetal development

    DEFF Research Database (Denmark)

    Hartling, U B; Fischer Hansen, B; Skovgaard, L T;

    2001-01-01

    Prenatal standards of bi-iliac width were not found in the literature based on autopsy investigations, nor was the caudo-cranial position of the ilia compared to the vertebral column. The first purpose of the present study was to establish normal standard values for the bi-iliac distance in fetal...... life, the second to evaluate the level of the iliac bones proportional to the ossified vertebral column. Whole body radiographs in antero-posterior projections from 98 human fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex had not been determined) were analyzed...... caliper. The caudo-cranial position of the iliac bones was evaluated. The present study shows that in normal fetal development there is a continuous linear enlargement of the pelvic region in the transverse and vertical planes. The upper iliac contour stays at the level of the first sacral vertebral body...

  10. Assessment of the Effect of Artesunate on the Developing Bones of Wistar Rat Animal Model of Malaria Treatment

    Directory of Open Access Journals (Sweden)

    Sunday Samuel Adebisi

    2010-02-01

    Full Text Available AIM: Among its contemporaries, artesunate, a semisynthetic artemisinin antimalarial is presently being esteemed above others as a ready combatant against the malaria menace plaguing most parts of the tropics; one, for being less or non-resisted by the parasite and two, less allergy-provoking to the users. However, recent clinical observations and experimental studies had implicated this drug to be embryo-fetal toxic and this had since generated research interests such as this, to ascertain the extent of the effects of artesunate on the morphology, weights and dimensions of the developing Wistar rat bones METHOD: Oral doses of 2mg/kg and 4mg/kg body weight were administered to each experimental pregnant Wistar rat from the 9th to the 11th day of gestation–being the active osteogenic period in this animal. Two rats were sacrificed each day from days 12 to 21 and foetuses retrieved and the following assessed on the skeleton: wet weights, dry weights, ash weights, fat free weights and total body weights, plus dimensions of long bones and pelvic bones. RESULTS: Compared to the control, all the parameters assessed were negatively affected in the treated groups, being more severe in the 4mg/kg rats. CONCLUSION: Artesunate, even at relatively low dosages appears to be hazardous to the structural integrity of bones particularly when administered at critical period of development, a point to note in the global quest to combat malaria cum polio, the presently well acknowledged ravaging twin menace in the tropics. [TAF Prev Med Bull 2010; 9(1.000: 23-28

  11. The Function of HMG-Box Transcription Factors Sox4a and Sox4b in Zebrafish Bone Development and Homeostasis

    Science.gov (United States)

    Aceto, J.; Motte, P.; Martial, J. A.; Muller, M.

    2008-06-01

    In mammals, the Sox4 gene is involved in development of endocardial crests, the brain, the lung, teeth, gonads and lymphocytes. Recently, Sox4 was shown to control bone mass and mineralization in mice. In zebrafish, two homologs for the mammalian Sox4 are present, sox4a and sox4b. Here we investigate the function of the sox4a and sox4b genes in cartilage and bone development in zebrafish. Therefore, we focus our attention on the first bone structures to be formed, the head skeleton and more precisely the pharyngeal cartilage. We show that both genes are expressed in the pharyngeal region, albeit at different time points during development. Double in situ hybridization experiments are used to exactly define the particular tissues where they are expressed. Furthermore, microinjection experiments of antisense oligonucleotides are used to block translation of these specific genes and to define their precise function during cartilage and bone development.

  12. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

  13. Development of a preclinical orthotopic xenograft model of ewing sarcoma and other human malignant bone disease using advanced in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Britta Vormoor

    Full Text Available Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG and Rag2(-/-/γc(-/- mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000-5000 injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised "malignant" bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

  14. Effect of tibial bone resection on the development of fast- and slow-twitch skeletal muscles in foetal sheep.

    Science.gov (United States)

    West, J M; Williams, N A; Luff, A R; Walker, D W

    2000-04-01

    To determine if longitudinal bone growth affects the differentiation of fast- and slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal sheep so that the lower leg was permanently without structural support. At 140 days (term is approximately 147 days) the contractile properties of whole muscles, activation profiles of single fibres and ultrastructure of fast- and slow-twitch muscles from the hindlimbs were studied. The contractile and activation profiles of the slow-twitch soleus muscles were significantly affected by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/- 10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ - and Sr2+ -activation profiles of skinned fibres similar to those from intact hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly change whole muscle twitch contraction time, the fatigue profile or the Ca2+ - and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an increased deposition of glycogen in both soleus and FDL muscles. This study shows that the development of the slow-twitch phenotype is impeded in the absence of the physical support normally provided by the tibial bone. We suggest that longitudinal stretch is an important factor in allowing full expression of the slow-twitch phenotype.

  15. Pou3f4-mediated regulation of ephrin-b2 controls temporal bone development in the mouse.

    Directory of Open Access Journals (Sweden)

    Steven Raft

    Full Text Available The temporal bone encases conductive and sensorineural elements of the ear. Mutations of POU3F4 are associated with unique temporal bone abnormalities and X-linked mixed deafness (DFNX2/DFN3. However, the target genes and developmental processes controlled by POU3F4 transcription factor activity have remained largely uncharacterized. Ephrin-B2 (Efnb2 is a signaling molecule with well-documented effects on cell adhesion, proliferation, and migration. Our analyses of targeted mouse mutants revealed that Efnb2 loss-of-function phenocopies temporal bone abnormalities of Pou3f4 hemizygous null neonates: qualitatively identical malformations of the stapes, styloid process, internal auditory canal, and cochlear capsule were present in both mutants. Using failed/insufficient separation of the stapes and styloid process as a quantitative trait, we found that single gene Efnb2 loss-of-function and compound Pou3f4/Efnb2 loss-of-function caused a more severe phenotype than single gene Pou3f4 loss-of-function. Pou3f4 and Efnb2 gene expression domains overlapped at the site of impending stapes-styloid process separation and at subcapsular mesenchyme surrounding the cochlea; at both these sites, Efnb2 expression was attenuated in Pou3f4 hemizygous null mutants relative to control. Results of immunoprecipitation experiments using chromatin isolated from nascent middle ear mesenchyme supported the hypothesis of a physical association between Pou3f4 and specific non-coding sequence of Efnb2. We propose that Efnb2 is a target of Pou3f4 transcription factor activity and an effector of mesenchymal patterning during temporal bone development.

  16. Development of Thermosensitive Hydrogels of Chitosan, Sodium and Magnesium Glycerophosphate for Bone Regeneration Applications

    Directory of Open Access Journals (Sweden)

    Jana Lisková

    2015-04-01

    Full Text Available Thermosensitive injectable hydrogels based on chitosan neutralized with sodium beta-glycerophosphate (Na-β-GP have been studied as biomaterials for drug delivery and tissue regeneration. Magnesium (Mg has been reported to stimulate adhesion and proliferation of bone forming cells. With the aim of improving the suitability of the aforementioned chitosan hydrogels as materials for bone regeneration, Mg was incorporated by partial substitution of Na-β-GP with magnesium glycerophosphate (Mg-GP. Chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were also loaded with the enzyme alkaline phosphatase (ALP which induces hydrogel mineralization. Hydrogels were characterized physicochemically with respect to mineralizability and gelation kinetics, and biologically with respect to cytocompatibility and cell adhesion. Substitution of Na-β-GP with Mg-GP did not negatively influence mineralizability. Cell biological testing showed that both chitosan/Na-β-GP and chitosan/Na-β-GP/Mg-GP hydrogels were cytocompatible towards MG63 osteoblast-like cells. Hence, chitosan/Na-β-GP/Mg-GP hydrogels can be used as an alternative to chitosan/Na-β-GP hydrogels for bone regeneration applications. However the incorporation of Mg in the hydrogels during hydrogel formation did not bring any appreciable physicochemical or biological benefit.

  17. Development of multi-substituted hydroxyapatite nanopowders as biomedical materials for bone tissue engineering applications.

    Science.gov (United States)

    Baba Ismail, Yanny M; Wimpenny, Ian; Bretcanu, Oana; Dalgarno, Kenneth; El Haj, Alicia J

    2017-02-15

    Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering (BTE) applications. The effect of simultaneous substitution of different levels of carbonate (CO3 ) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow-derived mesenchymal stem cells (hMSCs) were cultured on multi-substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA-1 (0.58wt% Si) and SiCHA-2 (0.45wt% Si) showed missing bands for CO3 and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice. 500°C was considered the most favourable calcination temperature as: (i) the powders produced possessed a similar amount of CO3 (2-8wt%) and Si (<1.0wt%) as present in native bone; and (ii) there was a minimal loss of CO3 and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA-1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA-2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behaviour to a greater extent than other powders. This article is protected by copyright. All rights reserved.

  18. Guided bone regeneration : the influence of barrier membranes on bone grafts and bone defects

    NARCIS (Netherlands)

    Gielkens, Pepijn Frans Marie

    2008-01-01

    Guided bone regeneration (GBR) can be described as the use of a barrier membrane to provide a space available for new bone formation in a bony defect. The barrier membrane protects the defect from in-growth of soft tissue cells and allows bone progenitor cells to develop bone within a blood clot tha

  19. Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

    Energy Technology Data Exchange (ETDEWEB)

    Arioka, Masaki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Takahashi-Yanaga, Fumi, E-mail: yanaga@clipharm.med.kyushu-u.ac.jp [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Sasaki, Masanori [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Yoshihara, Tatsuya; Morimoto, Sachio [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Takashima, Akihiko [Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Oobu (Japan); Mori, Yoshihide [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Sasaguri, Toshiyuki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)

    2013-11-01

    Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β{sup +/−} mice. •The cortical and trabecular bone volumes were increased in GSK-3β{sup +/−} mice. •Regeneration of a partial bone defect was accelerated in GSK-3β{sup +/−} mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β{sup +/−}). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β{sup +/−} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β{sup +/−} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β{sup +/−} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β{sup +/−} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.

  20. Bone Markers

    Science.gov (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  1. Bone scan

    Science.gov (United States)

    ... legs, or spine fractures) Diagnose a bone infection (osteomyelitis) Diagnose or determine the cause of bone pain, ... 2015:chap 43. Read More Broken bone Metabolism Osteomyelitis Review Date 12/10/2015 Updated by: Jatin ...

  2. 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 ...

  3. 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 ...

  4. Long-Term Trend of Bone Development in the Contemporary Teenagers of Chinese Han Nationality

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-hui; YING Chong-liang; WAN Lei; ZHU Guang-you

    2012-01-01

    Objective To further improve the accuracy of bone age identification using the time of secondary ossification center appearance and epiphyseal fusion of 7 joints to estimate the age of living individuals.Methods DR films were taken from 7 parts including sternal end of clavical and the left side of shoulder,elbow,carpal,hip,knee and ankle joints of 1709 individuals who came from eastern China,central China and southern China,whose ages were between 11.0 and 20.0 years.From those 7 joints 24 osteal loci were selected as bone age indexes,which could better reflect age growth of teenagers.The characteristics of secondary ossification center appearance and epiphyseal fusion were observed,and the mean and age range of secondary ossification center appearance and epiphyseal fusion were calculated.Results The fusion time of the 24 epiphyses were advanced at different degrees,the most obvious epiphyses the sternal end of clavicle,scapular acromial end,distal end of the radius,distal end of the ulna,iliac crest,ischial tuberosity,the upper and lower end of tibia and fibula.The appearance time of sternal end of clavicle,scapular acromial end,iliac crest and ischial tuberosity epiphyses were all found to be after the age of 12,and the female's age,approximately 1year ahead of schedule in comparison with the male's.Conclusion The relevant forensic information and data for bone age identification should be updated every 10-15 years so as to provide accurate and objective evidence for court testimony,conviction and sentencing.

  5. Further development of a model of chronic bone marrow aplasia in the busulphan-treated mouse.

    Science.gov (United States)

    Turton, John A; Sones, William R; Andrews, Charles M; Pilling, Andrew M; Williams, Thomas C; Molyneux, Gemma; Rizzo, Sian; Gordon-Smith, Edward C; Gibson, Frances M

    2006-02-01

    Aplastic anaemia (AA) in man is an often fatal disease characterized by pancytopenia of the peripheral blood and aplasia of the bone marrow. AA is a toxic effect of many drugs and chemicals (e.g. chloramphenicol, azathioprine, phenylbutazone, gold salts, penicillamine and benzene). However, there are no widely used or convenient animal models of drug-induced AA. Recently, we reported a new model of chronic bone marrow aplasia (CBMA = AA) in the busulphan (BU)-treated mouse: eight doses of BU (10.50 mg/kg) were administered to female BALB/c mice over a period of 23 days; CBMA was evident at day 91/112 post-dosing with significantly reduced erythrocytes, platelets, leucocytes and nucleated bone marrow cell counts. However, mortality was high (49.3%). We have now carried out a study to modify the BU-dosing regime to induce CBMA without high mortality, and investigated the patterns of cellular responses in the blood and marrow in the post-dosing period. Mice (n = 64/65) were dosed 10 times with BU at 0 (vehicle control), 8.25, 9.0 and 9.75 mg/kg over 21 days and autopsied at day 1, 23, 42, 71, 84, 106 and 127 post-dosing (n = 7-15); blood and marrow samples were examined. BU induced a predictable bone marrow depression at day 1 post-dosing; at day 23/42 post-dosing, parameters were returning towards normal during a period of recovery. At day 71, 84, 106 and 127 post-dosing, a stabilized, late-stage, nondose-related CBMA was evident in BU-treated mice, with decreased erythrocytes, platelets and marrow cell counts, and increased MCV. At day 127 post-dosing, five BU-treated mice showed evidence of lymphoma. In this study, mortality was low, ranging from 3.1% (8.25 mg/kg BU) to 12.3% (9.75 mg/kg BU). It is concluded that BU at 9.0 mg/kg (or 9.25 mg/kg) is an appropriate dose level to administer (10 times over 21 days) to induce CBMA at approximately day 50-120 post-dosing.

  6. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

    Directory of Open Access Journals (Sweden)

    Ryan E. Tomlinson

    2016-09-01

    Full Text Available Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.

  7. Development of Composite Scaffolds for Load-Bearing Segmental Bone Defects

    Directory of Open Access Journals (Sweden)

    Marcello Pilia

    2013-01-01

    Full Text Available The need for a suitable tissue-engineered scaffold that can be used to heal load-bearing segmental bone defects (SBDs is both immediate and increasing. During the past 30 years, various ceramic and polymer scaffolds have been investigated for this application. More recently, while composite scaffolds built using a combination of ceramics and polymeric materials are being investigated in a greater number, very few products have progressed from laboratory benchtop studies to preclinical testing in animals. This review is based on an exhaustive literature search of various composite scaffolds designed to serve as bone regenerative therapies. We analyzed the benefits and drawbacks of different composite scaffold manufacturing techniques, the properties of commonly used ceramics and polymers, and the properties of currently investigated synthetic composite grafts. To follow, a comprehensive review of in vivo models used to test composite scaffolds in SBDs is detailed to serve as a guide to design appropriate translational studies and to identify the challenges that need to be overcome in scaffold design for successful translation. This includes selecting the animal type, determining the anatomical location within the animals, choosing the correct study duration, and finally, an overview of scaffold performance assessment.

  8. Bone, joint and tooth development in mucopolysaccharidoses: relevance to therapeutic options.

    Science.gov (United States)

    Oussoren, E; Brands, M M M G; Ruijter, G J G; der Ploeg, A T van; Reuser, A J J

    2011-11-01

    The mucopolysaccharidoses (MPS) are prominent among the lysosomal storage diseases. The intra-lysosomal accumulation of glycosaminoglycans (GAGs) in this group of diseases, which are caused by several different enzyme deficiencies, induces a cascade of responses that affect cellular functions and maintenance of the extra-cellular matrix. Against the background of normal tissue-specific processes, this review summarizes and discusses the histological and biochemical abnormalities reported in the bones, joints, teeth and extracellular matrix of MPS patients and animal models. With an eye to the possibilities and limitations of reversing the pathological changes in the various tissues, we address therapeutic challenges, and present a model in which the cascade of pathologic events is depicted in terms of primary and secondary events.

  9. Expression and regulation of the decoy bone morphogenetic protein receptor BAMBI in the developing avian face.

    Science.gov (United States)

    Higashihori, Norihisa; Song, Yiping; Richman, Joy M

    2008-05-01

    Here, we examine the expression and regulation of the gene BAMBI, a kinase-deficient decoy receptor capable of interacting with type I bone morphogenetic protein (BMP) receptors in avian embryos. Initially, expression was limited to the endoderm during neurula and pharyngula stages. From embryonic day 3.5 (stage 20) and onward, BAMBI expression almost perfectly overlapped with known expression patterns for BMP4, particularly in the face and limbs. We performed bead implant experiments in the face to see which signals could be repressing or promoting expression of BAMBI. Our data point to retinoids and BMPs as being major positive regulators of BAMBI expression; however, fibroblast growth factor 2 acts to repress BAMBI. Furthermore, retinoic acid is likely to act directly on BAMBI as induction occurs in the presence of cycloheximide. The data suggested that BAMBI could be used to regulate Bmp signaling during tissue interactions that are an integral part of facial morphogenesis.

  10. Treatment of large diaphyseal bone defect of the tibia by the "fibula pro tibia" technique: application in developing countries.

    Science.gov (United States)

    Gayito, René Castro; Priuli, Giambattista; Traore, Sidi Yaya; Barbier, Olivier; Docquier, Pierre-Louis

    2015-03-01

    Large segmental bone defects of the tibia may be due to infections, high-energy fractures, congenital diseases or tumors and represent a challenge for both the physician and the patient. In developing countries, the use of expansive techniques is not possible so that amputation is sometimes proposed. However, an alternative technique for limb salvage, applicable in developing countries consists of tibialization of the ipsilateral fibula. This technique is also called "Fibula pro Tibia", fibular transfer to the tibia or fibular centralization. We report this transfer in 4 patients with an average defect length of 11.8 cm. Union between the transferred fibula and the tibia was obtained in all patients, for both proximal and distal junctions, after an average time of 8.5 months (range, 4 to 18 months). Three patients returned to a normal walking function while one was still limping, but was able to walk independently without need of crutches.

  11. Development of glass-ceramic scaffolds for bone tissue engineering: characterisation, proliferation of human osteoblasts and nodule formation.

    Science.gov (United States)

    Vitale-Brovarone, C; Verné, E; Robiglio, L; Appendino, P; Bassi, F; Martinasso, G; Muzio, G; Canuto, R

    2007-03-01

    Glass-ceramic macroporous scaffolds for tissue engineering have been developed using a polyurethane sponge template and bioactive glass powders. The starting glass (CEL2) belongs to the system SiO(2)-P(2)O(5)-CaO-MgO-Na(2)O-K(2)O and has been synthesised by a conventional melting-quenching route. A slurry of CEL2 powder, polyvinyl alcohol and water has been prepared in order to coat, by impregnation, the polymeric template. An optimised thermal treatment was then use to remove the sponge and to sinter the glass powders, leading to a glass-ceramic replica of the template. Morphological observations, image analyses, mechanical tests and in vitro tests showed that the obtained devices are good candidates as scaffolds for bone-tissue engineering, in terms of pore-size distribution, pore interconnection, surface roughness, and both bioactivity and biocompatibility. In particular, a human osteoblast cell line (MG-63) seeded onto the scaffold after a standardised preconditioning route in simulated body fluid showed a high degree of cell proliferation and a good ability to produce calcium nodules. The obtained results were enhanced by the addition of bone morphogenetic proteins after cell seeding.

  12. 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 ...

  13. Increased IL-6 expression in osteoclasts is necessary but not sufficient for the development of Paget's disease of bone.

    Science.gov (United States)

    Teramachi, Jumpei; Zhou, Hua; Subler, Mark A; Kitagawa, Yukiko; Galson, Deborah L; Dempster, David W; Windle, Jolene J; Kurihara, Noriyoshi; Roodman, G David

    2014-06-01

    Measles virus nucleocapsid protein (MVNP) expression in osteoclasts (OCLs) and mutation of the SQSTM1 (p62) gene contribute to the increased OCL activity in Paget's disease (PD). OCLs expressing MVNP display many of the features of PD OCLs. Interleukin-6 (IL-6) production is essential for the pagetic phenotype, because transgenic mice with MVNP targeted to OCLs develop pagetic OCLs and lesions, but this phenotype is absent when MVNP mice are bred to IL-6(-/-) mice. In contrast, mutant p62 expression in OCL precursors promotes receptor activator of NF-κB ligand (RANKL) hyperresponsivity and increased OCL production, but OCLs that form have normal morphology, are not hyperresponsive to 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ), nor produce elevated levels of IL-6. We previously generated p62(P394L) knock-in mice (p62KI) and found that although OCL numbers were increased, the mice did not develop pagetic lesions. However, mice expressing both MVNP and p62KI developed more exuberant pagetic lesions than mice expressing MVNP alone. To examine the role of elevated IL-6 in PD and determine if MVNP mediates its effects primarily through elevation of IL-6, we generated transgenic mice that overexpress IL-6 driven by the tartrate-resistant acid phosphatase (TRAP) promoter (TIL-6 mice) and produce IL-6 at levels comparable to MVNP mice. These were crossed with p62KI mice to determine whether IL-6 overexpression cooperates with mutant p62 to produce pagetic lesions. OCL precursors from p62KI/TIL-6 mice formed greater numbers of OCLs than either p62KI or TIL-6 OCL precursors in response to 1,25-(OH)2 D3 . Histomorphometric analysis of bones from p62KI/TIL-6 mice revealed increased OCL numbers per bone surface area compared to wild-type (WT) mice. However, micro-quantitative CT (µQCT) analysis did not reveal significant differences between p62KI/TIL-6 and WT mice, and no pagetic OCLs or lesions were detected in vivo. Thus, increased IL-6 expression in OCLs from p62KI mice

  14. Developing a bone mineral density test result letter to send to patients: a mixed-methods study

    Directory of Open Access Journals (Sweden)

    Edmonds SW

    2014-06-01

    Full Text Available Stephanie W Edmonds,1,2 Samantha L Solimeo,3 Xin Lu,1 Douglas W Roblin,4,8 Kenneth G Saag,5 Peter Cram6,7 1Department of Internal Medicine, 2College of Nursing, University of Iowa, Iowa City, IA, USA; 3Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA; 4Kaiser Permanente of Atlanta, Atlanta, GA, USA; 5Department of Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA; 6Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 7University Health Network and Mount Sinai Hospital, Toronto, ON, Canada; 8School of Public Health, Georgia State University, Atlanta, GA, USA Purpose: To use a mixed-methods approach to develop a letter that can be used to notify patients of their bone mineral density (BMD results by mail that may activate patients in their bone-related health care. Patients and methods: A multidisciplinary team developed three versions of a letter for reporting BMD results to patients. Trained interviewers presented these letters in a random order to a convenience sample of adults, aged 50 years and older, at two different health care systems. We conducted structured interviews to examine the respondents’ preferences and comprehension among the various letters. Results: A total of 142 participants completed the interview. A majority of the participants were female (64.1% and white (76.1%. A plurality of the participants identified a specific version of the three letters as both their preferred version (45.2%; P<0.001 and as the easiest to understand (44.6%; P<0.01. A majority of participants preferred that the letters include specific next steps for improving their bone health. Conclusion: Using a mixed-methods approach, we were able to develop and optimize a printed letter for communicating a complex test result (BMD to patients. Our results may offer guidance to clinicians, administrators, and researchers who are

  15. Giant Cell Tumor Developing in Paget’s Disease of Bone: A Case Report with Review of Literature

    Science.gov (United States)

    Verma, Vivek; Puri, Ajay; Shah, Sanket; Rekhi, Bharat; Gulia, Ashish

    2016-01-01

    Introduction: Paget’s disease of bone (PDB) is a disease of elderly characterized by disorganized bone remodeling. Development of secondary neoplasm in PDB is a known but rare phenomenon. Development of giant cell tumor in PDB (GCT-PDB) is extremely rare, and little is known about its etiopathogenesis and management. We present a case report of such a development with a review of the literature and the role of various new modalities of treatment available in the management of this rare condition. Case Report: A 40-year-old gentleman presented with back pain and on evaluation was diagnosed as a case of polyostotic PDB. He was treated with intravenous bisphosphonates, calcium, and vitamin D supplements. After an asymptomatic period of 3-year, he presented with a gluteal mass involving ilium and sacrum which was confirmed as GCT on biopsy. Serial angioembolization was attempted but mass progressed, so surgery performed with excision and curettage of the lesion. He presented with a local recurrence 2 years later with a large soft tissue component. He was started on denosumab, RANKL inhibitor, with the aim to downstage the lesion. The patient showed a good response after 6 doses with reduction in soft tissue mass followed by which he underwent surgery with partial T-1 internal hemipelvectomy and curettage of sacrum. Currently, the patient is asymptomatic at a follow-up of 15 months. Conclusion: GCT-PDB is a rare phenomenon occurring mainly in polyostotic PDB and is associated with more severe manifestations of the disease. The management is challenging and requires multimodality management. Pharmacological agents include use of bisphosphonates and RANK ligand inhibitor - denosumab. Although surgery is the mainstay of treatment for GCT, other modalities of treatment such as RANK ligand inhibitors (denosumab), selective arterial embolization, or radiation therapy has to be used for inoperable cases or where surgery would be functionally too morbid, especially in cases

  16. Mimicking the nanostructure of bone matrix to regenerate bone

    Directory of Open Access Journals (Sweden)

    Robert Kane

    2013-11-01

    Full Text Available Key features of bone tissue structure and composition are capable of directing cellular behavior toward the generation of new bone tissue. Bone tissue, as well as materials derived from bone, have a long and successful history of use as bone grafting materials. Recent developments in design and processing of synthetic scaffolding systems has allowed the replication of the bone's desirable biological activity in easy to fabricate polymeric materials with nano-scale features exposed on the surface. The biological response to these new tissue-engineering scaffold materials oftentimes exceeds that seen on scaffolds produced using biological materials.

  17. Bone marrow aspiration

    Science.gov (United States)

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

  18. Toxicity and biocompatibility profile of 3D bone scaffold developed by Universitas Indonesia: A preliminary study

    Science.gov (United States)

    Rahyussalim A., J.; Kurniawati, T.; Aprilya, D.; Anggraini, R.; Ramahdita, Ghiska; Whulanza, Yudan

    2017-02-01

    Scaffold as a biomaterial must fulfill some requirements to be safely implanted to the human body. Toxicity and biocompatibility test are needed to evaluate scaffold material in mediating cell proliferation and differentiation, secreting extracelullar matrix and carrying biomolecular signals for cell communication. An in vitro study with mesenchymal stem cells consisted of direct contact test and indirect contact test using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay was conducted on 4 scaffolds made of poly-L-lactic acid (PLA), polyvinyl alcohol (PVA), and hydroxyapatite-poly (vinyl alcohol) composite. There were cells-substrate adhesion impairment, morphological changes, cell death and reduction in cell proliferation seen at 2nd and 6th day in most tested scaffold. Cell count result at day-6 showed proliferation inhibition of more than 50% cell death (inhibition value >50) in all tested scaffold. In MTT assay, two scaffolds were proven non-toxic. In conclusion, various scaffold materials showed different toxicity effect. The toxicity and biocompatibility profile in this study is a preliminary data for further research aiming to use those local-made scaffolds to fill human bone defect in various needs.

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

    Science.gov (United States)

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

    2017-01-01

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

  20. Material properties and in vitro biocompatibility of a newly developed bone cement

    Directory of Open Access Journals (Sweden)

    Elke Mitzner

    2009-01-01

    Full Text Available In this study mechanical properties and biocompatibility (In Vitro of a new bone cement were investigated. A new platform technology named COOL is a variable composite of dissolved, chemically modified PMMA and different bioceramics. COOL cures at body temperature via a classical cementation reaction. Compressive strengths ranging from 3.6 ± 0.8 to 62.8 ± 1.3 MPa and bending strengths ranging from 9.9 ± 2.4 to 26.4 ± 3.0 MPa were achieved with different COOL formulations. Porosity varied between 31 and 43%. Varying the components of each formulation mechanical properties and porosity could be adjusted. In Vitro biocompatibility studies with primary human osteoblasts (pHOB in direct contact with different COOL formulations, did not reveal any signs of toxicity. In contrast to Refobacin® R, cells incubated with COOL showed similar density, viability and ALP activity compared to control, if specimen were added immediately to the cell monolayer after preparation. In conclusion, COOL has promising mechanical properties in combination with high biocompatibility In Vitro and combines different advantages of both CPCs and PMMA cements by avoiding some of the respective shortcomings.

  1. Features of the physical development, calcium-phosphorus metabolism and mineral density of the bones in children with chronic lung diseases

    Directory of Open Access Journals (Sweden)

    Olya Sharipova

    2011-03-01

    Full Text Available We have studied features of physical development, calcium-phosphorus metabolism and mineral density of the bones in children with chronic lung diseases. Comparison of received results with the standards of physical development in children and adolescents has shown the most significant differences in ages of 10, 11 and 15 years old who had the stature level lower than average. The data obtained suggest that children with this pathology undergoes substantial adverse changes in the main somatomertric indicators and bone mineral density, the degree of which depends on the nature of the primary lesion in the bronchopulmonary system, and duration and severity of disease.

  2. BONES, TEACHER'S GUIDE.

    Science.gov (United States)

    Elementary Science Study, Newton, MA.

    THIS GUIDE WAS DEVELOPED FOR USE WITH THE ELEMENTARY SCIENCE STUDY UNIT ON "BONES.""BONES" HAS BEEN TAUGHT IN THE FOURTH GRADE AND REQUIRES FROM 10 TO 25 LESSONS, DEPENDING ON THE NUMBER OF ACTIVITIES USED. THE GUIDE DOES NOT PROVIDE DETAILED INSTRUCTION FOR CONDUCTING CLASSES, BUT RATHER SOME POSSIBLE ACTIVITIES, AND LEAVES THE DAY-TO-DAY…

  3. Histological analyses demonstrate the temporary contribution of yolk sac, liver, and bone marrow to hematopoiesis during chicken development.

    Directory of Open Access Journals (Sweden)

    Priscila Tavares Guedes

    Full Text Available The use of avian animal models has contributed to the understanding of many aspects of the ontogeny of the hematopoietic system in vertebrates. However, specific events that occur in the model itself are still unclear. There is a lack of consensus, among previous studies, about which is the intermediate site responsible for expansion and differentiation of hematopoietic cells, and the liver's contribution to the development of this system. Here we aimed to evaluate the presence of hematopoiesis in the yolk sac and liver in chickens, from the stages of intra-aortic clusters in the aorta-genital ridges-mesonephros (AGM region until hatching, and how it relates to the establishment of the bone marrow. Gallus gallus domesticus L. embryos and their respective yolk sacs at embryonic day 3 (E3 and up to E21 were collected and processed according to standard histological techniques for paraffin embedding. The slides were stained with hematoxylin-eosin, Lennert's Giemsa, and Sirius Red at pH 10.2, and investigated by light microscopy. This study demonstrated that the yolk sac was a unique hematopoietic site between E4 and E12. Hematopoiesis occurred in the yolk sac and bone marrow between E13 and E20. The liver showed granulocytic differentiation in the connective tissue of portal spaces at E15 and onwards. The yolk sac showed expansion of erythrocytic and granulocytic lineages from E6 to E19, and E7 to E20, respectively. The results suggest that the yolk sac is the major intermediate erythropoietic and granulopoietic site where expansion and differentiation occur during chicken development. The hepatic hematopoiesis is restricted to the portal spaces and represented by the granulocytic lineage.

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

    OpenAIRE

    Mengoni, Marlène

    2012-01-01

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

  5. Development of the long bones in the hands and feet of children: radiographic and MR imaging correlation

    Energy Technology Data Exchange (ETDEWEB)

    Laor, Tal [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Clarke, Jeffrey P. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Children' s Healthcare of Atlanta, Department of Radiology, Atlanta, GA (United States); Yin, Hong [Children' s Healthcare of Atlanta, Department of Pathology, Atlanta, GA (United States)

    2016-04-15

    The long bones of the hands and feet in children have an epiphyseal end with a secondary center of ossification and an adjacent transverse physis. In contrast to other long bones in the body, the opposite end in the hands and feet, termed the non-epiphyseal end, is characterized by direct metaphyseal extension of bone to complete terminal ossification. The purpose of this pictorial essay is to illustrate the developmental stages of each end of the long bones of the hands and feet with radiographic and MR imaging to provide a foundation from which to differentiate normal from abnormal growth. (orig.)

  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. Influence of gain-of-function mutation (Ser252Trp in fibroblast growth factor receptor 2 gene on long bone development

    Directory of Open Access Journals (Sweden)

    Peng CHEN

    2013-07-01

    Full Text Available Objective To observe the early postnatal long bone development in Fgfr2+/S252W mutant mice and littermate wild-type (WT mice, and explore the effect of continued function enhancement of fibroblast growth factor receptor 2 (FGFR2 gene on endochondral ossification. Methods A mouse model of Fgfr2+/S252W simulated human Apert syndrome was reproduced by knock-in technique, and then the gain-of-function mutation Fgfr2+/S252W mice and littermate WT mice were obtained after breeding and identification. Three Fgfr2+/S252W and same number of WT mice were sacrificed at 7, 10, 14 and 28 postnatal days respectively, and the morphology of long bone was examined with X-ray and Micro CT, the structure of bone and cartilage was observed by HE staining, and the expression of gene in growth plate was observed by immunohistochemical analysis. Results Fgfr2+/S252W mouse model exhibited typical craniosynostosis and brachycephalium of Apert syndrome, accompanied by short stature, growth retardation of long bone, delayed appearance of secondary ossification center, decrease of bone density and trabecula number. HE staining showed noticeable shortened zones of proliferation and hypertrophic chondrocytes, irregularity of cell arrangement, and small hypertrophic chondrocytes in the growth plates of the mutant mice. Immunohistochemical analysis revealed that the expression of genes related to chondrocytes proliferation and differentiation was decreased in mutant mice. Conclusions Gain-of-function mutation in FGFR2 may lead to abnormal development of long bone in mice. FGFR2 may have the function of regulating the development both of osteoblast and chondrocyte lineages, and play an important role in the process of skeletal development.

  8. Adrenal gland and bone.

    Science.gov (United States)

    Hardy, Rowan; Cooper, Mark S

    2010-11-01

    The adrenal gland synthesizes steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. Both cortisol and adrenal androgens can have powerful effects on bone. The overproduction of cortisol in Cushing's disease leads to a dramatic reduction in bone density and an increase risk of fracture. Overproduction of adrenal androgens in congenital adrenal hyperplasia (CAH) leads to marked changes in bone growth and development with early growth acceleration but ultimately a significant reduction in final adult height. The role of more physiological levels of glucocorticoids and androgens on bone metabolism is less clear. Cortisol levels measured in elderly individuals show a weak correlation with measures of bone density and change in bone density over time with a high cortisol level associated with lower bone density and more rapid bone loss. Cortisol levels and the dynamics of cortisol secretion change with age which could also explain some age related changes in bone physiology. It is also now clear that adrenal steroids can be metabolized within bone tissue itself. Local synthesis of cortisol within bone from its inactive precursor cortisone has been demonstrated and the amount of cortisol produced within osteoblasts appears to increase with age. With regard to adrenal androgens there is a dramatic reduction in levels with aging and several studies have examined the impact that restoration of these levels back to those seen in younger individuals has on bone health. Most of these studies show small positive effects in women, not men, but the skeletal sites where benefits are seen varies from study to study.

  9. Bone scanning in otolaryngology.

    Science.gov (United States)

    Noyek, A M

    1979-09-01

    Modern radionuclide bone scanning has introduced a new concept in physiologic and anatomic diagnostic imaging to general medicine. As otolaryngologists must diagnose and treat disease in relation to the bony and/or cartilaginous supporting structures of the neurocranium and upper airway, this modality should be included in the otolaryngologist's diagnostic armamentarium. It is the purpose of this manuscript to study the specific applications of bone scanning to our specialty at this time, based on clinical experience over the past three years. This thesis describes the development of bone scanning in general (history of nuclear medicine and nuclear physics; history of bone scanning in particular). General concepts in nuclear medicine are then presented; these include a discussion of nuclear semantics, principles of radioactive emmissions, the properties 99mTc as a radionuclide, and the tracer principle. On the basis of these general concepts, specific concepts in bone scanning are then brought forth. The physiology of bone and the action of the bone scan agents is presented. Further discussion considers the availability and production of the bone scan agent, patient factors, the gamma camera, the triphasic bone scan and the ultimate diagnostic principle of the bone scan. Clinical applications of bone scanning in otolaryngology are then presented in three sections. Proven areas of application include the evaluation of malignant tumors of the head and neck, the diagnosis of temporomandibular joint disorders, the diagnosis of facial fractures, the evaluation of osteomyelitis, nuclear medicine imaging of the larynx, and the assessment of systemic disease. Areas of adjunctive or supplementary value are also noted, such as diagnostic imaging of meningioma. Finally, areas of marginal value in the application of bone scanning are described.

  10. Hypercalciuric Bone Disease

    Science.gov (United States)

    Favus, Murray J.

    2008-09-01

    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

  11. Nanomaterials promise better bone repair

    Directory of Open Access Journals (Sweden)

    Qifei Wang

    2016-10-01

    Full Text Available Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture repair. Next, the review discusses the applications of nanomaterials for bone fracture repair, with a focus on the recent breakthroughs such as nanomaterials leading to precise immobilization of growth factors at the molecular level, promoting vascularization without the use of growth factors, and re-loading therapeutic agents after implantation. The review concludes with perspectives on challenges and future directions for developing nanomaterials for improved bone fracture repair.

  12. Development of a nomogram model predicting current bone scan positivity in patients treated with androgen-deprivation therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Michael eKattan

    2014-10-01

    Full Text Available Purpose: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations.Materials and Methods: A retrospective chart review of bone scan records (conventional 99mTc-scintigraphy of 1,293 patients who received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011. Multivariable logistic regression analysis was used to identify variables suitable for inclusion in the nomogram. The probability of current bone scan positivity was determined using these variables and the predictive accuracy of the nomogram was quantified by concordance index.Results: In total, 2,681 bone scan records were analyzed and 636 patients had a positive result. Overall, the median pre-scan prostate-specific antigen (PSA level was 2.4 ng/ml; median PSA doubling time (PSADT was 5.8 months. At the time of a positive scan, median PSA level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0 months. Five variables were included in the nomogram: number of previous negative bone scans after initiating ADT, PSA level, Gleason grade sum, and history of radical prostatectomy and radiotherapy. A concordance index value of 0.721 was calculated for the nomogram. This was a retrospective study based on limited data in patients treated in a large cancer centre who underwent conventional 99mTc bone scans, which themselves have inherent limitations. Conclusions: This is the first nomogram to predict current bone scan positivity in ADT-treated prostate cancer patients, providing high predictive accuracy.

  13. Biochemical development of subchondral bone from birth until age eleven months and the influence of physical activity

    NARCIS (Netherlands)

    Brama, P.A.J.; TeKoppele, J.M.; Bank, R.A.; Barneveld, A.; Weeren, P.R. van

    2002-01-01

    Subchondral bone provides structural support to the overlying articular cartilage, and plays an important role in osteochondral diseases. There is growing insight that the mechanical features of bone are related to the biochemistry of the collagen network and the mineral content. In the present stud

  14. Gpr177, a novel locus for bone mineral density and osteoporosis, regulates osteogenesis and chondrogenesis in skeletal development.

    Science.gov (United States)

    Maruyama, Takamitsu; Jiang, Ming; Hsu, Wei

    2013-05-01

    Human genetic analysis has recently identified Gpr177 as a susceptibility locus for bone mineral density and osteoporosis. Determining the unknown function of this gene is therefore extremely important to furthering our knowledge base of skeletal development and disease. The protein encoded by Gpr177 exhibits an ability to modulate the trafficking of Wnt, similar to the Drosophila Wls/Evi/Srt. Because it plays a critical role in Wnt regulation, Gpr177 might be required for several key steps of skeletogenesis. To overcome the early lethality associated with the inactivation of Gpr177 in mice, conditional gene deletion is used to assess its functionality. Here we report the generation of four different mouse models with Gpr177 deficiency in various skeletogenic cell types. The loss of Gpr177 severely impairs development of the craniofacial and body skeletons, demonstrating its requirement for intramembranous and endochondral ossifications, respectively. Defects in the expansion of skeletal precursors and their differentiation into osteoblasts and chondrocytes suggest that Wnt production and signaling mediated by Gpr177 cannot be substituted. Because the Gpr177 ablation impairs Wnt secretion, we therefore identify the sources of Wnt proteins essential for osteogenesis and chondrogenesis. The intercross of Wnt signaling between distinct cell types is carefully orchestrated and necessary for skeletogenesis. Our findings lead to a proposed mechanism by which Gpr177 controls skeletal development through modulation of autocrine and paracrine Wnt signals in a lineage-specific fashion.

  15. Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients

    NARCIS (Netherlands)

    Görzer, Irene; Puchhammer-Stöckl, Elisabeth; van Esser, Joost W J; Niesters, Hubert G M; Cornelissen, Jan J

    2007-01-01

    The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between th

  16. Development of a food group-based diet score and its assocation with bone mineral density in the elderly: the Rotterdam Study

    NARCIS (Netherlands)

    Jonge, de E.A.L.; Kiefte-de Jong, J.C.; Groot, de C.P.G.M.; Voortman, T.; Schoufour, J.D.; Zillikens, M.C.; Hofman, A.; Uitterlinden, A.G.; Franco, O.H.; Rivadeneira, F.

    2015-01-01

    No diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b) to examine the association of the BMD-Di

  17. Development of a food group-based diet score and its association with bone mineral density in the elderly: The Rotterdam study

    NARCIS (Netherlands)

    E.A.L. de Jonge (Ester); J.C. Kiefte-de Jong (Jessica); L.C.P.G.M. de Groot (Lisette); R.G. Voortman (Trudy); J.D. Schoufour (Josje); M.C. Zillikens (Carola); A. Hofman (Albert); A.G. Uitterlinden (André); O.H. Franco (Oscar); F. Rivadeneira Ramirez (Fernando)

    2015-01-01

    textabstractNo diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD) in the elderly. Our aims were (a) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b) to examine the association o

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

    Science.gov (United States)

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

  19. Computerized geometric features of carpal bone for bone age estimation

    Institute of Scientific and Technical Information of China (English)

    Chi-Wen Hsieh; Tai-Lang Jong; Yi-Hong Chou; Chui-Mei Tiu

    2007-01-01

    Background Bone age development is one of the significant indicators depicting the growth status of children.However, bone age assessment is an heuristic and tedious work for pediatricians. We developed a computerized bone age estimation system based on the analysis of geometric features of carpal bones.Methods The geometric features of carpals were extracted and analyzed to judge the bone age of children by computerized shape and area description. Four classifiers, linear, nearest neighbor, back-propagation neural network,and radial basis function neural network, were adopted to categorize bone age. Principal component and discriminate analyses were employed to improve assorting accuracy.Results The hand X-ray films of 465 boys and 444 girls served as our database. The features were extracted from carpal bone images, including shape, area, and sequence. The proposed normalization area ratio method was effective in bone age classification by simulation. Besides, features statistics showed similar results between the standard of the Greulich and Pyle atlas and our database.Conclusions The bone area has a higher discriminating power to judge bone age. The ossification sequence of trapezium and trapezoid bones between Taiwanese and the atlas of the GP method is quite different. These results also indicate that carpal bone assessment with classification of neural networks can be correct and practical.

  20. Development of primers for detection of heat-treated cetacean materials in porcine meat and bone meal.

    Science.gov (United States)

    Shinoda, Naoki; Yoshida, Tomotaro; Kusama, Toyoko; Takagi, Masami; Onodera, Takashi; Sugiura, Katsuaki

    2009-07-01

    The feed ban introduced after the detection of the first case of bovine spongiform encephalopathy in 2001 in Japan has been modified to allow some of the previously prohibited animal materials to be used in animal feed. Recently, porcine materials were allowed to be used in feed for pigs, poultry, and fish. Materials from other mammals, including whales, remain prohibited. In the absence of a method to detect the prohibited whale materials in porcine materials, there is a possibility that the whale materials are being used for feed for pigs, poultry, and fish. To detect illegal use of whale materials mixed with porcine materials, we have developed PCR primers specific to a group of most cetacean species, using a computer-based method we developed previously. The primer sets were capable of detecting whale meat meal that had been autoclaved at 133 degrees C for up to 20 min. The detection limit of whale material in porcine meat and bone meal was 0.1%.

  1. Development of a guided bone regeneration device using salicylic acid-poly(anhydride-ester) polymers and osteoconductive scaffolds.

    Science.gov (United States)

    Mitchell, Ashley; Kim, Brian; Cottrell, Jessica; Snyder, Sabrina; Witek, Lukasz; Ricci, John; Uhrich, Kathryn E; O'Connor, J Patrick

    2014-03-01

    Successful repair of craniofacial and periodontal tissue defects ideally involves a combined therapy that includes inflammation modulation, control of soft tissue infiltration, and bone regeneration. In this study, an anti-inflammatory polymer, salicylic acid-based poly(anhydride-ester) (SAPAE) and a three-dimensional osteoconductive ceramic scaffold were evaluated as a combined guided bone regeneration (GBR) system for concurrent control of inflammation, soft tissue ingrowth, and bone repair in a rabbit cranial defect model. At time periods of 1, 3, and 8 weeks, five groups were compared: (1) scaffolds with a solid ceramic cap (as a GBR structure); (2) scaffolds with no cap; (3) scaffolds with a poly(lactide-glycolide) cap; (4) scaffolds with a slow release SAPAE polymer cap; and (5) scaffolds with a fast release SAPAE polymer cap. Cellular infiltration and bone formation in these scaffolds were evaluated to assess inflammation and bone repair capacity of the test groups. The SAPAE polymers suppressed inflammation and displayed no deleterious effect on bone formation. Additional work is warranted to optimize the anti-inflammatory action of the SAPAE, GBR suppression of soft tissue infiltration, and stimulation of bone formation in the scaffolds and create a composite device for successful repair of craniofacial and periodontal tissue defects.

  2. The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone Lesion Development

    Science.gov (United States)

    2015-09-01

    mice to the level as in the Col/Tgfbr2 KO mice (Figure 7A, B&C). These effects were correlated with respective changes in FGFR1, FGFR4 , and p-AKT...development. bFGF binds to FGFR1 and FGFR4 to regulate downstream AKT signaling. Key Research Accomplishments: 1. We found that TGF-β signaling in

  3. Functional upregulation of nav1.8 sodium channels on the membrane of dorsal root Ganglia neurons contributes to the development of cancer-induced bone pain.

    Directory of Open Access Journals (Sweden)

    Xiao-Dan Liu

    Full Text Available We have previously reported that enhanced excitability of dorsal root ganglia (DRG neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.

  4. Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia.

    Science.gov (United States)

    Jaako, Pekka; Flygare, Johan; Olsson, Karin; Quere, Ronan; Ehinger, Mats; Henson, Adrianna; Ellis, Steven; Schambach, Axel; Baum, Christopher; Richter, Johan; Larsson, Jonas; Bryder, David; Karlsson, Stefan

    2011-12-01

    Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Among these genes, ribosomal protein S19 (RPS19) is mutated most frequently. Generation of animal models for diseases like DBA is challenging because the phenotype is highly dependent on the level of RPS19 down-regulation. We report the generation of mouse models for RPS19-deficient DBA using transgenic RNA interference that allows an inducible and graded down-regulation of Rps19. Rps19-deficient mice develop a macrocytic anemia together with leukocytopenia and variable platelet count that with time leads to the exhaustion of hematopoietic stem cells and bone marrow failure. Both RPS19 gene transfer and the loss of p53 rescue the DBA phenotype implying the potential of the models for testing novel therapies. This study demonstrates the feasibility of transgenic RNA interference to generate mouse models for human diseases caused by haploinsufficient expression of a gene.

  5. B cell development in the bone marrow is regulated by homeostatic feedback exerted by mature B cells

    Directory of Open Access Journals (Sweden)

    Gitit eShahaf

    2016-03-01

    Full Text Available Cellular homeostasis in the B cell compartment is strictly imposed to balance cell production and cell loss. However, it is not clear whether B cell development in the bone marrow (BM is an autonomous process or subjected to regulation by the peripheral B cell compartment. To specifically address this question, we used mice transgenic for human CD20, where effective depletion of B lineage cells is obtained upon administration of mouse-anti-human CD20 antibodies, in the absence of any effect on other cell lineages and/or tissues. We followed the kinetics of B cell return to equilibrium by BrdU labeling and flow cytometry and analyzed the resulting data by mathematical modeling. Labeling was much faster in depleted mice. Compared to control mice, B cell-depleted mice exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher cell death and lower differentiation in the immature B cell compartment. We validated the first result by analysis of the expression of Ki67, the nuclear protein expressed in proliferating cells, and the second using Annexin-V staining. Collectively, our results suggest that B lymphopoiesis is subjected to homeostatic feedback mechanisms imposed by mature B cells in the peripheral compartment.

  6. Development and validation of technique for in-vivo 3D analysis of cranial bone graft survival

    Science.gov (United States)

    Bernstein, Mark P.; Caldwell, Curtis B.; Antonyshyn, Oleh M.; Ma, Karen; Cooper, Perry W.; Ehrlich, Lisa E.

    1997-05-01

    Bone autografts are routinely employed in the reconstruction of facial deformities resulting from trauma, tumor ablation or congenital malformations. The combined use of post- operative 3D CT and SPECT imaging provides a means for quantitative in vivo evaluation of bone graft volume and osteoblastic activity. The specific objectives of this study were: (1) Determine the reliability and accuracy of interactive computer-assisted analysis of bone graft volumes based on 3D CT scans; (2) Determine the error in CT/SPECT multimodality image registration; (3) Determine the error in SPECT/SPECT image registration; and (4) Determine the reliability and accuracy of CT-guided SPECT uptake measurements in cranial bone grafts. Five human cadaver heads served as anthropomorphic models for all experiments. Four cranial defects were created in each specimen with inlay and onlay split skull bone grafts and reconstructed to skull and malar recipient sites. To acquire all images, each specimen was CT scanned and coated with Technetium doped paint. For purposes of validation, skulls were landmarked with 1/16-inch ball-bearings and Indium. This study provides a new technique relating anatomy and physiology for the analysis of cranial bone graft survival.

  7. Transcutaneous Raman Spectroscopy of Bone

    Science.gov (United States)

    Maher, Jason R.

    Clinical diagnoses of bone health and fracture risk typically rely upon measurements of bone density or structure, but the strength of a bone is also dependent upon its chemical composition. One technology that has been used extensively in ex vivo, exposed-bone studies to measure the chemical composition of bone is Raman spectroscopy. This spectroscopic technique provides chemical information about a sample by probing its molecular vibrations. In the case of bone tissue, Raman spectra provide chemical information about both the inorganic mineral and organic matrix components, which each contribute to bone strength. To explore the relationship between bone strength and chemical composition, our laboratory has contributed to ex vivo, exposed-bone animal studies of rheumatoid arthritis, glucocorticoid-induced osteoporosis, and prolonged lead exposure. All of these studies suggest that Raman-based predictions of biomechanical strength may be more accurate than those produced by the clinically-used parameter of bone mineral density. The utility of Raman spectroscopy in ex vivo, exposed-bone studies has inspired attempts to perform bone spectroscopy transcutaneously. Although the results are promising, further advancements are necessary to make non-invasive, in vivo measurements of bone that are of sufficient quality to generate accurate predictions of fracture risk. In order to separate the signals from bone and soft tissue that contribute to a transcutaneous measurement, we developed an overconstrained extraction algorithm that is based upon fitting with spectral libraries derived from separately-acquired measurements of the underlying tissue components. This approach allows for accurate spectral unmixing despite the fact that similar chemical components (e.g., type I collagen) are present in both soft tissue and bone and was applied to experimental data in order to transcutaneously detect, to our knowledge for the first time, age- and disease-related spectral

  8. Development and characterization of reinforced poly(L-lactide) scaffolds for bone tissue engineering.

    Science.gov (United States)

    Park, Joo-Eon; Todo, Mitsugu

    2011-05-01

    Novel reinforced poly(L-lactic acid) (PLLA) scaffolds such as solid shell, porous shell, one beam and two beam reinforced scaffolds were developed to improve the mechanical properties of a standard PLLA scaffold. Experimental results clearly indicated that the compressive mechanical properties such as the strength and the modulus are effectively improved by introducing the reinforcement structures. A linear elastic model consisting of three phases, that is, the reinforcement, the porous matrix and the boundary layer was also introduced in order to predict the compressive moduli of the reinforced scaffolds. The comparative study clearly showed that the simple theoretical model can reasonably predict the moduli of the scaffolds with three phase structures. The failure mechanism of the solid shell and the porous shell reinforced scaffolds under compression were found to be buckling of the solid shell and localized buckling of the struts constructing the pores in the porous shell, respectively. For the beam reinforced scaffolds, on the contrary, the primary failure mechanism was understood to be micro-cracking within the beams and the subsequent formation of the main-crack due to the coalescence of the micro-racks. The biological study was exhibited that osteoblast-like cells, MC3T3-E1, were well adhered and proliferated on the surfaces of the scaffolds after 12 days culturing.

  9. Bone cutting.

    Science.gov (United States)

    Giraud, J Y; Villemin, S; Darmana, R; Cahuzac, J P; Autefage, A; Morucci, J P

    1991-02-01

    Bone cutting has always been a problem for surgeons because bone is a hard living material, and many osteotomes are still very crude tools. Technical improvement of these surgical tools has first been their motorization. Studies of the bone cutting process have indicated better features for conventional tools. Several non-conventional osteotomes, particularly ultrasonic osteotomes are described. Some studies on the possible use of lasers for bone cutting are also reported. Use of a pressurised water jet is also briefly examined. Despite their advantages, non-conventional tools still require improvement if they are to be used by surgeons.

  10. Allen's rule revisited: temperature influences bone elongation during a critical period of postnatal development.

    Science.gov (United States)

    Serrat, Maria A

    2013-10-01

    Limbs of animals raised at warm ambient temperature are significantly and permanently longer than those of siblings housed in the cold. These highly reproducible lab results closely parallel the ecogeographical tenet described by Allen's extremity size rule, which states that appendage length correlates with temperature and latitude. It is unclear what mechanisms underlie these differences and in what pattern they emerge, since the morphology is traditionally thought to reflect naturally selected genomic adaptations for thermoregulation. This study tests the a posteriori hypothesis that adult extremity length is subject to substantial modification by temperature during a brief but critical period of early postnatal development. Weanling mice (N = 28) were divided into three groups and housed at 7°C, 21°C, or 27°C for eight weeks. Tail lengths and body mass were measured weekly. Mass did not differ at any age. Analysis of tail elongation curves revealed two distinct phases: an initial period of rapid temperature-sensitive growth in which elongation rate was directly impacted by temperature; and a second phase of continued growth in which rates were identical among groups. Comparable growth reactions occur in response to other environmental variables such as exercise, suggesting that the skeleton is most responsive to external stimuli during a window of heightened sensitivity when growth occurs most rapidly. Knowledge of the timing and degree to which growth plasticity permits mammals to immediately adjust to novel temperature conditions will be important for analyzing skeletal variation in fluctuating climates, particularly for assessing factors that may accelerate skeletal evolution at temperature extremes.

  11. Evolution, development, and plasticity of the human brain: from molecules to bones.

    Science.gov (United States)

    Hrvoj-Mihic, Branka; Bienvenu, Thibault; Stefanacci, Lisa; Muotri, Alysson R; Semendeferi, Katerina

    2013-10-30

    Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species. The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation, and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research.

  12. Evolution, development, and plasticity of the human brain: from molecules to bones

    Directory of Open Access Journals (Sweden)

    Branka eHrvoj-Mihic

    2013-10-01

    Full Text Available Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species.The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research.

  13. ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13

    Science.gov (United States)

    Zhao, Gexin; Yokoyama, Tadafumi; Huang, Yan; Bishop, Kevin; Maduro, Valerie; Accardi, John; Toro, Camilo; Boerkoel, Cornelius F.; Gahl, William A.; Duan, Xiaohong; Malicdan, May Christine V.; Lin, Shuo

    2017-01-01

    ATP6V1H is a component of a large protein complex with vacuolar ATPase (V-ATPase) activity. We identified two generations of individuals in which short stature and osteoporosis co-segregated with a mutation in ATP6V1H. Since V-ATPases are highly conserved between human and zebrafish, we generated loss-of-function mutants in atp6v1h in zebrafish through CRISPR/Cas9-mediated gene knockout. Homozygous mutant atp6v1h zebrafish exhibited a severe reduction in the number of mature calcified bone cells and a dramatic increase in the expression of mmp9 and mmp13. Heterozygous adults showed curved vertebra that lack calcified centrum structure and reduced bone mass and density. Treatment of mutant embryos with small molecule inhibitors of MMP9 and MMP13 significantly restored bone mass in the atp6v1h mutants. These studies have uncovered a new, ATP6V1H-mediated pathway that regulates bone formation, and defines a new mechanism of disease that leads to bone loss. We propose that MMP9/MMP13 could be therapeutic targets for patients with this rare genetic disease. PMID:28158191

  14. Inducible models of bone loss.

    Science.gov (United States)

    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions.

  15. Vertebral Development and Ossification in the Siberian Sturgeon (Acipenser Baerii), with New Insights on Bone Histology and Ultrastructure of Vertebral Elements and Scutes.

    Science.gov (United States)

    Leprévost, Amandine; AzaÏs, Thierry; Trichet, Michael; Sire, Jean-Yves

    2017-03-01

    In order to improve our knowledge on the vertebral development, structure and mineralization in Acipenseriformes, we undertook a study in a growth series of reared Siberian sturgeons (Acipenser baerii) using in toto clear and stain specimens, histological and ultrastructural observations, X-ray micro-tomography, and solid state NMR analyses. Scutes were also studied to compare the tissue structure and mineralization of endoskeletal and dermal skeletal elements. This study completes and clarifies previous investigations on vertebral development and architecture in sturgeons, and brings original data on the structure of (i) the perichondral bone that is progressively deposited around the vertebral elements during ontogeny, (ii) the typical cartilage composing these elements, and (iii) the scutes. In addition we provide data on the mineralization process, on the nature of the bone mineral phase, and on the growth dynamics of the vertebral elements. Anat Rec, 300:437-449, 2017. © 2016 Wiley Periodicals, Inc.

  16. Electrophoretic deposition of organic/inorganic composite coatings on metallic substrates for bone replacement applications: mechanisms and development of new bioactive materials based on polysaccharides

    OpenAIRE

    Cordero Arias, Luis Eduardo

    2015-01-01

    Regarding the need to improve the usually encountered osteointegration of metallic implants with the surrounding body tissue in bone replacement applications, bioactive organic/inorganic composite coatings on metallic substrates were developed in this work using electrophoretic deposition (EPD) as coating technology. In the present work three polysaccharides, namely alginate, chondroitin sulfate and chitosan were used as the organic part, acting as the matrix of the coating and enabling the c...

  17. Decreased Bone Mineral Density Is an Independent Predictor for the Development of Atherosclerosis: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Chenyi Ye

    Full Text Available There is conflicting evidence regarding the association between decreased bone mineral density (BMD and atherosclerosis. To this end, we performed a systematic review and meta-analysis to clarify the association.To identify relevant studies, PubMed, Embase, and the Cochrane Library were systematically searched up to November 2015. All observational and comparative studies directly investigating the relationship between decreased BMD and clinical consequences of atherosclerotic vascular abnormalities, including carotid artery calcification (CAC, cardiovascular disease (CAD, and coronary artery disease (CAD were obtained, without limitation of language or publication year.A total of 25 studies involving 10,299 patients were included. The incidence of atherosclerotic vascular abnormalities was significantly increased in low BMD patients, compared to patients with normal BMD (OR, 1.81, 95% CI [1.01, 2.19], p<0.00001. Similar results were also observed for postmenopausal women (OR, 2.23, 95% CI [1.72, 2.89], p<0.00001. Subgroup analyses of osteopenia, osteoporosis, and normal BMD also revealed that the combined ORs for the incidence of atherosclerotic vascular abnormalities increased as BMD decreased. Of note, after adjusting for age, sex, body mass index (BMI and other vascular risk factors, decreased BMD remained significantly associated with the incidence of atherosclerotic vascular abnormalities (OR, 2.96, 95% CI [2.25, 3.88], p < 0.00001.Based on the results of this study, decreased BMD is an independent predictor for the development of atherosclerosis in elderly individuals. Moreover, the risk of atherosclerotic vascular abnormalities increased as BMD decreased. Future studies focusing on individuals with different severities of atherosclerosis and comorbidities are of interest.

  18. Effects of masticatory movement on cranial bone mass and micromorphology of osteocytes and osteoblasts in developing rats.

    Science.gov (United States)

    Kawakami, Toshikazu; Takise, Sadafumi; Fuchimoto, Takafumi; Kawata, Hiroshi

    2009-01-01

    In order to evaluate the influence of masticatory movement on cranial bone mineral density (BMD) and osteocyte and osteoblast micromorphology, we conducted a study in rats fed with solid feed (n=10) and powdered feed (n=10). Cranial BMD was measured by dual X-ray absorptiometry (DXA). Osteocyte morphology was evaluated by light microscopy. In addition, some of the tissue was treated with EDTA-KOH to digest the bone matrix and prepare osteocyte samples. Micromorphology of the osteocytes was examined by scanning electron microscopy (SEM). Bone mineral content (BMC) was significantly higher in the solid feed group (1.86 +/- 0.11 g) than in the powdered feed group (1.63 +/- 0.09 g) (p micromorphology.

  19. Bone x-ray

    Science.gov (United States)

    ... or broken bone Bone tumors Degenerative bone conditions Osteomyelitis (inflammation of the bone caused by an infection) ... Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Osteomyelitis Paget disease of the bone Rickets X-ray ...

  20. Estimation of In vivo Cancellous Bone Elasticity

    Science.gov (United States)

    Otani, Takahiko; Mano, Isao; Tsujimoto, Toshiyuki; Yamamoto, Tadahito; Teshima, Ryota; Naka, Hiroshi

    2009-07-01

    The effect of decreasing bone density (a symptom of osteoporosis) is greater for cancellous bone than for dense cortical bone, because cancellous bone is metabolically more active. Therefore, the bone density or bone mineral density of cancellous bone is generally used to estimate the onset of osteoporosis. Elasticity or elastic constant is a fundamental mechanical parameter and is directly related to the mechanical strength of bone. Accordingly, elasticity is a preferable parameter for assessing fracture risk. A novel ultrasonic bone densitometer LD-100 has been developed to determine the mass density and elasticity of cancellous bone with a spatial resolution comparable to that of peripheral quantitative computed tomography. Bone density and bone elasticity are evaluated using ultrasonic parameters based on fast and slow waves in cancellous bone by modeling the ultrasonic wave propagation path. Elasticity is deduced from the measured bone density and the propagation speed of the fast wave. Thus, the elasticity of cancellous bone is approximately expressed by a cubic equation of bone density.

  1. Printing bone : the application of 3D fiber deposition for bone tissue engineering

    NARCIS (Netherlands)

    Fedorovich, N.E.

    2011-01-01

    Bone chips are used by orthopaedic surgeons for treating spinal trauma and to augment large bone defects. A potential alternative to autologous bone is regeneration of bone tissue in the lab by developing hybrid implants consisting of osteogenic (stem) cells seeded on supportive matrices. Applicatio

  2. Development of a new carbon nanotube–alginate–hydroxyapatite tricomponent composite scaffold for application in bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Rajesh R

    2015-10-01

    Full Text Available Rajendiran Rajesh, Y Dominic Ravichandran Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore, India Abstract: In recent times, tricomponent scaffolds prepared from naturally occurring polysaccharides, hydroxyapatite, and reinforcing materials have been gaining increased attention in the field of bone tissue engineering. In the current work, a tricomponent scaffold with an oxidized multiwalled carbon nanotube (fMWCNT–alginate–hydroxyapatite with the required porosity was prepared for the first time by a freeze-drying method and characterized using analytical techniques. The hydroxyapatite for the scaffold was isolated from chicken bones by thermal calcination at 800°C. The Fourier transform infrared spectra and X-ray diffraction data confirmed ionic interactions and formation of the fMWCNT–alginate–hydroxyapatite scaffold. Interconnected porosity with a pore size of 130–170 µm was evident from field emission scanning electron microscopy. The total porosity calculated using the liquid displacement method was found to be 93.85%. In vitro biocompatibility and cell proliferation on the scaffold was checked using an MG-63 cell line by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and cell attachment by Hoechst stain assay. In vitro studies showed better cell proliferation, cell differentiation, and cell attachment on the prepared scaffold. These results indicate that this scaffold could be a promising candidate for bone tissue engineering. Keywords: chicken bone, hydroxyapatite, alginate, tissue engineering

  3. Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model

    Science.gov (United States)

    Mercatali, Laura; La Manna, Federico; Groenewoud, Arwin; Casadei, Roberto; Recine, Federica; Miserocchi, Giacomo; Pieri, Federica; Liverani, Chiara; Bongiovanni, Alberto; Spadazzi, Chiara; de Vita, Alessandro; van der Pluijm, Gabri; Giorgini, Andrea; Biagini, Roberto; Amadori, Dino; Ibrahim, Toni; Snaar-Jagalska, Ewa

    2016-01-01

    Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model. PMID:27556456

  4. Development of a Patient-Derived Xenograft (PDX of Breast Cancer Bone Metastasis in a Zebrafish Model

    Directory of Open Access Journals (Sweden)

    Laura Mercatali

    2016-08-01

    Full Text Available Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231. The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT, revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.

  5. Validation of a Non-Targeted LC-MS Approach for Identifying Ancient Proteins: Method Development on Bone to Improve Artifact Residue Analysis

    Directory of Open Access Journals (Sweden)

    Andrew Barker

    2015-09-01

    Full Text Available Identification of protein residues from prehistoric cooking pottery using mass spectrometry is challenging because proteins are removed from original tissues, are degraded from cooking, may be poorly preserved due to diagenesis, and occur in a palimpsest of exogenous soil proteins. In contrast, bone proteins are abundant and well preserved. This research is part of a larger method-development project for innovation and improvement of liquid chromatography – mass spectrometry analysis of protein residues from cooking pottery; here we validate the potential of our extraction and characterization approach via application to ancient bone proteins. Because of its preservation potential for proteins and given that our approach is destructive, ancient bone identified via skeletal morphology represents an appropriate verification target. Proteins were identified from zooarchaeological turkey (Meleagris gallopavo Linnaeus Phasianidae, rabbit (Lagomorpha, and squirrel (Sciuridae remains excavated from ancient pueblo archaeological sites in southwestern Colorado using a non-targeted LC-MS/MS approach. The data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD002440. Improvement of highly sensitive targeted LC-MS/MS approaches is an avenue for future method development related to the study of protein residues from artifacts such as stone tools and pottery.

  6. GPR30 disrupts the balance of GABAergic and glutamatergic transmission in the spinal cord driving to the development of bone cancer pain.

    Science.gov (United States)

    Luo, Jie; Huang, Xiaoxia; Li, Yali; Li, Yang; Xu, Xueqin; Gao, Yan; Shi, Ruoshi; Yao, Wanjun; Liu, Juying; Ke, Changbin

    2016-11-08

    Cancer induced bone pain is a very complicated clinical pain states that has proven difficult to be treated effectively due to poorly understand of underlying mechanism, but bone cancer pain (BCP) seems to be enhanced by a state of spinal sensitization. In the present study, we showed that carcinoma tibia implantation induced notable pain sensitization and up-regulation of G-protein-coupled estrogen receptor (GPR30) in the spinal cord of rats which was reversed by GPR30 knockdown. Further studies indicated that upregulation of GPR30 induced by cancer implantation resulted in a select loss of γ-aminobutyric acid-ergic (GABAergic) neurons and functionally diminished the inhibitory transmission due to reduce expression of the vesicular GABA transporter (VGAT). GPR30 contributed to spinal cord disinhibition by diminishing the inhibitory transmission via upregulation of α1 subunit and downregulation of γ2 subunits. GPR30 also facilitated excitatory transmission by promoting functional up-regulation of the calcium/calmodulin-dependent protein kinase II α (CaMKII α) in glutamatergic neurons and increasing the clustering of the glutamate receptor subunit 1 (GluR1) subunit to excitatory synapse.Taken together, GPR30 contributed to the development of BCP by both facilitating excitatory transmission and inhibiting inhibitory transmission in the spinal cord. Our findings provide the new spinal disinhibition and sensitivity mechanisms underlying the development of bone cancer pain.

  7. Investigating the impact of socioeconomic status on the effectiveness of a pamphlet on achieving and maintaining bone health in breast cancer survivors: a patient education resource development primer.

    Science.gov (United States)

    Adirim, Tara; Chafranskaia, Aleksandra; Nyhof-Young, Joyce

    2012-03-01

    Considerable need exists to raise awareness of breast cancer (BC) treatment-induced bone loss and provide management and preventative strategies. We describe the development and evaluation process of an educational pamphlet for BC survivors on achieving and maintaining bone health. A Participatory Design approach was used. The pamphlet was first critically evaluated by interdisciplinary healthcare professionals and less vulnerable members of the target audience prior to evaluation by 45 BC survivors, who completed two questionnaires inquiring about demographics and pamphlet evaluation and satisfaction. Pamphlet effectiveness was correlated with income and education to determine differences between socioeconomic groups. Perceived knowledge increased significantly after reading the brochure for all groups. Socioeconomic status had no impact on pamphlet effectiveness. This methodological approach is presented as a blueprint to promote knowledge translation in cancer patient education contexts aiming to provide cancer patients with the best possible resources for effective self-management of their conditions.

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

    Science.gov (United States)

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

    2013-08-01

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

  9. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  10. Bone graft

    Science.gov (United States)

    ... around the area. The bone graft can be held in place with pins, plates, or screws. Why ... Orthopaedic Surgery, San Francosco, CA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  11. Development of a low grade lymphoma in the mastoid bone in a patient with atypical Cogan’s syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Chris Kalogeropoulos

    2015-05-01

    Full Text Available Cogan’s syndrome is a rare disorder characterized by ocular and audiovestibular manifestations in its typical form and caries a wide variety of atypical manifestations. It is considered as an autoimmune disease. We present the first case in the literature of a 67 year old woman with the development of low grade non-Hodgkin lymphoma (NHL in the mastoid bone in a pre-existing history of atypical Cogan’s syndrome. The anatomical development of NHL was to a “target” organ of Cogan’s syndrome, which is the inner ear.

  12. Bone Remodeling Monitor

    Science.gov (United States)

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

    2009-01-01

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

  13. [Effects of phosphatidylinositol-3 kinase/protein kinase b/bone morphogenetic protein-15 pathway on the follicular development in the mammalian ovary].

    Science.gov (United States)

    Wu, Yan-qing; Chen, Li-yun; Zhang, Zheng-hong; wang, Zheng-chao

    2013-04-01

    In mammals, ovarian follicle is made of an oocyte with its surrounding granulosa cells and theca cells. Follicular growth and development is a highly coordinated programmable process, which guarantees the normal oocyte maturation and makes it having the fertilizing capacity. The paracrine and autocrine between oocytes and granulosa cells are essential for the follicular development to provide a suitable microenvironment. Phosphatidylinositol-3 kinase /protein kinase B is one of these important regulatory signaling pathways during this developmental process, and bone morphogenetic protein-15 an oocyte-specific secreted signal molecule, which regulates the follicular development by paracrine in the mammalian ovary. The present article overviewed the role of phosphatidylinositol-3 kinase / protein kinase B signaling during the follicular development based on our previous investigation about protein kinase B /forkhead transcription factor forkhead family of transcription factors -3a, and then focused on the regulatory effects of bone morphogenetic protein-15, as a downstream signal molecule of phosphatidylinositol-3 kinase / forkhead family of transcription factors -3a pathway, on ovarian follicular development, which helped to further understand the molecular mechanism regulating the follicular development and to treat ovarian diseases like infertility.

  14. Low Bone Density

    Science.gov (United States)

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

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

    Directory of Open Access Journals (Sweden)

    Karin Golan

    2013-09-01

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

  16. Bone marrow transplant

    Science.gov (United States)

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  17. Bone disease of primary hyperoxaluria in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Ring, E.; Wendler, H.; Zobel, G. (Graz Univ. (Austria). Abt. fuer Kinderheilkunde); Ratschek, M. (Graz Univ. (Austria). Abt. fuer Pathologie)

    1989-11-01

    A patient with primary hyperoxaluria type I in infancy is reported. He had renal insufficiency, but urolithiasis was absent. Demonstration of diffuse nephrocalcinosis by renal ultrasound contributed to early diagnosis. Prolonged survival leads to extensive extrarenal oxalate deposition. Repeated skeletal surveys showed the development and the progression of severe hyperoxaluria-related bone disease. Translucent metaphyseal bands with sclerotic margins, wide areas of rarefaction at the ends of the long bones, and translucent rims around the epiphyses and the tarsal bones were signs of disordered bone growth. Bone density generally increased with time indicating progressive sclerosis due to oxalate deposition in the previously normal bone structure. (orig.).

  18. [CHARACTERISTICS OF OSTEOCYTE CELL LINES FROM BONES FORMED AS A RESULT OF MEMBRANOUS (SKULL BONES) AND CHONDRAL (LONG BONES) OSSIFICATION].

    Science.gov (United States)

    Avrunin, A S; Doktorov, A A

    2016-01-01

    The aim of this work was to analyze the literature data and the results of authors' own research, to answer the question--if the osteocytes of bone tissues resulting from membranous and chondral ossification, belong to one or to different cell lines. The differences between the cells of osteocyte lines derived from bones resulting from membranous and chondral ossification were established in: 1) the magnitude of the mechanical signal, initiating the development of the process of mechanotransduction; 2) the nature of the relationship between the magnitude of the mechanical signal that initiates the reorganization of the architecture of bone structures and the resource of their strength; in membranous bones significantly lower mechanical signal caused a substantially greater increment of bone strength resource; 3) the biological activity of bone structures, bone fragments formed from membranous tissue were more optimal for transplantation; 4) the characteristics of expression of functional markers of bone cells at different stages of their differentiation; 5) the nature of the reaction of bone cells to mechanical stress; 6) the sensitivity of bone cells to one of the factors controlling the process of mechanotransduction (PGI2); 7) the functioning of osteocytes during lactation. These differences reflect the functional requirements to the bones of the skeleton--the supporting function in the bones of the limbs and the shaping and protection in the bones of the cranial vault. These data suggest that the results of research conducted on the bones of the skull, should not be transferred to the entire skeleton as a whole.

  19. Pyrazinamide potential effects on male rats DNA fragmentation, bone type I collagen amino acid composition, reproductive capability and posterity antenatal and postnatal development.

    Science.gov (United States)

    Bondarenko, Larysa B; Shayakhmetova, Ganna M; Byshovets, Taisiya F; Kovalenko, Valentina M

    2012-01-01

    Current therapeutic regimens with first-line antitubercular agents are associated with a high rate of adverse effects which can lead to therapeutic failure. Understanding the nature and the severity of these effects is important for treatment optimization. The aim of present study was to investigate pyrazinamide potential effects on male rats DNA fragmentation, amino acid composition of bone type I collagen, reproductive capability and their posterity antenatal and postnatal development. Wistar albino male rats (160-200 g b.w.) were divided into three groups: I--received pyrazinamide per os at a dose of 1000 mg/kg b.w./day, II--at a dose of 2000 mg/kg b.w./day, in both groups it was given for 60 days; III--control. After 60 days of the experiment, rats of the experimental (groups I and II) and control groups were mated with intact virgin females. The amino acids contents of male rat bone type I collagens were determined using amino acid analyzer, epididymis and testis DNA fragmentation--electrophoretically; posterity antenatal development indices and postnatal development--by standard procedures. The study of pyrazinamide effects (administered in different doses) on males bone type I collagen amino acid contents and testis DNA fragmentation demonstrated the presence of dose-dependent pyrazinamide-mediated quantitative and qualitative changes in male rat reproductive organs DNA and extracellular matrix proteins in comparison with control. Changes in nucleic acids and proteins structure were accompanied by alterations in processes of fertilization (with intact females), embryogenesis and by lowering of posterity survival.

  20. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.

    2001-01-01

    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  1. Characteristics of Bone Development in Children with Cerebral Palsy%脑性瘫痪儿童的骨发育特点分析

    Institute of Scientific and Technical Information of China (English)

    李泽萍; 沈敏; 程慧; 赵菁; 牛秀莲; 姚雪华; 顾丽慧; 陈娟娟

    2015-01-01

    目的:观察3~7岁脑瘫患儿骨发育、身体形态发育方面的特点。方法3~7岁脑瘫患儿男女各50例,由经培训的专业人员对入组患儿身高、体重、左右上肢长、左右手骨龄进行测量。结果各年龄段男女患儿骨龄均低于实际年龄1岁左右(P0.05)。脑瘫患儿身高增长规律及增幅与正常儿童基本一致,体重增长规律与正常儿童相比稍有不同。左右上肢长均同步增长,增长幅度呈现减缓趋势,左右侧无显著性差异(P>0.05)。结论脑瘫患儿骨发育落后于生活年龄,身高增长接近正常儿童,发育无明显偏侧差异。%Objective To observe the characteristics of bone development and body development in 3-7 years old children with cerebral palsy. Methods 50 girls and 50 boys aged 3-7 years with cerebral palsy were included. Their height, weight, length of right and left upper ex-tremities, and both hands bone age were measured by trained professionals. Results Their bone ages of both hands were 1 year younger than actual age (P0.05). Their height growth was in line with the normal children, while the weight growth was a little different. Both sides of upper limbs growed synchronously, and slowed down with the time. There was no significant difference in both sides (P>0.05). Conclusion The bone development of children with cerebral palsy lags behind the life age. Their height growth is close to normal children. The development shows no no significant lateral dominance.

  2. [Bone transplant].

    Science.gov (United States)

    San Julián, M; Valentí, A

    2006-01-01

    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands.

  3. Virtual Temporal Bone Anatomy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Background The Visible Human Project(VHP) initiated by the U.S. National Library of Medicine has drawn much attention and interests from around the world. The Visible Chinese Human (VCH) project has started in China. The current study aims at acquiring a feasible virtual methodology for reconstructing the temporal bone of the Chinese population, which may provide an accurate 3-D model of important temporal bone structures that can be used in teaching and patient care for medical scientists and clinicians. Methods A series of sectional images of the temporal bone were generated from section slices of a female cadaver head. On each sectional image, SOIs (structures of interest) were segmented by carefully defining their contours and filling their areas with certain gray scale values. The processed volume data were then inducted into the 3D Slicer software(developed by the Surgical Planning Lab at Brigham and Women's Hospital and the MIT AI Lab) for resegmentation and generation of a set of tagged images of the SOIs. 3D surface models of SOIs were then reconstructed from these images. Results The temporal bone and structures in the temporal bone, including the tympanic cavity, mastoid cells, sigmoid sinus and internal carotid artery, were successfully reconstructed. The orientation of and spatial relationship among these structures were easily visualized in the reconstructed surface models. Conclusion The 3D Slicer software can be used for 3-dimensional visualization of anatomic structures in the temporal bone, which will greatly facilitate the advance of knowledge and techniques critical for studying and treating disorders involving the temporal bone.

  4. Gonadal dysgenesis and bone metabolism.

    Science.gov (United States)

    Breuil, V; Euller-Ziegler, L

    2001-02-01

    Gonadal dysgenesis is defined as congenital hypogonadism related to abnormalities of the sex chromosomes. Because sex steroids play a central role in the acquisition and maintenance of bone mass, studies have been done to investigate bone status in patients with gonadal dysgenesis, particularly Turner's syndrome and Klinefelter's syndrome, which are the two most common types. The severe estrogen deficiency characteristic of Turner's syndrome (44, X0) is associated with a significant bone mass decrease ascribable to increased bone turnover, as shown by histological studies and assays of bone turnover markers. Estrogen therapy is followed by a significant bone mass gain and a return to normal of bone turnover markers, suggesting that it is the estrogen deficiency rather than the chromosomal abnormality that causes the bone mass deficiency, although abnormalities in the renal metabolism of vitamin D have been reported. Combined therapy with estrogens and growth hormone seems beneficial during the prepubertal period. In Klinefelter's syndrome (47XXY), serum testosterone levels are at the lower end of the normal range and dihydrotestosterone levels are low. Histological studies show depressed osteoblast function and a decrease in 5-alpha-reductase activity responsible for partial tissue resistance to androgens. Assays of bone turnover markers show evidence of increased bone turnover. The bone deficiency is most marked at the femoral neck and seems correlated with serum testosterone and estradiol levels. Androgen therapy has favorable effects on the bone only if it is started before puberty. Recent data suggest that estrogens may contribute to the development of demineralization in KS and that bisphosphonate therapy may be beneficial.

  5. Bone biopsy (image)

    Science.gov (United States)

    A bone biopsy is performed by making a small incision into the skin. A biopsy needle retrieves a sample of bone and it ... examination. The most common reasons for bone lesion biopsy are to distinguish between benign and malignant bone ...

  6. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... needle is gently pushed and twisted into the bone. Once the sample is obtained, the needle is ... sample is sent to a lab for examination. Bone biopsy may also be done under general anesthesia ...

  7. Facts about Broken Bones

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? Broken Bones KidsHealth > For Kids > Broken Bones Print A A ... sticking through the skin . What Happens When a Bone Breaks? It hurts to break a bone! It's ...

  8. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  9. Broken Bones (For Parents)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Broken Bones KidsHealth > For Parents > Broken Bones Print A A ... bone fragments in place. When Will a Broken Bone Heal? Fractures heal at different rates, depending upon ...

  10. A generalized quantitative antibody homeostasis model: regulation of B-cell development by BCR saturation and novel insights into bone marrow function

    Science.gov (United States)

    Prechl, József

    2017-01-01

    In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this first paper, we describe the cycles of B-cell expansion and differentiation driven by B-cell receptor engagement. The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. We express BCR engagement as a function of apparent affinity and free antigen concentration, using the range of 10−14–10−3 M for both factors. We assume that for keeping their BCR responsive, B cells must maintain partial BCR saturation, which is a narrow region defined by [Ag]≈KD. To remain in this region, B cells respond to changes in [Ag] by proliferation or apoptosis and modulate KD by changing BCR structure. We apply this framework to various niches of B-cell development such as the bone marrow, blood, lymphoid follicles and germinal centers. We propose that clustered B cells in the bone marrow and in follicles present antigen to surrounding B cells by exposing antigen captured on complement and Fc receptors. The model suggests that antigen-dependent selection in the bone marrow results in (1) effector BI cells, which develop in blood as a consequence of the inexhaustible nature of soluble antigens, (2) memory cells that survive in antigen rich niches, identified as marginal zone B cells. Finally, the model implies that memory B cells could derive survival signals from abundant non-cognate antigens. PMID:28265373

  11. 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

  12. Adaptation of subchondral bone in osteoarthritis

    DEFF Research Database (Denmark)

    Ding, Ming

    2004-01-01

    never been proven. Recent studies showing reduced chemical and mechanical properties of subchondral bone in various stages of the disease have invigorated interest in the role of subchondral bone in the development and progression of the disease. The current study showed that the concept of bone...

  13. Suboccipital neuropathy after bone conduction device placement

    NARCIS (Netherlands)

    Faber, H.T.; Ru, J.A. de

    2013-01-01

    OBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed c

  14. Development of tailored and self-mineralizing citric acid-crosslinked hydrogels for in situ bone regeneration.

    Science.gov (United States)

    Sánchez-Ferrero, Aitor; Mata, Álvaro; Mateos-Timoneda, Miguel A; Rodríguez-Cabello, José C; Alonso, Matilde; Planell, Josep; Engel, Elisabeth

    2015-11-01

    Bone tissue engineering demands alternatives overcoming the limitations of traditional approaches in the context of a constantly aging global population. In the present study, elastin-like recombinamers hydrogels were produced by means of carbodiimide-catalyzed crosslinking with citric acid, a molecule suggested to be essential for bone nanostructure. By systematically studying the effect of the relative abundance of reactive species on gelation and hydrogel properties such as functional groups content, degradation and structure, we were able to understand and to control the crosslinking reaction to achieve hydrogels mimicking the fibrillary nature of the extracellular matrix. By studying the effect of polymer concentration on scaffold mechanical properties, we were able to produce hydrogels with a stiffness value of 36.13 ± 10.72 kPa, previously suggested to be osteoinductive. Microstructured and mechanically-tailored hydrogels supported the growth of human mesenchymal stem cells and led to higher osteopontin expression in comparison to their non-tailored counterparts. Additionally, tailored hydrogels were able to rapidly self-mineralize in biomimetic conditions, evidencing that citric acid was successfully used both as a crosslinker and a bioactive molecule providing polymers with calcium phosphate nucleation capacity.

  15. Engineers Create Bone that Blends into Tendons

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Engineers at Georgia Tech have used skin cells to create artificial bones that mimic the ability of natural bone to blend into other tissues such as tendons or ligaments. The artificial bones display a gradual change from bone to softer tissue rather than the sudden shift of previously developed artificial tissue, providing better integration with the body and allowing them to handle weight more successfully.

  16. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone...

  17. Effect of In-Ovo Ascorbic Acid Injection on the Bone Development of Broiler Chickens Submitted to Heat Stress During Incubation and Rearing

    Directory of Open Access Journals (Sweden)

    S Sgavioli

    2016-03-01

    Full Text Available Abstract This experiment was conducted to evaluate the effect of in-ovo ascorbic acid (AA injection on the bone development of broilers submitted to heat stress during incubation and rearing. One thousand (1,000 Cobb(rfertile broiler eggs were randomly distributed according to the weight into five incubators, with 200 eggs per incubator. The incubation treatments were: eggs not injected with AA and incubated at 37.5°C; eggs not injected with AA and incubated at 39°C; and eggs injected with 6 µg AA/100 µL water prior to incubation and incubated at 39ºC. The hatched birds were reared at three different house temperatures: cold, thermoneutral, or and hot. The high incubation temperature negatively influenced broilers' bone characteristics. The femur of the birds hatched from eggs incubated at 39°C and injected with AA presented lower shaft mineral density, lower maximum force and lower elongation at maximum force. Their tibia presented reduced mineral density at the proximal and distal epiphysis. In-ovo AA injection of eggs incubated at high temperature did not minimize the negative effects of high rearing temperature on the performance andbone development of broiler chickens reared until 42 days of age.

  18. Expression of GDF-5 during Limb Skeletal Development of Mice and the effect of GDF-5 on bone marrow mesenchymal stem cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Yukun Zhang; Shuhua Yang; Li Sun; Cao Yang; Zhewei Ye; Dehao Fu

    2006-01-01

    Objective: To investigate the expression of growth differentiation factor 5 (GDF-5) during limb skeletal development of mice and the effect of GDF-5 on bone marrow mesenchymal stem cells in vitro. Methods: The expression of GDF-5 mRNA and protein in mouse fetal limb buds were detected in embryonic day 11.5-15.5 (El1.5-15.5) by RT-PCR and Western blotting respectively. Type Ⅱ collagen protein was examined with immunocytochemistry and the sulfate glycosaminoglycan was measured by Alcian blue. Results: During early stage of developmental skeletogenesis, the expression of GDF-5mRNA was constant and began with embryos E11.5, highlighted at embryos E12.5 and E13.5, subsequently dropped at embryos E14.5 and E15.5.There was very significant difference (P < 0.01) in average light density ratio of GDF-5/β-actin between E12.5-13.5 and the other three days. The expression of GDF-5 protein had a similar change with mRNA during limb skeletogenesis. Immunocytochemistry showed that GDF-5 could promote expression of Type Ⅱ collagen protein and histological staining of proteoglycan with Alcian blue revealed the deposition of typical cartilage extracellular matrix components. Conclusion: GDF-5 can enhance chondrogenic differentiation of mouse bone marrow mesenchymal stem cells in vitro, which plays an important role in limb skeletal development and joint formation.

  19. Development and application of bone-anchored hearing aid%骨锚式助听器的发展及应用

    Institute of Scientific and Technical Information of China (English)

    刘宇鹏

    2013-01-01

    Bone-anchored hearing aid is a hearing assisting technology that raise the hearing level via bone conduct and is also the only implantable hearing assisting device working by bone conduct. Because of the superior performance and simple process of implantation, it brings gospel to the patients who are not fitting the air conducting hearing devices. This article is a review of bone-anchored hearing aid from 6 aspects, including history, principle, indication, consulting, surgery and complication.

  20. Development of efficient electron beam irradiating condition of artificial bone substitutes with 7 to 3 ratio of hydroxyapatite, tricalcium phosphate and type I collagen to maximize bony regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soung Min; Eo, Mi Young; Myoung, Hoon; Kang, Ji Young; Lee, Jong Ho [Seoul National Univ., Seoul (Korea, Republic of); Cho, Hye Jin [Korea Basic Science Institute, Daejeon (Korea, Republic of); Yea, Kwon Hae; Lee, Byungcheol [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-07-01

    Bony defects in oral and maxillofacial region was a common problem -Auto graft -Allograft -Xenograft. Accenting bone is 'Gold standard' for bone defect repair and from the rib, iliac crest, jaw and tibia. Bone is 70% inorganic components -which provide firmness, and approx. and 30% organic substances.

  1. Development of gelatin-chitosan-hydroxyapatite based bioactive bone scaffold with controlled pore size and mechanical strength.

    Science.gov (United States)

    Maji, Kanchan; Dasgupta, Sudip; Kundu, Biswanath; Bissoyi, Akalabya

    2015-01-01

    Hydroxyapatite-chitosan/gelatin (HA:Chi:Gel) nanocomposite scaffold has potential to serve as a template matrix to regenerate extra cellular matrix of human bone. Scaffolds with varying composition of hydroxyapatite, chitosan, and gelatin were prepared using lyophilization technique where glutaraldehyde (GTA) acted as a cross-linking agent for biopolymers. First, phase pure hydroxyapatite-chitosan nanocrystals were in situ synthesized by coprecipitation method using a solution of 2% acetic acid dissolved chitosan and aqueous solution of calcium nitrate tetrahydrate [Ca(NO3)2,4H2O] and diammonium hydrogen phosphate [(NH4)2H PO4]. Keeping solid loading constant at 30 wt% and changing the composition of the original slurry of gelatin, HA-chitosan allowed control of the pore size, its distribution, and mechanical properties of the scaffolds. Microstructural investigation by scanning electron microscopy revealed the formation of a well interconnected porous scaffold with a pore size in the range of 35-150 μm. The HA granules were uniformly dispersed in the gelatin-chitosan network. An optimal composition in terms of pore size and mechanical properties was obtained from the scaffold with an HA:Chi:Gel ratio of 21:49:30. The composite scaffold having 70% porosity with pore size distribution of 35-150 μm exhibited a compressive strength of 3.3-3.5 MPa, which is within the range of that exhibited by cancellous bone. The bioactivity of the scaffold was evaluated after conducting mesenchymal stem cell (MSC) - materials interaction and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay using MSCs. The scaffold found to be conducive to MSC's adhesion as evident from lamellipodia, filopodia extensions from cell cytoskeleton, proliferation, and differentiation up to 14 days of cell culture.

  2. Development of superior bone scintigraphic agent from a series of {sup 99m}Tc-labeled zoledronic acid derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jianguo [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Qiu Ling, E-mail: qiulingwx@gmail.com [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Cheng Wen [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Luo Shineng, E-mail: shineng914@yahoo.com.cn [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Xue Li; Zhang Shu [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China)

    2012-05-15

    Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6 h post preparation. Their in vivo biological performances were evaluated and compared with those of {sup 99m}Tc-ZL and {sup 99m}Tc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent {sup 99m}Tc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that {sup 99m}Tc-IPeDP would be a novel superior bone scintigraphic agent. - Highlights: Black-Right-Pointing-Pointer Two novel diphosphonic acids were labeled with the {sup 99m}Tc in high labeling yield. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP had high uptake in skeletal system and rapid clearance from blood. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP reveals attractive biological features as superior bone scanning agent.

  3. Swimming training repercussion on metabolic and structural bone development: benefits of the incorporation of whole body vibration or pilometric training; the RENACIMIENTO project

    Directory of Open Access Journals (Sweden)

    A. Gómez-Bruton

    2014-08-01

    Full Text Available Introduction: Enviromental factors such as exercise participation and nutrition have often been linked to bone improvements. However, not all sports have the same effects, being non-osteogenic sports such as swimming defined as negative or neutral sports to practice regarding bone mass by some authors, similarly exercise-diet interaction in especific groups is still not clear. Objective: To present the methodology of the RENACIMENTO project that aims to evaluate body composition and more specifically bone mass by several techniques in adolescent swimmers and to observe the effects and perdurability of whole body vibration (WBV and jumping intervention (JIN on body composition and fitness on this population and explore posible diet interactions. Design: Randomized controlled trial. Methods: 78 swimmers (12-17 y and 26 sex- and age-matched controls will participate in this study. Dual energy X-ray, peripheral Quantitative Computed Tomography, Quantitative Ultrasound, Bioelectrical Impedance Analysis, and anthropometry measurements will be performed in order to evaluate body composition. Physical activity, nutrition, pubertal development and socio-economical status may act as confounders of body composition and therefore will also be registered. Several fitness factors regarding strength, endurance, performance and others will also be registered to evaluate differences with controls and act as confounders. A 7-month WBV therapy will be performed by 26 swimmers consisting of a training of 15 minutes 3 times per week. An 8 month JIM will also be performed by 26 swimmers 3 times per week. The remaining 26 swimmers will continue their normal swimming training. Four evaluations will be performed, the first one in order to describe differences between swimmers and controls. The second one to describe the effects of the interventions and the third and fourth evaluations to describe the perdurability of the effects of the WBV and JIN. Conclusion: The

  4. Development of Bone-Conducted Ultrasonic Hearing Aid for the Profoundly Deaf: Assessments of the Modulation Type with Regard to Intelligibility and Sound Quality

    Science.gov (United States)

    Nakagawa, Seiji; Fujiyuki, Chika; Kagomiya, Takayuki

    2012-07-01

    Bone-conducted ultrasound (BCU) is perceived even by the profoundly sensorineural deaf. A novel hearing aid using the perception of amplitude-modulated BCU (BCU hearing aid: BCUHA) has been developed; however, further improvements are needed, especially in terms of articulation and sound quality. In this study, the intelligibility and sound quality of BCU speech with several types of amplitude modulation [double-sideband with transmitted carrier (DSB-TC), double-sideband with suppressed carrier (DSB-SC), and transposed modulation] were evaluated. The results showed that DSB-TC and transposed speech were more intelligible than DSB-SC speech, and transposed speech was closer than the other types of BCU speech to air-conducted speech in terms of sound quality. These results provide useful information for further development of the BCUHA.

  5. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth.

  6. [Bone disease in Gaucher's disease].

    Science.gov (United States)

    Roca Espiau, Mercedes

    2011-09-01

    The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

  7. Putative Role Of Fgf 23 In The Development Of Hypophosphatemia And Bone Fructures In An Anemic Patient Treated By Intravenous Saccharated Ferric Oxide

    Directory of Open Access Journals (Sweden)

    Risa Ishida

    2012-06-01

    Full Text Available A post-menopausal patient with normal kidney function was referred to our hospital because of severe lumber pain. She had been treated by initially oral, and then by intravenous iron for longer than five years for the treatment of iron deficiency anemia due to recurrent GI bleeding. On admission, multiple lumber bone fracture with low bone mineral density was confirmed. Laboratory tests revealed severe hypophosphatemia (1.6 mg/dl with slight decrease of calcium ion level. Serum levels of 25D and 1,25D were low normal, while increase of intact PTH (83.9 pg/ml and FGF23 (60 pg/ml were observed. After terminating intravenous iron supplement, her symptoms and hypophsophatemia were gradually normalized with oral active vitamin D treatment. Although we could not completely exclude the contribution of disturbed iron absorption from the intestine, damages of proximal tubular cells by iron, and osteomalacia caused by the deposition of iron, increased FGF23 level may have played critical roles in the development of severe hypophosphatemia in this patient. Such hypophosphatemia due to high FGF23 has recently been reported in patients treated by intravenous sacharated ferric oxide.

  8. 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)

  9. Increased IL-6 Expression in Osteoclasts Is Necessary But Not Sufficient for the Development of Paget’s Disease of Bone

    Science.gov (United States)

    Teramachi, Jumpei; Zhou, Hua; Subler, Mark A; Kitagawa, Yukiko; Galson, Deborah L; Dempster, David W; Windle, Jolene J; Kurihara, Noriyoshi; Roodman, G David

    2015-01-01

    Measles virus nucleocapsid protein (MVNP) expression in osteoclasts (OCLs) and mutation of the SQSTM1 (p62) gene contribute to the increased OCL activity in Paget’s disease (PD). OCLs expressing MVNP display many of the features of PD OCLs. Interleukin-6 (IL-6) production is essential for the pagetic phenotype, because transgenic mice with MVNP targeted to OCLs develop pagetic OCLs and lesions, but this phenotype is absent when MVNP mice are bred to IL-6−/− mice. In contrast, mutant p62 expression in OCL precursors promotes receptor activator of NF-κB ligand (RANKL) hyperresponsivity and increased OCL production, but OCLs that form have normal morphology, are not hyperresponsive to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), nor produce elevated levels of IL-6. We previously generated p62P394L knock-in mice (p62KI) and found that although OCL numbers were increased, the mice did not develop pagetic lesions. However, mice expressing both MVNP and p62KI developed more exuberant pagetic lesions than mice expressing MVNP alone. To examine the role of elevated IL-6 in PD and determine if MVNP mediates its effects primarily through elevation of IL-6, we generated transgenic mice that overexpress IL-6 driven by the tartrate-resistant acid phosphatase (TRAP) promoter (TIL-6 mice) and produce IL-6 at levels comparable to MVNP mice. These were crossed with p62KI mice to determine whether IL-6 overexpression cooperates with mutant p62 to produce pagetic lesions. OCL precursors from p62KI/TIL-6 mice formed greater numbers of OCLs than either p62KI or TIL-6 OCL precursors in response to 1,25-(OH)2D3. Histomorphometric analysis of bones from p62KI/TIL-6 mice revealed increased OCL numbers per bone surface area compared to wild-type (WT) mice. However, micro-quantitative CT (μQCT) analysis did not reveal significant differences between p62KI/TIL-6 and WT mice, and no pagetic OCLs or lesions were detected in vivo. Thus, increased IL-6 expression in OCLs from p62KI mice

  10. Bone Circulatory Disturbances in the Development of Spontaneous Bacterial Chondronecrosis with Osteomyelitis: A Translational Model for the Pathogenesis of Femoral Head Necrosis

    Directory of Open Access Journals (Sweden)

    Robert F. Wideman

    2013-01-01

    Full Text Available This review provides a comprehensive overview of the vascularization of the avian growth plate and its subsequent role in the pathogenesis of bacterial chondronecrosis with osteomyelitis (BCO, femoral head necrosis. BCO sporadically causes high incidences of lameness in rapidly growing broiler (meat-type chickens. BCO is believed to be initiated by micro-trauma to poorly mineralized columns of cartilage cells in the proximal growth plates of the leg bones, followed by colonization by hematogenously distributed opportunistic bacteria. Inadequate blood flow to the growth plate, vascular occlusion, and structural limitations of the microvasculature all have been implicated in the pathogenesis of BCO. Treatment strategies have been difficult to investigate because under normal conditions the incidence of BCO typically is low and sporadic. Rearing broilers on wire flooring triggers the spontaneous development of high incidences of lameness attributable to pathognomonic BCO lesions. Wire flooring imposes persistent footing instability and is thought to accelerate the development of BCO by amplifying the torque and shear stress imposed on susceptible leg joints. Wire flooring per se also constitutes a significant chronic stressor that promotes bacterial proliferation attributed to stress-mediated immunosuppression. Indeed, dexamethasone-mediated immunosuppression causes broilers to develop lameness primarily associated with avascular necrosis and BCO. Prophylactic probiotic administration consistently reduces the incidence of lameness in broilers reared on wire flooring, presumably by reducing bacterial translocation from the gastrointestinal tract that likely contributes to hematogenous infection of the leg bones. The pathogenesis of BCO in broilers is directly relevant to osteomyelitis in growing children, as well as to avascular femoral head necrosis in adults. Our new model for reliably triggering spontaneous osteomyelitis in large numbers of

  11. Double expression of CD34 and CD117 on bone marrow progenitors is a hallmark of the development of functional mast cell of Callithrix jacchus (common marmoset).

    Science.gov (United States)

    Nunomura, Satoshi; Shimada, Shin; Kametani, Yoshie; Yamada, Yuko; Yoshioka, Mino; Suemizu, Hiroshi; Ozawa, Manabu; Itoh, Toshio; Kono, Azumi; Suzuki, Ryuji; Tani, Kenzaburo; Ando, Kiyoshi; Yagita, Hideo; Ra, Chisei; Habu, Sonoko; Satake, Masanobu; Sasaki, Erika

    2012-09-01

    Mast cells (MCs) are developed from hematopoietic progenitor cells and play an important role in inflammation. Study of the kinetics of development and accumulation of primate MC in vivo is crucial for the control of human inflammatory diseases, as evolution of the immune system is quite rapid and inflammation including MC response is considered to be different between mouse and human. In the present study, we examined the development of MC from hematopoietic progenitors of Callithrix jacchus (common marmoset), an experimental animal of nonhuman primates. Bone marrow cells were fractionated for the expression of CD34 and CD117 by cell sorting. MCs were developed in vitro or by transplanting the cells to NOD/SCID/IL-2γc knockout (NOG) mice. In vitro culture of CD34(+)CD117(+) (double positive, DP) cells with stem cell factor could generate high-affinity Fc epsilon receptor (FcεR)-expressing CD117(+) cells with typical granules. The developed MC released β-hexosaminidase and produced leukotriene C(4) after the stimulation of FcεRI. Transplantation of DP cells gave rise to a marked expansion of CD34(-)CD45(+)CD117(+)FcεR(+) cells in NOG mice. They expressed transcripts encoding chymase 1 and tryptase β. Differentiation of CD34(-)CD117(+) cells to MCs was relatively limited compared with the DP cells, similarly to human MCs. These results suggest that this marmoset system provides a good model for human MC development.

  12. Brown fat determination and development from muscle precursor cells by novel action of bone morphogenetic protein 6.

    Directory of Open Access Journals (Sweden)

    Ankur Sharma

    Full Text Available Brown adipose tissue (BAT plays a pivotal role in promoting energy expenditure by the virtue of uncoupling protein-1 (UCP-1 that differentiates BAT from its energy storing white adipose tissue (WAT counterpart. The clinical implication of "classical" BAT (originates from Myf5 positive myoblastic lineage or the "beige" fat (originates through trans-differentiation of WAT activation in improving metabolic parameters is now becoming apparent. However, the inducers and endogenous molecular determinants that govern the lineage commitment and differentiation of classical BAT remain obscure. We report here that in the absence of any forced gene expression, stimulation with bone morphogenetic protein 6 (BMP6 induces brown fat differentiation from skeletal muscle precursor cells of murine and human origins. Through a comprehensive transcriptional profiling approach, we have discovered that two days of BMP6 stimulation in C2C12 myoblast cells is sufficient to induce genes characteristic of brown preadipocytes. This developmental switch is modulated in part by newly identified regulators, Optineurin (Optn and Cyclooxygenase-2 (Cox2. Furthermore, pathway analyses using the Causal Reasoning Engine (CRE identified additional potential causal drivers of this BMP6 induced commitment switch. Subsequent analyses to decipher key pathway that facilitates terminal differentiation of these BMP6 primed cells identified a key role for Insulin Like Growth Factor-1 Receptor (IGF-1R. Collectively these data highlight a therapeutically innovative role for BMP6 by providing a means to enhance the amount of myogenic lineage derived brown fat.

  13. Dating of cremated bones

    NARCIS (Netherlands)

    Lanting, JN; Aerts-Bijma, AT; van der Plicht, J; Boaretto, E.; Carmi, I.

    2001-01-01

    When dating unburnt bone, bone collagen, the organic fraction of the bone, is used. Collagen does not survive the heat of the cremation pyre, so dating of cremated bone has been considered impossible. Structural carbonate in the mineral fraction of the bone, however, survives the cremation process.

  14. Development of conjugated estrogens/bazedoxifene, the first tissue selective estrogen complex (TSEC) for management of menopausal hot flashes and postmenopausal bone loss.

    Science.gov (United States)

    Komm, Barry S; Mirkin, Sebastian; Jenkins, Simon N

    2014-11-01

    Conjugated estrogens (CE) combined with the selective estrogen receptor modulator (SERM) bazedoxifene (BZA) is a new option for alleviating menopausal symptoms and preventing postmenopausal bone loss. The rationale for developing the tissue selective estrogen complex (TSEC) CE/BZA was to combine CE's benefits with the SERM's tissue-specific properties to offset estrogenic stimulation of endometrial and breast tissue. TSECs provide a progestin-free alternative to traditional estrogen-progestin therapy (EPT) in women with a uterus. Preclinical studies supported bazedoxifene as the SERM of choice and demonstrated that CE/BZA provided an optimal balance of estrogen receptor agonist/antagonist activity compared with other potential TSEC pairings. Initial clinical development of CE/BZA focused on determining the appropriate dose ratio that would demonstrate efficacy with minimal to no stimulation of the breast or endometrium. Clinical studies confirmed the efficacy of the selected doses for maintaining bone mass; relieving vasomotor symptoms, vulvar-vaginal atrophy, and dyspareunia; and improving sexual function in postmenopausal women. Reduction of hot flashes also translated into improved menopause-specific quality of life and sleep. Unlike EPT, the FDA-approved dose of CE 0.45 mg/BZA 20mg does not cause a change in breast density or the endometrium, or increase breast pain compared with placebo. In clinical trials up to 2 years, CE 0.45 mg/BZA 20 mg has a favorable tolerability profile and rates of coronary heart disease, venous thromboembolism, and amenorrhea similar to placebo. Therefore, CE 0.45 mg/BZA 20 mg is an effective, well-tolerated alternative to EPT for menopausal symptom relief and osteoporosis prevention for postmenopausal women with a uterus.

  15. Smoking and Bone Health

    Science.gov (United States)

    ... supported by your browser. Home Bone Basics Lifestyle Smoking and Bone Health Publication available in: PDF (85 ... late to adopt new habits for healthy bones. Smoking and Osteoporosis Cigarette smoking was first identified as ...

  16. Vitamin D -prevalence, mortality and bone pain

    DEFF Research Database (Denmark)

    Durup, Darshana Tiffany

    2013-01-01

    Bone pain is a common and debilitating symptom of many metabolic bone diseases. However, almost nothing is known about the molecular and cellular mechanisms leading to bone pain and the pain states are poorly characterized. It is well-established that osteomalacia due to severe vitamin D deficiency...... of this thesis was to determine the prevalence of vitamin D insufficiency and deficiency and its impact on mortality. Furthermore, a multidisciplinary and translational study was carried out to investigate the effects of disturbed calcified tissue on the nervous system. Thus, quantification and characterization...... of the pain syndrome in patients with vitamin D deficiency and bone pain. Furtherme, development of a non-cancer animal model of bone pain, was carried out, to enable investigations of bone pain threshold, bone microenvironment and endocrinology parameters involved in this debilitating disease. A unique...

  17. Findings of skin and bones in mastocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Rohner, H.G.; Bartl, R.; Koischwitz, D.; Rodermund, O.E.

    1982-12-01

    The syndrome of mastocytosis can include isolated urticaria pigmentosa, systemic mastocytosis, or the extremely rare form of mast cell leucemia. Our investigations of many patients have shown more frequently than earlier suspected, that the mastocytosis is a systemic disease. The frequency of attacked bone marrow is noteworthy. Because of the inflammatory granulomatous manifestation in bone marrow, considerations of the pathogenesis of an immune and reactive event are taken into account. The mast cell granulomas are mostly found in the endosteal region, which is the reason for frequently occurring bone lesions (half of all patients show bone lesions). The bone changes can develop generalized (osteoporosis-osteosclerosis) or localized (osteolytic-osteosclerotic foci). In clinical work bone biopsies and skeletal radiology are supplementing each other: bone biopsy and skin biopsy give the first diagnosis of mastocytosis and reveal the systemic disease; X-ray pictures give information of shape and dimension of the induced osteopathy.

  18. Mechanisms of multiple myeloma bone disease

    Science.gov (United States)

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

    2012-01-01

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

  19. 3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair.

    Science.gov (United States)

    Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong

    2014-09-10

    The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

  20. New regenerative treatment for tooth and periodontal bone defect associated with posttraumatic alveolar bone crush fracture.

    Science.gov (United States)

    Kiyokawa, Kensuke; Kiyokawa, Munekatsu; Takagi, Mikako; Rikimaru, Hideaki; Fukaya, Takuji

    2009-05-01

    We developed a new regenerative treatment of tooth and periodontal defect and tooth dislocation associated with posttraumatic alveolar bone crush fracture in the region of the maxillary anterior teeth. Using this method, dislocated teeth are first extracted and crushed alveolar bone is debrided. The dislocated teeth are then reimplanted, and cancellous iliac bone (bone marrow) is grafted to the area surrounding the teeth to regenerate periodontal bone. Tooth reimplantation was completely successful in 2 cases, and periodontal bone regenerated to a sufficient height with the iliac bone graft. Compared with the general method of treatment with a prosthesis (bridge), when using this method to treat cases such as these, there is no sacrifice of healthy teeth adjacent to the defect, and sufficient esthetic and functional recovery is possible. It is thought that this method could be applied as a new treatment of alveolar bone fracture in the future.

  1. Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

    Science.gov (United States)

    Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

    2014-02-01

    The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases.

  2. Bone health in disorders of sex differentiation.

    Science.gov (United States)

    Bertelloni, S; Baroncelli, G I; Mora, S

    2010-09-01

    Sex steroids are main regulators of skeletal growth, maturation and mass in both men and women. People with disorders of sex development (DSD) may experience problems in developing normal bone growth, structure and mass, because abnormal sex steroid secretion or action may be operative. In complete androgen insensitivity syndrome several reports documented reduced bone mineral density (BMD). Reduced BMD is evident in patients with not removed or removed gonads, but it is poorer in the latter, mainly when compliance with estrogen replacement therapy is not guaranteed. Large impairment of BMD does not seem to be present in patients with partial androgen insensitivity syndrome or 5alpha-reductase-2 deficiency, providing that gonads are not removed or that substitutive therapy is optimized. In congenital adrenal hyperplasia, BMD may be impaired as a result of not optimal glucocorticoid administration. In Turner syndrome, impaired BMD may result from the combined actions of estrogen deficiency, low bone dimensions, altered bone geometry, deficient cortical bone, and trabecular bone loss. Optimal estrogen administration seems to be important in preserving bone mass and enhancing trabecular bone volume. On the whole, bone health represents a main clinical issue for the management of persons with disorders of sex differentiation, and well designed longitudinal studies should be developed to improve their bone health and well-being.

  3. Bone remodeling as a spatial evolutionary game.

    Science.gov (United States)

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

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

  4. Interleukin-32 Gamma Stimulates Bone Formation by Increasing miR-29a in Osteoblastic Cells and Prevents the Development of Osteoporosis

    Science.gov (United States)

    Lee, Eun-Jin; Kim, Sang-Min; Choi, Bongkun; Kim, Eun-Young; Chung, Yeon-Ho; Lee, Eun-Ju; Yoo, Bin; Lee, Chang-Keun; Hong, Seokchan; Kim, Beom-Jun; Koh, Jung-Min; Kim, Soo-Hyun; Kim, Yong-Gil; Chang, Eun-Ju

    2017-01-01

    Interleukin-32 gamma (IL-32γ) is a recently discovered cytokine that is elevated in inflamed tissues and contributes to pathogenic features of bone in human inflammatory rheumatic diseases. Nevertheless, the role of IL-32γ and its direct involvement in bone metabolism is unclear. We investigated the molecular mechanism of IL-32γ in bone remodeling and the hypothetical correlation between IL-32γ and disease activity in osteoporosis patients. Transgenic (TG) mice overexpressing human IL-32γ showed reduced bone loss with advancing age, increased bone formation, and high osteogenic capacity of osteoblast compared to wild-type (WT) mice through the upregulation of miR-29a, which caused a reduction of Dickkopf-1 (DKK1) expression. IL-32γ TG mice were protected against ovariectomy (OVX)induced osteoporosis compared with WT mice. Decreased plasma IL-32γ levels were associated with bone mineral density (BMD) in human patients linked to increased DKK1 levels. These results indicate that IL-32γ plays a protective role for bone loss, providing clinical evidence of a negative correlation between IL-32γ and DKK1 as bone metabolic markers. PMID:28079119

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

    Science.gov (United States)

    Hambli, Ridha

    2014-01-01

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

  6. Bone balance within a cortical BMU: local controls of bone resorption and formation.

    Directory of Open Access Journals (Sweden)

    David W Smith

    Full Text Available Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the 'integration of information' occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable

  7. Bone balance within a cortical BMU: local controls of bone resorption and formation.

    Science.gov (United States)

    Smith, David W; Gardiner, Bruce S; Dunstan, Colin

    2012-01-01

    Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the 'integration of information' occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors.

  8. Three-dimensional microarchitecture of adolescent cancellous bone

    DEFF Research Database (Denmark)

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

    2012-01-01

    This study investigated microarchitectural, mechanical, collagen and mineral properties of normal adolescent cancellous bone, and compared them with adult and aging cancellous bone, to obtain more insight into the subchondral bone adaptations during development and growth. Twenty-three human...... proximal tibiae were harvested and divided into 3 groups according to their ages: adolescence (9 to 17years, n=6), young adult (18 to 24years, n=9), and adult (25 to 30years, n=8). Twelve cubic cancellous bone samples with dimensions of 8×8×8mm(3) were produced from each tibia, 6 from each medial......, the adolescent cancellous bone had similar bone volume fraction (BV/TV), structure type (plate, rod or mixtures), and connectivity (3-D trabecular networks) as the adult cancellous bone. The adolescent cancellous bone had significantly lower bone surface density (bone surface per total volume of specimen...

  9. [Fractures of carpal bones].

    Science.gov (United States)

    Lögters, T; Windolf, J

    2016-10-01

    Fractures of the carpal bones are uncommon. On standard radiographs fractures are often not recognized and a computed tomography (CT) scan is the diagnostic method of choice. The aim of treatment is to restore pain-free and full functioning of the hand. A distinction is made between stable and unstable carpal fractures. Stable non-displaced fractures can be treated conservatively. Unstable and displaced fractures have an increased risk of arthritis and non-union and should be stabilized by screws or k‑wires. If treated adequately, fractures of the carpal bones have a good prognosis. Unstable and dislocated fractures have an increased risk for non-union. The subsequent development of carpal collapse with arthrosis is a severe consequence of non-union, which has a heterogeneous prognosis.

  10. Vitamin D and Bone Disease

    Directory of Open Access Journals (Sweden)

    S. Christodoulou

    2013-01-01

    Full Text Available Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a “good bone health” guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.

  11. Bone tissue engineering: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Maria A. Woodruff

    2012-10-01

    Full Text Available The drive to develop bone grafts for the filling of major gaps in the skeletal structure has led to a major research thrust towards developing biomaterials for bone engineering. Unfortunately, from a clinical perspective, the promise of bone tissue engineering which was so vibrant a decade ago has so far failed to deliver the anticipated results of becoming a routine therapeutic application in reconstructive surgery. Here we describe our bench to bedside concept, the first clinical results and a detailed analysis of long-term bone regeneration studies in preclinical animal models, exploiting methods of micro- and nano analysis of biodegradable composite scaffolds.

  12. High-strength mineralized collagen artificial bone

    Science.gov (United States)

    Qiu, Zhi-Ye; Tao, Chun-Sheng; Cui, Helen; Wang, Chang-Ming; Cui, Fu-Zhai

    2014-03-01

    Mineralized collagen (MC) is a biomimetic material that mimics natural bone matrix in terms of both chemical composition and microstructure. The biomimetic MC possesses good biocompatibility and osteogenic activity, and is capable of guiding bone regeneration as being used for bone defect repair. However, mechanical strength of existing MC artificial bone is too low to provide effective support at human load-bearing sites, so it can only be used for the repair at non-load-bearing sites, such as bone defect filling, bone graft augmentation, and so on. In the present study, a high strength MC artificial bone material was developed by using collagen as the template for the biomimetic mineralization of the calcium phosphate, and then followed by a cold compression molding process with a certain pressure. The appearance and density of the dense MC were similar to those of natural cortical bone, and the phase composition was in conformity with that of animal's cortical bone demonstrated by XRD. Mechanical properties were tested and results showed that the compressive strength was comparable to human cortical bone, while the compressive modulus was as low as human cancellous bone. Such high strength was able to provide effective mechanical support for bone defect repair at human load-bearing sites, and the low compressive modulus can help avoid stress shielding in the application of bone regeneration. Both in vitro cell experiments and in vivo implantation assay demonstrated good biocompatibility of the material, and in vivo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load-bearing sites.

  13. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Directory of Open Access Journals (Sweden)

    Ye Li

    2015-07-01

    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  14. Comparison of expression patterns of fibroblast growth factor 8, bone morphogenetic protein 4 and sonic hedgehog in jaw development of the house shrew, Suncus murinus.

    Science.gov (United States)

    Ogi, Hidenao; Tabata, Makoto J; Yamanaka, Atsushi; Yasui, Kinya; Uemura, Masanori

    2002-01-01

    To elucidate the mechanism underlying jaw development in mammals, we used a new laboratory animal, Suncus murinus (house shrew, an insectivore) as the subject for the investigation, because Suncus has all types of teeth (incisor, canine, premolar and molar) in its upper and lower jaws and is thought to be a good model animal having a general mammalian tooth pattern. At the start, by use of degenerate primers we cloned Suncus homologues of fibroblast growth factor 8 (sFgf8), bone morphogenetic protein 4 (sBmp4) and sonic hedgehog (sShh) genes from cDNA library derived from whole Suncus embryos at day 12 (E12). Thereafter, we examined the expression patterns of these genes in the jaw development of Suncus E11-16 embryos (for mouse E9.5-12 embryos). sFgf8 and sBmp4 were expressed in E11 but not in E15 and onward during orofacial development. sShh was expressed from E11 onward, and its expression was increased in the orofacial area. The expression pattern of sFgf8 in the maxillary and mandibular arches of E14 coincided with the area of the presumptive tooth arch. However, sShh and sBmp4 were expressed only in the outer area (= buccal/labial side) of presumptive tooth arch. Thus, these 3 genes showed specific expression pattern in jaw development of Suncus, and their distributions did not overlap each other except in a few regions. These findings suggest that sFgf8, sBmp4 and sShh have a specific function respectively during jaw development in Suncus murinus.

  15. Development of a Food Group-Based Diet Score and Its Association with Bone Mineral Density in the Elderly: The Rotterdam Study

    Directory of Open Access Journals (Sweden)

    Ester A.L. de Jonge

    2015-08-01

    Full Text Available No diet score exists that summarizes the features of a diet that is optimal for bone mineral density (BMD in the elderly. Our aims were (a to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature, and (b to examine the association of the BMD-Diet Score and the Healthy Diet Indicator, a score based on guidelines of the World Health Organization, with BMD in Dutch elderly participating in a prospective cohort study, the Rotterdam Study (n = 5144. Baseline dietary intake, assessed using a food frequency questionnaire, was categorized into food groups. Food groups that were consistently associated with BMD in the literature were included in the BMD-Diet Score. BMD was measured repeatedly and was assessed using dual energy X-ray absorptiometry. The BMD-Diet Score considered intake of vegetables, fruits, fish, whole grains, legumes/beans and dairy products as “high-BMD” components and meat and confectionary as “low-BMD” components. After adjustment, the BMD-Diet Score was positively associated with BMD (β (95% confidence interval = 0.009 (0.005, 0.012 g/cm2 per standard deviation. This effect size was approximately three times as large as has been observed for the Healthy Diet Indicator. The food groups included in our BMD-Diet Score could be considered in the development of future dietary guidelines for healthy ageing.

  16. Development of a Bone-Conducted Ultrasonic Hearing Aid for the Profoundly Deaf: Evaluation of Sound Quality Using a Semantic Differential Method

    Science.gov (United States)

    Nakagawa, Seiji; Fujiyuki, Chika; Kagomiya, Takayuki

    2013-07-01

    Bone-conducted ultrasound (BCU) is perceived even by the profoundly sensorineural deaf. A novel hearing aid using the perception of amplitude-modulated BCU (BCU hearing aid: BCUHA) has been developed. However, there is room for improvement particularly in terms of sound quality. BCU speech is accompanied by a strong high-pitched tone and contain some distortion. In this study, the sound quality of BCU speech with several types of amplitude modulation [double-sideband with transmitted carrier (DSB-TC), double-sideband with suppressed carrier (DSB-SC), and transposed modulations] and air-conducted (AC) speech was quantitatively evaluated using semantic differential and factor analysis. The results showed that all the types of BCU speech had higher metallic and lower esthetic factor scores than AC speech. On the other hand, transposed speech was closer than the other types of BCU speech to AC speech generally; the transposed speech showed a higher powerfulness factor score than the other types of BCU speech and a higher esthetic factor score than DSB-SC speech. These results provide useful information for further development of the BCUHA.

  17. Investigating the interaction between hematopoietic stem cells and their niche during embryonic development: optimizing the isolation of fetal and newborn stem cells from liver, spleen, and bone marrow.

    Science.gov (United States)

    Cao, Huimin; Williams, Brenda; Nilsson, Susan K

    2014-01-01

    Hematopoietic stem cells (HSCs) are maintained in a particular microenvironment termed a "niche." Within the niche, a number of critical molecules and supportive cell types have been identified to play key roles in modulating adult HSC quiescence, proliferation, differentiation, and reconstitution. However, unlike in the adult bone marrow (BM), the components of stem cell niches, as well as their interactions with fetal HSC during different stages of embryonic development, are poorly understood. During embryogenesis, hematopoietic development migrates through multiple organs, each with different cellular and molecular components and hence each with a potentially unique HSC niche. As a consequence, isolating fetal HSC from each organ at the time of hematopoietic colonization is fundamental for assessing and understanding both HSC function and their interactions with specific microenvironments. Herein, we describe methodologies for harvesting cells as well as the purification of stem and progenitors from fetal and newborn liver, spleen, and BM at various developmental stages following the expansion of hematopoiesis in the fetal liver at E14.5.

  18. 骨肿瘤的发生发展及转移%The occurrence,development and metastasis in bone neoplasms

    Institute of Scientific and Technical Information of China (English)

    杨澄; 苏宏伟; 任慧文; 李宏伟

    2014-01-01

    Bonetumorisonekindofmalignanttumorwhichthreatslifeamongchildrenandadoles-cent.Osteosarcoma (OS ) and Ewing sarcoma (ES ) have been paid much attention by medical community because of their complex occurrence,development,metastasis mechanism and poor prognosis.The research showed that activation of protooncogene and mutation of suppressor gene,absence of apoptosis signal and hypox-ia-inducible factor (HIF)all participated in the occurrence,development and metastasis of OS and ES.It is suggested that clarified pathomechanism of bone tumors could provide more effective therapeutic strategies and lower the mortality of patients.%骨肿瘤中骨肉瘤(OS)和尤文肉瘤(ES)因具有较复杂的发生、发展、转移机制和不良预后而受到医学界的广泛关注。研究表明原癌基因的激活和抑癌基因的突变、凋亡信号缺失和乏氧诱导因子等均参与OS和ES的发生、发展及转移。阐明骨肿瘤复杂的病理机制能为OS和ES提供更有效的靶向治疗手段和降低患者的死亡率。

  19. An in vitro approach to evaluate and develop potential Sn-117m based bone-seeking radiopharmaceuticals

    NARCIS (Netherlands)

    Jansen, D.R.

    2010-01-01

    It has become standard practice in the development of radiopharmaceuticals to evaluate/assess the efficacy of prospective therapeutic or diagnostic agents by animal models, which generally calls for subjecting a substantial number of animals to intensive test and retest measurements for obtaining re

  20. Impact of lanthanum carbonate on cortical bone in dialysis patients with adynamic bone disease.

    Science.gov (United States)

    Yajima, Aiji; Inaba, Masaaki; Tominaga, Yoshihiro; Tanaka, Motoko; Otsubo, Shigeru; Nitta, Kosaku; Ito, Akemi; Satoh, Shigeru

    2013-04-01

    Among the most serious problems in patients with chronic kidney disease (CKD) is fragility of cortical bone caused by cortical thinning and increased cortical porosity; the cortical fragility is sometimes irreversible, with fractures generally initiating from cortical bone. Therefore, development of treatments for problems of cortical bone is urgently desired. Cortical bone has the three surfaces, including the periosteal surface, intracortical spaces and endocortical surface. Bone turnover at the endocortical surface and intracortical resorption spaces are increased as compared with that at cancellous surface. Bone growth sometimes depends on apposition at the periosteal surface. We treated hyperphosphatemia in two hemodialysis patients with adynamic bone disease with 750-1500 mg/day of lanthanum carbonate, which is a non-calcium containing phosphate binder; the treatment resulted in a decrease of the serum phosphorus levels (P levels), without significant change of the serum intact parathyroid hormone levels. We now report that treatment of these patients with lanthanum carbonate increased mineralization of the periosteal surface, increased bone mass within the intracortical resorption spaces and increased mineralization of the minimodeling surface at the endocortical surface. In addition, woven bone volume in cortical bone was decreased and mineralization of bone units, namely, osteons, was increased. Although these findings were not observed across all surfaces of the cortical bone in the patients, it is expected that lanthanum carbonate would increase the cortical stability in CKD patients, with consequent reduction in the fracture rate in these patients.

  1. Orchestration of bone remodeling

    NARCIS (Netherlands)

    Moester, Martiene Johanna Catharina

    2014-01-01

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

  2. 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.

  3. Bone Marrow Diseases

    Science.gov (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  4. Cannabinoids and bone: friend or foe?

    Science.gov (United States)

    Idris, Aymen I; Ralston, Stuart H

    2010-10-01

    The endocannabinoid system is recognized to play an important role in regulating a variety of physiological processes, including appetite control and energy balance, pain perception, and immune responses. The endocannabinoid system has also recently been implicated in the regulation of bone metabolism. Endogenously produced cannabinoids are hydrophobic molecules derived from hydrolysis of membrane phospholipids. These substances, along with plant-derived and synthetic cannabinoids, interact with the type 1 (CB(1)) and 2 (CB(2)) cannabinoid receptors and the GPR55 receptor to regulate cellular function through a variety of signaling pathways. Endocannabinoids are produced in bone, but the mechanisms that regulate their production are unclear. Skeletal phenotyping of mice with targeted inactivation of cannabinoid receptors and pharmacological studies have shown that cannabinoids play a key role in the regulation of bone metabolism. Mice with CB(1) deficiency have high peak bone mass as a result of an osteoclast defect but develop age-related osteoporosis as a result of impaired bone formation and accumulation of bone marrow fat. Mice with CB(2) deficiency have relatively normal peak bone mass but develop age-related osteoporosis as a result of increased bone turnover with uncoupling of bone resorption from bone formation. Mice with GPR55 deficiency have increased bone mass as a result of a defect in the resorptive activity of osteoclasts, but bone formation is unaffected. Cannabinoids are also produced within synovial tissues, and preclinical studies have shown that cannabinoid receptor ligands are effective in the treatment of inflammatory arthritis. These data indicate that cannabinoid receptors and the enzymes responsible for ligand synthesis and breakdown play important roles in bone remodeling and in the pathogenesis of joint disease.

  5. Muscle-bone Interactions During Fracture Healing

    Science.gov (United States)

    2015-03-01

    physical trauma31, orthopaedic surgery32, or due to disease like fibrodysplasia ossificans progressiva, which has been identified to be a result of a...responsible for bone healing may provide opportunities to develop therapies to augment normal physiologic mechanisms underlying bone regeneration. Current... osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab 2008; 26:159-64. 70. Hill M, Goldspink G. Expression and splicing of the in- sulin

  6. Bone Health and Osteoporosis.

    Science.gov (United States)

    Lupsa, Beatrice C; Insogna, Karl

    2015-09-01

    Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue leading to decreased bone strength and an increased risk of low-energy fractures. Central dual-energy X-ray absorptiometry measurements are the gold standard for determining bone mineral density. Bone loss is an inevitable consequence of the decrease in estrogen levels during and following menopause, but additional risk factors for bone loss can also contribute to osteoporosis in older women. A well-balanced diet, exercise, and smoking cessation are key to maintaining bone health as women age. Pharmacologic agents should be recommended in patients at high risk for fracture.

  7. Exercise frequency and bone mineral density development in exercising postmenopausal osteopenic women. Is there a critical dose of exercise for affecting bone? Results of the Erlangen Fitness and Osteoporosis Prevention Study.

    Science.gov (United States)

    Kemmler, Wolfgang; von Stengel, Simon; Kohl, Matthias

    2016-08-01

    Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (pexercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation.

  8. 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

  9. Virtual temporal bone

    Institute of Scientific and Technical Information of China (English)

    QIU Ming-guo; ZHANG Shao-xiang; LIU Zheng-jin; TAN Li-wen; WANG Yu-su; DENG Jun-hui; TANG Ze-sheng

    2002-01-01

    Objective:To provide the virtual model of the temporal bone for improving 3-dimension (3D) visualization of the inner ear. Methods: Plastination technique was used to make equidistant serial thin sections 1.0 mm in thickness. On SGI workstation, a Contours+Marching Cubes algorithm was selected to reconstruct the temporal bone and intratemporal structures in 3D, then to view the middle ear, inner ear, and intratemporal structures which imitate the scenes observed by the traditional endoscopy. Results: The virtual model of the temporal bone was successfully constructed, with all reconstructed structures being represented individually or jointly and being rotated continuously in any plane. Virtual endoscopy improved 3D visualization of the middle ear, inner ear, and intratemporal structures. Conclusion: The reconstructed model can be used for the medical students to rehearse or review the surgeries on this part and for the surgeons to develop a new approach for operation. Virtual otoscopy stands as a promising new visualization technique for elucidating the structure and relation of the middle ear, inner ear, and intratemporal structures.

  10. Multiscale Modeling of Bone

    Science.gov (United States)

    2014-12-01

    DISEASE Both age and disease can affect the structure of bone, the effects of which are often similar. The most common bone disease is osteoporosis ... Osteoporosis is a disease that results in reduced bone mass and density. This reduction of bone mass and density has a greater impact on trabecular...Bone loss in females is linked to a decrease in estrogen ; the decrease of estrogen associated with menopause increases osteoclast activity [89]. This

  11. Bone age assessment for young children from newborn to 7-year-old using carpal bones

    Science.gov (United States)

    Zhang, Aifeng; Gertych, Arkadiusz; Liu, Brent J.; Huang, H. K.

    2007-03-01

    A computer-aided-diagnosis (CAD) method has been previously developed based on features extracted from phalangeal regions of interest (ROI) in a digital hand atlas, which can assess bone age of children from ages 7 to 18 accurately. Therefore, in order to assess the bone age of children in younger ages, the inclusion of carpal bones is necessary. In this paper, we developed and implemented a knowledge-based method for fully automatic carpal bone segmentation and morphological feature analysis. Fuzzy classification was then used to assess the bone age based on the selected features. Last year, we presented carpal bone segmentation algorithm. This year, research works on procedures after carpal bone segmentation including carpal bone identification, feature analysis and fuzzy system for bone age assessment is presented. This method has been successfully applied on all cases in which carpal bones have not overlapped. CAD results of total about 205 cases from the digital hand atlas were evaluated against subject chronological age as well as readings of two radiologists. It was found that the carpal ROI provides reliable information in determining the bone age for young children from newborn to 7-year-old.

  12. Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life:the Medical Research Council (MRC) National Survey of Health and Development

    OpenAIRE

    Cole, T J; Kuh, Diana J L; Johnson, W.; Ward, K A; Howe, L.D.; Adams, J E; Hardy, R; Ong, K. K.

    2016-01-01

    BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) ...

  13. Observation of Development Regularity of Leg Bone in Cyan- shank Partridge Chickens%青脚麻鸡腿骨发育规律的观察

    Institute of Scientific and Technical Information of China (English)

    宁康健; 吕锦芳; 姜锦鹏; 应如海; 冯保明

    2011-01-01

    400 Cyan - Shank Partridge Chickens were used for this experiment, Eight Chickens (female and male were half to half) were selected and weighed in 21,28,35,42,49,56 days at random. Then separated the femur and tibia, weighed and measured its length, analysed bone index, relative growth and cumulative growth in order to observe the development regularity of leg bone in Cyan - Shank Partridge Chicken at 3 to 8 Weeks. The results showed that the growing peak of absolute length in femur were later than the absolute weight gain both for the male and female(49 vs 42 days old), while the growing peak of absolute length were earlier than the ab- solute weight gain in tibia. Till the 56th day, the length of femur and tibia had no difference in male and femal, but the weight of femur and tibia in cock were both heavier than that in hen. Compared with the femur, the tibia grew faster in the early both for the male and female and the tibia index was higher than the femur index. The weight of femur and tibia in different gender have a highly positive correlation with the increasing days.%400只青脚麻鸡分别于21、28、35、42、49、56日龄随机抽取样鸡8只(公、母各半)称重,分离股骨和胫骨,称重并测量长度,分析骨指数、相对生长和累积生长,观察青脚麻鸡3~8周龄腿骨的发育规律。结果表明:公、母鸡股骨的绝对长度生长峰期出现落后于绝对增重,即49日龄对42日龄,而公、母鸡的胫骨绝对长度生长峰期出现先于绝对增重。截至56日龄,公、母鸡的股骨和胫骨长度没有差异,而公鸡的股骨和胫骨重均大于母鸡,与股骨比较,公、母鸡的胫骨均在早期生长较快,胫骨指数大于股骨指数。不同性别的股骨和胫骨重均与其日龄的增加呈高度正相关。

  14. The effects of dynamic compression on the development of cartilage grafts engineered using bone marrow and infrapatellar fat pad derived stem cells.

    Science.gov (United States)

    Luo, Lu; Thorpe, Stephen D; Buckley, Conor T; Kelly, Daniel J

    2015-09-21

    Bioreactors that subject cell seeded scaffolds or hydrogels to biophysical stimulation have been used to improve the functionality of tissue engineered cartilage and to explore how such constructs might respond to the application of joint specific mechanical loading. Whether a particular cell type responds appropriately to physiological levels of biophysical stimulation could be considered a key determinant of its suitability for cartilage tissue engineering applications. The objective of this study was to determine the effects of dynamic compression on chondrogenesis of stem cells isolated from different tissue sources. Porcine bone marrow (BM) and infrapatellar fat pad (FP) derived stem cells were encapsulated in agarose hydrogels and cultured in a chondrogenic medium in free swelling (FS) conditions for 21 d, after which samples were subjected to dynamic compression (DC) of 10% strain (1 Hz, 1 h d(-1)) for a further 21 d. Both BM derived stem cells (BMSCs) and FP derived stem cells (FPSCs) were capable of generating cartilaginous tissues with near native levels of sulfated glycosaminoglycan (sGAG) content, although the spatial development of the engineered grafts strongly depended on the stem cell source. The mechanical properties of cartilage grafts generated from both stem cell sources also approached that observed in skeletally immature animals. Depending on the stem cell source and the donor, the application of DC either enhanced or had no significant effect on the functional development of cartilaginous grafts engineered using either BMSCs or FPSCs. BMSC seeded constructs subjected to DC stained less intensely for collagen type I. Furthermore, histological and micro-computed tomography analysis showed mineral deposition within BMSC seeded constructs was suppressed by the application of DC. Therefore, while the application of DC in vitro may only lead to modest improvements in the mechanical functionality of cartilaginous grafts, it may play an important

  15. EXPERIMENTAL DEVELOPMENT OF BIO-BASED POLYMER MATRIX BUILDING MATERIAL AND FISH BONE DIAGRAM FOR MATERIAL EFFECT ON QUALITY

    Directory of Open Access Journals (Sweden)

    Asmamaw Tegegne

    2014-06-01

    Full Text Available These days cost of building materials are continuously increasing and the conventional construction materials for this particular purpose become low and low. The weight of conventional construction materials particularly building block is heavy and costly due to particularly cement. Thus, the objective of this paper is to develop an alternative light weight, high strength and relatively cost effective building material that satisfy the quality standard used in the country. A bio-based polymer matrix composite material for residential construction was experimentally developed. Sugar cane bagasse, thermoplastics (polyethylene g roup sand and red ash were used as materials alternatively. Mixing of the additives,melting of the hermoplastics, molding and curing (dryingwere the common methods used on the forming process of the samples. Mechanical behavior evaluation (testing of the product was carried out. Totally 45 specimens were produced and three replicate tests were performed per each test type. Quality analysis was carried out for group B material using Ishikawa diagram. The tensile strength of group A specimen was approximately 3 times greater than that of group B specimens. The compression strength of group A specimens were nearly 2 times greater than group B. Comparing to the conventional building materials(concert block and agrostoneproduced in the country, which the compression strength is 7Mpa and 16Mpa respectively, the newly produced materials show much better results in which Group A is 25.66 Mpa and group B is 16.66 Mpa. energy absorption capacity of group A specimens was approximately 3 times better than that of group B. Water absorption test was carried out for both groups and both showed excellent resistivity. Group A composite material specimens, showed better results in all parameters.

  16. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-03-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  17. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-01-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  18. 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.

  19. Reduced Bone Mineral Density and Bone Metabolism in Aquaporin-1 Knockout Mice

    Institute of Scientific and Technical Information of China (English)

    WU Qing-tian; MA Qing-jie; HE Cheng-yan; WANG Cai-xia; GAO Shi; HOU Xia; MA Tong-hui

    2007-01-01

    An overt phenotype of aquaporin-1 knockout(AQP1 ko) mice is growth retardation, suggesting possible defects in bone development and metabolism. In the present study, we analyzed the bone mineral density(BMD), bone calcium and phosphorus contents, and bone metabolism in an AQP1 ko mouse model. The BMD of femurs in AQP1 ko mice was significantly lower than that of litter-matched wildtype mice as measured by dual energy X-ray absorptiometry. Consistently, the contents of bone total calcium and phosphorus were also significantly lower in AQP1 ko mice. The reduced BMD caused by AQP1 deficiency mainly affect male mice. Bone metabolic activity, as indicated by 99mTc-MDP absorption measurements, was remarkably reduced in AQP1 ko mice. These results provide the first evidence that AQP1 play an important role in bone structure and metabolism.

  20. Regulation of Bone Metabolism.

    Science.gov (United States)

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi

    2017-04-01

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

  1. Regulation of Bone Metabolism

    Science.gov (United States)

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi

    2017-01-01

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

  2. Bioresorbable and nonresorbable polymers for bone tissue engineering.

    Science.gov (United States)

    Girones Molera, Jordi; Mendez, José Alberto; San Roman, Julio

    2012-01-01

    In recent years, bone tissue engineering has emerged as one of the main research areas in the field of regenerative biomedicine. Frequency and relevance age-related diseases, such as healing and regeneration of bone tissues, are rising due to increasing life expectancy. Even though bone tissue has excellent self-regeneration ability, when bone defects exceed a critical size, impaired bone formation can occur and surgical intervention becomes mandatory. Bone tissue engineering represents an alternative approach to conventional bone transplants. The main aim of tissue engineering is to repair, regenerate or reconstruct damaged or degenerative tissue. This review presents an overview on the main materials, techniques and strategies in the field of bone tissue engineering. Whilst presenting some reviews recently published that deepen on each of the sections of the paper, this review article aims to present some of the most relevant advances, both in terms of new materials and strategies, currently being developed for bone repair and regeneration.

  3. Microelements for bone boost: the last but not the least

    Science.gov (United States)

    Pepa, Giuseppe Della; Brandi, Maria Luisa

    2016-01-01

    Summary Osteoporosis is a major public health problem affects many millions of people around the world. It is a metabolic bone disease characterized by loss of bone mass and strength, resulting in increased risk of fractures. Several lifestyle factors are considered to be important determinants of it and nutrition can potentially have a positive impact on bone health, in the development and maintenance of bone mass and in the prevention of osteoporosis. There are potentially numerous nutrients and dietary components that can influence bone health, and these range from the macronutrients to micronutrients. In the last decade, epidemiological studies and clinical trials showed micronutrients can potentially have a positive impact on bone health, preventing bone loss and fractures, decreasing bone resorption and increasing bone formation. Consequently, optimizing micronutrients intake might represent an effective and low-cost preventive measure against osteoporosis. PMID:28228778

  4. 骨生化指标在骨肿瘤中的临床应用进展%Clinical application progress of bone biochemical markers in bone tumors

    Institute of Scientific and Technical Information of China (English)

    周定; 张琪琪; 胡勇

    2014-01-01

    relapse ( prognostic judgment ) and developing new drugs to block abnormal metabolic pathways of bone tumors to achieve the goal of treatment ( therapeutic effects ).

  5. Characterization of bone quality in prostate cancer bone metastases using Raman spectroscopy

    Science.gov (United States)

    Bi, Xiaohong; Patil, Chetan; Morrissey, Colm; Roudier, Martine P.; Mahadevan-Jansen, Anita; Nyman, Jeffry

    2010-02-01

    Prostate cancer is the most common primary tumor in men, with a high propensity to metastasize to bone. Bone metastases in prostate cancer are associated with active pathologic bone remodeling, leading to increased mortality and morbidity. Detailed characterization of bone metastases is important in the management of prostate cancer. Raman spectroscopy was applied in this study to investigate the structure and composition of metastatic bone in prostate cancer with the ultimate goal of identifying spectral features that are related to the alterations in bone quality as the bone metastases develop. Osteoblastic-, osteolytic- and tumor-absent bone specimens from prostate cancer patients were investigated using bench-top Raman microspectroscopy. Raman derived measurements of collagen mineralization, mineral crystallinity, and carbonate substitution were calculated. The osteolytic lesions demonstrated significantly lower collagen mineralization, determined by phosphate ν1/proline, and higher carbonate substitution than normal and osteoblastic bones. Mineral crystallinity was significantly lower in both blastic and lytic specimens. In addition, a significant increase in the ratio of hydroxyproine: proline was observed in the osteoblastic specimen, indicating an increase in the content of hydroxyproline at the blastic lesions. This study demonstrate that Raman spectroscopy shows promise in determining alterations in osteoblastic and osteolytic bone metastases as well as assessing the response of metastatic bone to therapies.

  6. 38 CFR 4.44 - The bones.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false The bones. 4.44 Section 4... DISABILITIES Disability Ratings The Musculoskeletal System § 4.44 The bones. The osseous abnormalities incident... convalescence, and progress of recovery with development of permanent residuals. With shortening of a long...

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

    Science.gov (United States)

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

    2009-04-01

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

  8. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    Science.gov (United States)

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities.

  9. [Bone and Men's Health. Bone selective androgen receptor modulators].

    Science.gov (United States)

    Furuya, Kazuyuki

    2010-02-01

    Androgen, one of the sex steroid hormones shows various biological activities on the corresponding various tissues. Many efforts to produce novel drug materials maintaining a desired biological activity with an adequate tissue selectivity, which is so-called selective androgen receptor modulators (SARMs) , are being performed. As one of such efforts, studies on SARMs against bone tissues which possess a significant potential to stimulate a bone formation with reducing undesirable androgenic virilizing activities are in progress all over the world. This review focuses on the research and development activities of such SARMs and discuses their usefulness for the treatment of osteoporosis.

  10. Aneurysmal bone cysts treated by curettage, cryotherapy and bone grafting

    NARCIS (Netherlands)

    Schreuder, HWB; Veth, RPH; Pruszczynski, M; Lemmens, JAM; Molenaar, WM; Schraffordt Koops, H.

    1997-01-01

    We treated 26 patients with 27 aneurysmal bone cysts by curettage and cryotherapy and evaluated local tumour control. complications and functional outcome. The mean follow-up time was 37 months (19 to 154), There was local recurrence in one patient. Two patients developed deep wound infections and o

  11. Development of a bone reconstruction technique using a solid free-form fabrication (SFF)-based drug releasing scaffold and adipose-derived stem cells.

    Science.gov (United States)

    Lee, Jin Woo; Kim, Ki-Joo; Kang, Kyung Shin; Chen, Shaochen; Rhie, Jong-Won; Cho, Dong-Woo

    2013-07-01

    For tissue regeneration, three essential components of scaffolds, signals (biomolecules), and cells are required. Moreover, because bony defects are three-dimensional in many clinical circumstances, an exact 3D scaffold is important. Therefore, we proposed an effective reconstruction tool for cranial defects using human adipose-derived stem cells (hADSCs) and a 3D functional scaffold fabricated by solid free-form fabrication (SFF) technology that secretes biomolecules. We fabricated poly(propylene fumarate)-based 3D scaffolds with embedded microsphere-deliverable bone morphogenetic protein-2 (BMP-2) by microstereolithography. BMP-2-loaded SFF scaffolds with/without hADSCs (SFF/BMP/hADSCs scaffolds and SFF/BMP scaffolds, respectively) and BMP-2-unloaded SFF scaffolds (SFF scaffolds) were then implanted in rat crania, and in vivo bone formation was observed. Analyses of bone formation areas using micro-computed tomography (micro-CT) showed the superiority of SFF/BMP/hADSCs scaffolds. Hematoxylin and eosin stain, Masson's trichrome stain, and collagen type-I stain supported the results of the micro-CT scan. And human leukocyte antigen-ABC showed that seeded, differentiated hADSCs were well grown and changed to the bone tissue at the inside of the scaffold. Results showed that our combination of a functional 3D scaffold and hADSCs may be a useful tool for improving the reconstruction quality of severe bony defects in which thick bone is required.

  12. Myeloma bone disease: Pathophysiology and management

    Science.gov (United States)

    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 abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases tumor growth, directly stimulates the OCL formation, and induces cells in the marrow microenvironment to produce factors that drive OCL formation and suppress OBL formation. Factors produced by marrow stromal cells and OCL promote tumor growth through direct action on myeloma cells and by increasing angiogenesis. Current therapies targeting MMBD focus on preventing osteoclastic bone destruction; however regulators of OBL inhibition in MMBD have also been identified, and targeted agents with a potential anabolic effect in MMBD are under investigation. This review will discuss the mechanisms responsible for MMBD and therapeutic approaches currently in use and in development for the management of MMBD. PMID:26909272

  13. Early diagenesis and recrystallization of bone

    Science.gov (United States)

    Keenan, Sarah W.; Engel, Annette Summers

    2017-01-01

    One of the most challenging problems in paleobiology is determining how bone transforms from a living tissue into a fossil. The geologic record is replete with vertebrate fossils preserved from a range of depositional environments, including wetland systems. However, thermodynamic models suggest that bone (modeled as hydroxylapatite) is generally unstable in a range of varying geochemical conditions and should readily dissolve if it does not alter to a more thermodynamically stable phase, such as a fluorine-enriched apatite. Here, we assess diagenesis of alligator bone from fleshed, articulated skeletons buried in wetland soils and from de-fleshed bones in experimental mesocosms with and without microbial colonization. When microbial colonization of bone was inhibited, bioapatite recrystallization to a more stable apatite phase occurred after one month of burial. Ca-Fe-phosphate phases in bone developed after several months to years due to ion substitutions from the protonation of the hydroxyl ion. These rapid changes demonstrate a continuum of structural and bonding transformations to bone that have not been observed previously. When bones were directly in contact with sediment and microbial cells, rapid bioerosion and compositional alteration occurred after one week, but slowed after one month because biofilms reduced exposed surfaces and subsequent bioapatite lattice substitutions. Microbial contributions are likely essential in forming stable apatite phases during early diagenesis and for enabling bone preservation and fossilization.

  14. A novel bio-inorganic bone implant containing deglued bone, chitosan and gelatin

    Indian Academy of Sciences (India)

    G Saraswathy; S Pal; C Rose; T P Sastry

    2001-08-01

    With the aim of developing an ideal bone graft, a new bone grafting material was developed using deglued bone, chitosan and gelatin. Deglued bone (DGB) which is a by-product of bone glue industries and has the close crystallographic similarities of hydroxyapatite was used as main component in the preparation of bone implant. Chitosan was prepared from the exoskeleton of prawn (Pinaeus indicus, family Crustaceae) which is a by-product of seafood industries. Chitosan gives toughness to the product and do not allow the DGB particles to wither away when the implant is placed in the defect. Gelatin was used as binder for the preparation of DGB–chitosan composite. The DGB, chitosan and DGB–chitosan–gelatin composite, which were prepared in the laboratory, were analysed for their physicochemical properties by infrared spectroscopy, X-ray diffraction and scanning electron microscopy studies.

  15. Hyoid bone fusion and bone density across the lifespan: prediction of age and sex.

    Science.gov (United States)

    Fisher, Ellie; Austin, Diane; Werner, Helen M; Chuang, Ying Ji; Bersu, Edward; Vorperian, Houri K

    2016-06-01

    The hyoid bone supports the important functions of swallowing and speech. At birth, the hyoid bone consists of a central body and pairs of right and left lesser and greater cornua. Fusion of the greater cornua with the body normally occurs in adulthood, but may not occur at all in some individuals. The aim of this study was to quantify hyoid bone fusion across the lifespan, as well as assess developmental changes in hyoid bone density. Using a computed tomography imaging studies database, 136 hyoid bones (66 male, 70 female, ages 1-to-94) were examined. Fusion was ranked on each side and hyoid bones were classified into one of four fusion categories based on their bilateral ranks: bilateral distant non-fusion, bilateral non-fusion, partial or unilateral fusion, and bilateral fusion. Three-dimensional hyoid bone models were created and used to calculate bone density in Hounsfield units. Results showed a wide range of variability in the timing and degree of hyoid bone fusion, with a trend for bilateral non-fusion to decrease after age 20. Hyoid bone density was significantly lower in adult female scans than adult male scans and decreased with age in adulthood. In sex and age estimation models, bone density was a significant predictor of sex. Both fusion category and bone density were significant predictors of age group for adult females. This study provides a developmental baseline for understanding hyoid bone fusion and bone density in typically developing individuals. Findings have implications for the disciplines of forensics, anatomy, speech pathology, and anthropology.

  16. Osteochondroma (Bone Tumor)

    Science.gov (United States)

    ... to be the most common benign bone tumor, accounting for 35% to 40% of all benign bone ... imaging scans. Doctors may also request computed tomography (CT) scans or magnetic resonance imaging (MRI) scans to ...

  17. Bone mineral density test

    Science.gov (United States)

    BMD test; Bone density test; Bone densitometry; DEXA scan; DXA; Dual-energy x-ray absorptiometry; p-DEXA; Osteoporosis-BMD ... need to undress. This scan is the best test to predict your risk of fractures. Peripheral DEXA ( ...

  18. Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

    Energy Technology Data Exchange (ETDEWEB)

    Akita, Shingo; Kubota, Koji [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Kobayashi, Akira, E-mail: kbys@shinshu-u.ac.jp [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Misawa, Ryosuke; Shimizu, Akira; Nakata, Takenari; Yokoyama, Takahide [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Takahashi, Masafumi [Center for Molecular Medicine Division of Bioimaging Sciences, Jichi Medical University, 3311-1 Yakushiji, Shimono, Tochigi 329-0498 (Japan); Miyagawa, Shinichi [Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer BMC-derived PSCs play a role in a rat CDE diet-induced pancreatitis model. Black-Right-Pointing-Pointer BMC-derived PSCs contribute mainly to the early stage of pancreatic fibrosis. Black-Right-Pointing-Pointer BMC-derived activated PSCs can produce PDGF and TGF {beta}1. -- Abstract: Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in various organs, including the pancreas. However, the contribution of these cells to pancreatic fibrosis has not been fully discussed. The present study examined the possible involvement of pancreatic stellate cells (PSCs) originating from BMCs in the development of pancreatic fibrosis in a clinically relevant rat model of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE) diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent protein (GFP) were transplanted into lethally irradiated male rats. Once chimerism was established, acute pancreatitis was induced by a CDE diet. Chronological changes in the number of PSCs originating from the donor BMCs were examined using double immunofluorescence for GFP and markers for PSCs, such as desmin and alpha smooth muscle actin ({alpha}SMA), 1, 3 and 8 weeks after the initiation of CDE feeding. We also used immunohistochemical staining to evaluate whether the PSCs from the BMCs produce growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF) {beta}1. The percentage of BMC-derived activated PSCs increased significantly, peaking after 1 week of CDE treatment (accounting for 23.3 {+-} 0.9% of the total population of activated PSCs) and then decreasing. These cells produced both PDGF and TGF{beta}1 during the early stage of pancreatic fibrosis. Our results suggest that PSCs originating from BMCs contribute mainly to the early stage of pancreatic injury, at least in part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

  19. Development of an efficient, non-viral transfection method for studying gene function and bone growth in human primary cranial suture mesenchymal cells reveals that the cells respond to BMP2 and BMP3

    Directory of Open Access Journals (Sweden)

    Dwivedi Prem P

    2012-08-01

    Full Text Available Abstract Background Achieving efficient introduction of plasmid DNA into primary cultures of mammalian cells is a common problem in biomedical research. Human primary cranial suture cells are derived from the connective mesenchymal tissue between the bone forming regions at the edges of the calvarial plates of the skull. Typically they are referred to as suture mesenchymal cells and are a heterogeneous population responsible for driving the rapid skull growth that occurs in utero and postnatally. To better understand the molecular mechanisms involved in skull growth, and in abnormal growth conditions, such as craniosynostosis, caused by premature bony fusion, it is essential to be able to easily introduce genes into primary bone forming cells to study their function. Results A comparison of several lipid-based techniques with two electroporation-based techniques demonstrated that the electroporation method known as nucleofection produced the best transfection efficiency. The parameters of nucleofection, including cell number, amount of DNA and nucleofection program, were optimized for transfection efficiency and cell survival. Two different genes and two promoter reporter vectors were used to validate the nucleofection method and the responses of human primary suture mesenchymal cells by fluorescence microscopy, RT-PCR and the dual luciferase assay. Quantification of bone morphogenetic protein (BMP signalling using luciferase reporters demonstrated robust responses of the cells to both osteogenic BMP2 and to the anti-osteogenic BMP3. Conclusions A nucleofection protocol has been developed that provides a simple and efficient, non-viral alternative method for in vitro studies of gene and protein function in human skull growth. Human primary suture mesenchymal cells exhibit robust responses to BMP2 and BMP3, and thus nucleofection can be a valuable method for studying the potential competing action of these two bone growth factors in a model

  20. Selenoprotein P is the essential selenium transporter for bones.

    Science.gov (United States)

    Pietschmann, Nicole; Rijntjes, Eddy; Hoeg, Antonia; Stoedter, Mette; Schweizer, Ulrich; Seemann, Petra; Schomburg, Lutz

    2014-05-01

    Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations.

  1. Collagen osteoid-like model allows kinetic gene expression studies of non-collagenous proteins in relation with mineral development to understand bone biomineralization.

    Science.gov (United States)

    Silvent, Jérémie; Nassif, Nadine; Helary, Christophe; Azaïs, Thierry; Sire, Jean-Yves; Guille, Marie Madeleine Giraud

    2013-01-01

    Among persisting questions on bone calcification, a major one is the link between protein expression and mineral deposition. A cell culture system is here proposed opening new integrative studies on biomineralization, improving our knowledge on the role played by non-collagenous proteins in bone. This experimental in vitro model consisted in human primary osteoblasts cultured for 60 days at the surface of a 3D collagen scaffold mimicking an osteoid matrix. Various techniques were used to analyze the results at the cellular and molecular level (adhesion and viability tests, histology and electron microscopy, RT- and qPCR) and to characterize the mineral phase (histological staining, EDX, ATG, SAED and RMN). On long term cultures human bone cells seeded on the osteoid-like matrix displayed a clear osteoblast phenotype as revealed by the osteoblast-like morphology, expression of specific protein such as alkaline phosphatase and expression of eight genes classically considered as osteoblast markers, including BGLAP, COL1A1, and BMP2. Von Kossa and alizarine red allowed us to identify divalent calcium ions at the surface of the matrix, EDX revealed the correct Ca/P ratio, and SAED showed the apatite crystal diffraction pattern. In addition RMN led to the conclusion that contaminant phases were absent and that the hydration state of the mineral was similar to fresh bone. A temporal correlation was established between quantified gene expression of DMP1 and IBSP, and the presence of hydroxyapatite, confirming the contribution of these proteins to the mineralization process. In parallel a difference was observed in the expression pattern of SPP1 and BGLAP, which questioned their attributed role in the literature. The present model opens new experimental possibilities to study spatio-temporal relations between bone cells, dense collagen scaffolds, NCPs and hydroxyapatite mineral deposition. It also emphasizes the importance of high collagen density environment in bone cell

  2. 腌菜型复合骨汤肉酱调料的开发%Development of Complex Seasoning of Meat Sauce with Bone Soup and Pickles

    Institute of Scientific and Technical Information of China (English)

    郭秀兰; 王文亭; 肖龙泉; 李杉杉; 王卫; 刘达玉

    2014-01-01

    The livestock bone is used as main material,and chicken bone,crucian,etc.are added with a small quantity to reduce fishy smell.Bone oil is separated by centrifuge after all the materials are boiled,and the clear soup remainder is made into a complex bone puree by vacuum concentration.Stir livestock and poultry meat pieces into minced meat with deodorization or without deodorization,then being fried with pickles to be as meat solids.Finally,pack bone oil,bone puree and solids into bags according to a certain ratio,and complex meat sauce products are obtained after atmospheric steriliza-tion,the shelf life can be more than 6 months,the product may be used as convenient seasoning of rice flour noodles,vermicelli,noodles,soup and cooked food.%以畜骨为主要原料,并辅以鸡骨、鲫鱼等来减轻腥味,组合熬制后经过离心分离得到复合骨油,!汤真空浓缩制备复合骨浓汤。再用畜禽分割碎肉,经过脱膻或不脱膻后搅成肉糜,与腌菜一并经过炒制后作为肉酱固形物,最后将骨油、骨浓汤、固形物按一定比例装袋,常压杀菌后得到复合肉酱成品,保质期达6个月以上,可作为米线、粉丝、面条、汤汁、菜肴的方便调料。

  3. Androgens and bone.

    Science.gov (United States)

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

    2004-06-01

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

  4. Gracile bone dysplasias

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, Kazimierz [Department of Medical Imaging, The Children' s Hospital at Westmead, Locked Bag 4001, Westmead 2145, NSW (Australia); Masel, John [Department of Radiology, Royal Children' s Hospital, Brisbane (Australia); Sillence, David O. [Department of Paediatrics and Child Health, The University of Sydney (Australia); Arbuckle, Susan [Department of Anatomical Pathology, The Children' s Hospital at Westmead, NSW (Australia); Juttnerova, Vera [Oddeleni Lekarske Genetiky, Hradec Kralove (Czech Republic)

    2002-09-01

    Gracile bone dysplasias constitute a group of disorders characterised by extremely slender bones with or without fractures. We report four newborns, two of whom showed multiple fractures. Two babies had osteocraniostenosis and one had features of oligohydramnios sequence. The diagnosis in the fourth newborn, which showed thin long bones and clavicles and extremely thin, poorly ossified ribs, is uncertain. Exact diagnosis of a gracile bone dysplasia is important for genetic counselling and medico-legal reasons. (orig.)

  5. 2009 Santa Fe Bone symposium.

    Science.gov (United States)

    Lewiecki, E Michael; Bilezikian, John P; Laster, Andrew J; Miller, Paul D; Recker, Robert R; Russell, R Graham G; Whyte, Michael P

    2010-01-01

    Osteoporosis is a common skeletal disease with serious clinical consequences because of fractures. Despite the availability of clinical tools to diagnose osteoporosis and assess fracture risk, and drugs proven to reduce fracture risk, it remains a disease that is underdiagnosed and undertreated. When treatment is started, it is commonly not taken correctly or long enough to be effective. Recent advances in understanding of the regulators and mediators of bone remodeling have led to new therapeutic targets and the development of drugs that may offer advantages over current agents in reducing the burden of osteoporotic fractures. Many genetic factors that play a role in the pathogenesis of osteoporosis and metabolic bone disease have now been identified. At the 2009 Santa Fe Bone Symposium, held in Santa Fe, New Mexico, USA, the links between advances in genetics, basic bone science, recent clinical trials, and new and emerging therapeutic agents were presented and explored. Socioeconomic challenges and opportunities in the care of osteoporosis were discussed. This is a collection of medical essays based on key presentations at the 2009 Santa Fe Bone Symposium.

  6. A-raf and B-raf are dispensable for normal endochondral bone development, and parathyroid hormone-related peptide suppresses extracellular signal-regulated kinase activation in hypertrophic chondrocytes.

    Science.gov (United States)

    Provot, Sylvain; Nachtrab, Gregory; Paruch, Jennifer; Chen, Adele Pin; Silva, Alcino; Kronenberg, Henry M

    2008-01-01

    Parathyroid hormone-related peptide (PTHrP) and the parathyroid hormone-PTHrP receptor increase chondrocyte proliferation and delay chondrocyte maturation in endochondral bone development at least partly through cyclic AMP (cAMP)-dependent signaling pathways. Because data suggest that the ability of cAMP to stimulate cell proliferation involves the mitogen-activated protein kinase kinase kinase B-Raf, we hypothesized that B-Raf might mediate the proliferative action of PTHrP in chondrocytes. Though B-Raf is expressed in proliferative chondrocytes, its conditional removal from cartilage did not affect chondrocyte proliferation and maturation or PTHrP-induced chondrocyte proliferation and PTHrP-delayed maturation. Similar results were obtained by conditionally removing B-Raf from osteoblasts. Because A-raf and B-raf are expressed similarly in cartilage, we speculated that they may fulfill redundant functions in this tissue. Surprisingly, mice with chondrocytes deficient in both A-Raf and B-Raf exhibited normal endochondral bone development. Activated extracellular signal-regulated kinase (ERK) was detected primarily in hypertrophic chondrocytes, where C-raf is expressed, and the suppression of ERK activation in these cells by PTHrP or a MEK inhibitor coincided with a delay in chondrocyte maturation. Taken together, these results demonstrate that B-Raf and A-Raf are dispensable for endochondral bone development and they indicate that the main role of ERK in cartilage is to stimulate not cell proliferation, but rather chondrocyte maturation.

  7. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    OpenAIRE

    2007-01-01

    The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide) composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was...

  8. Enzymatic maceration of bone

    DEFF Research Database (Denmark)

    Uhre, Marie-Louise; Eriksen, Anne Marie; Simonsen, Kim Pilkjær;

    2015-01-01

    the bones. The DNA analysis showed that DNA was preserved on all the pieces of bones which were examined. Finally, the investigation suggests that enzyme maceration could be gentler on the bones, as the edges appeared less frayed. The enzyme maceration was also a quicker method; it took three hours compared...

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

    Science.gov (United States)

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

    2015-12-01

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

  10. Oxytocin and bone

    Science.gov (United States)

    Sun, Li; Zaidi, Mone; Zallone, Alberta

    2014-01-01

    One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR−/− mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

  11. Bone regeneration with cultured human bone grafts

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, T.; Nakajima, H. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology; Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Ohgushi, H.; Ueda, Y.; Takakura, Y. [Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Uemura, T.; Tateishi, T. [National Inst. for Advanced Interdisciplinary Research (NAIR), Ibaraki (Japan). Tsukuba Research Center; Enomoto, Y.; Ichijima, K. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology

    2001-07-01

    From 73 year old female patient, 3 ml of bone marrow was collected from the ilium. The marrow was cultured to concentrate and expand the marrow mesenchymal cells on a culture dish. The cultured cells were then subculturedeither on another culture dish or in porous areas of hydroxyapatite ceramics in the presence of dexamethasone and beta-glycerophosphate (osteo genic medium). The subculturedtissues on the dishes were analyzed by scanning electron microscopy (SEM), and subculturedtissues in the ceramics were implanted intraperitoneally into athymic nude mice. Vigorous growth of spindle-shaped cells and a marked formation of bone matrix beneath the cell layers was observed on the subculture dishes by SEM. The intraperitoneally implanted ceramics with cultured tissues revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the ceramics after 8 weeks. The in vitro bone formations on the culture dishes and in vivo bone formation in porous ceramics were detected. These results indicate that we can assemble an in vitro bone/ceramic construct, and due to the porous framework of the ceramic, the construct has osteogenic potential similar to that of autologous cancellous bone. A significant benefit of this method is that the construct can be made with only a small amount of aspirated marrow cells from aged patients with little host morbidity. (orig.)

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

    Science.gov (United States)

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

    2012-07-26

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

  13. Healing pattern of reamed bone following bone harvesting by a RIA device

    Directory of Open Access Journals (Sweden)

    DM Devine

    2015-01-01

    Full Text Available Intramedullary nailing has been used for decades to treat fractures of the long bones. However, complications related to the increase in medullary pressure culminated in the development of the Reamer Irrigator Aspirator (RIA. Since its first clinical use, the RIA has moved from a reaming device to a cell and autologous bone-harvesting tool. This increase in use brings with it further clinical questions; namely, does the endosteal bone regenerate sufficiently to allow subsequent reaming procedures. In the current study, endosteal bone regeneration post reaming was assessed in an ovine model. The study included six animals that had one tibia reamed, while the contralateral tibia acted as an intact control. Animals were administered fluorochrome labels in vivo, and bone regeneration was assessed using radiographical analysis. The endpoint of the study was 12 weeks post-surgery, at which time ex vivo analysis consisted of computed tomography and histological assessments. In vivo radiographs indicated limited healing of the reamed bone. However, ex vivo computer tomographical analysis indicated no significant differences in terms of bone volume between the reamed bone and the intact bone. Histological assessment of these regions indicated new bone formation. Fluorescent labelling indicates strong bone formation from 9 weeks post-surgery and as such, the bone formed at 12 weeks was immature in nature and was actively undergoing remodelling. These results indicate that bone regeneration post-reaming was continuing at three months. Therefore, given more time it may have sufficiently healed to allow a surgeon to use the intramedullary canal for a re-reaming procedure.

  14. Painful scoliosis due to superposed giant cell bone tumor and aneurysmal bone cyst in a child.

    Science.gov (United States)

    Togral, Guray; Arikan, Murat; Hasturk, Askin E; Gungor, Safak

    2014-07-01

    Giant cell bone tumors are the most common precursor lesions of aneurysmal bone cysts (ABCs) developing secondarily. In giant cell bone tumors containing an explicit ABC component, the observation of the solid component of the giant cell bone tumor plays a critical role in the separation of the primary ABC. In general, ABC cases together with giant cell tumors in the bone are diagnosed histopathologically. The combination of giant cell bone tumor with superposed ABC and that of painful scoliosis with backache is rarely seen in children. In this case study, we discussed the diagnosis and the treatment of a giant cell tumor and superposed an ABC present in the fifth lumbar spine in a pediatric patient admitted to our clinic with a complaint of acute scoliotic back pain.

  15. Mesenchymal Stem Cells and Nano-Bioceramics for Bone Regeneration.

    Science.gov (United States)

    Kankilic, Berna; Köse, Sevil; Korkusuz, Petek; Timuçin, Muharrem; Korkusuz, Feza

    Orthopedic disorders and trauma usually result in bone loss. Bone grafts are widely used to replace this tissue. Bone grafts excluding autografts unfortunately have disadvantages like evoking immune response, contamination and rejection. Autografts are of limited sources and optimum biomaterials that can replace bone have been searched for several decades. Bioceramics, which have the similar inorganic structure of natural bone, are widely used to regenerate bone or coat metallic implants. As people continuously look for a higher life quality, there are developments in technology almost everyday to meet their expectations. Nanotechnology is one of such technologies and it attracts everyone's attention in biomaterial science. Nano scale biomaterials have many advantages like larger surface area and higher biocompatibility and these properties make them more preferable than micro scale. Also, stem cells are used for bone regeneration besides nano-bioceramics due to their differentiation characteristics. This review covers current research on nano-bioceramics and mesenchymal stem cells and their role in bone regeneration.

  16. Bone scintiscanning updated.

    Science.gov (United States)

    Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I

    1976-03-01

    Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

  17. BONES WITH BIOCERAMICS

    Directory of Open Access Journals (Sweden)

    Wijianto Wijianto

    2017-01-01

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

  18. Chondromodulin I Is a Bone Remodeling Factor

    OpenAIRE

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

    2003-01-01

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

  19. Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

    OpenAIRE

    Starup-Linde, Jakob

    2013-01-01

    Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone marker...

  20. Guided Bone Regeneration with Novel Bioabsorbable Membranes

    Science.gov (United States)

    Koyama, Yoshihisa; Kikuchi, Masanori; Yamada, Takeki; Kanaya, Tomohiro; Matsumoto, Hiroko N.; Takakuda, Kazuo; Miyairi, Hiroo; Tanaka, Junzo

    Guided Bone Regeneration (GBR) is a method for bone tissue regeneration. In this method, membranes are used to cover bone defects and to block the invasion of the surrounding soft tissues. It would provide sufficient time for the osteogenic cells from bone marrow to proliferate and form new bony tissues. In spite of the potential usefulness of this method, no appropriate materials for the GBR membrane have been developed. Here we design the ideal mechanical properties of the GBR membranes and created novel materials, which is the composite of β-tricalcium phosphate and block copolymer of L-lactide, glycolide and ɛ-caplolactone. In the animal experiments with the use of the trial products, we observed significant enhancement in the bone regeneration and proved the effectiveness of the materials.

  1. The Digital Astronaut Project Bone Remodeling Model

    Science.gov (United States)

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

    2014-01-01

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

  2. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Tae-Ho Kim

    2016-01-01

    Full Text Available Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr cocoons spun by Rhus javanica (Bell. Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr or 100% ethanolic extract (eeGr on ovariectomy- (OVX- induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks augmented the inhibition of femoral bone mineral density (BMD, bone mineral content (BMC, and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

  3. Long bone histology of the subterranean rodent Bathyergus suillus (Bathyergidae): ontogenetic pattern of cortical bone thickening.

    Science.gov (United States)

    Montoya-Sanhueza, Germán; Chinsamy, Anusuya

    2017-02-01

    Patterns of bone development in mammals are best known from terrestrial and cursorial groups, but there is a considerable gap in our understanding of how specializations for life underground affect bone growth and development. Likewise, studies of bone microstructure in wild populations are still scarce, and they often include few individuals and tend to be focused on adults. For these reasons, the processes generating bone microstructural variation at intra- and interspecific levels are not fully understood. This study comprehensively examines the bone microstructure of an extant population of Cape dune molerats, Bathyergus suillus (Bathyergidae), the largest subterranean mammal endemic to the Western Cape of South Africa. The aim of this study is to investigate the postnatal bone growth of B. suillus using undecalcified histological sections (n = 197) of the femur, humerus, tibia-fibula, ulna and radius, including males and females belonging to different ontogenetic and reproductive stages (n = 42). Qualitative histological features demonstrate a wide histodiversity with thickening of the cortex mainly resulting from endosteal and periosteal bone depositions, whilst there is scarce endosteal resorption and remodeling throughout ontogeny. This imbalanced bone modeling allows the tissues deposited during ontogeny to remain relatively intact, thus preserving an excellent record of growth. The distribution of the different bone tissues observed in the cortex depends on ontogenetic status, anatomical features (e.g. muscle attachment structures) and location on the bone (e.g. anterior or lateral). The type of bone microstructure and modeling is discussed in relation to digging behavior, reproduction and physiology of this species. This study is the first histological assessment describing the process of cortical thickening in long bones of a fossorial mammal.

  4. Effects of obesity on bone metabolism

    Directory of Open Access Journals (Sweden)

    Cao Jay J

    2011-06-01

    Full Text Available Abstract Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely

  5. Stem cells in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2010-12-15

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  6. Automated bone age assessment of older children using the radius

    Science.gov (United States)

    Tsao, Sinchai; Gertych, Arkadiusz; Zhang, Aifeng; Liu, Brent J.; Huang, Han K.

    2008-03-01

    The Digital Hand Atlas in Assessment of Skeletal Development is a large-scale Computer Aided Diagnosis (CAD) project for automating the process of grading Skeletal Development of children from 0-18 years of age. It includes a complete collection of 1,400 normal hand X-rays of children between the ages of 0-18 years of age. Bone Age Assessment is used as an index of skeletal development for detection of growth pathologies that can be related to endocrine, malnutrition and other disease types. Previous work at the Image Processing and Informatics Lab (IPILab) allowed the bone age CAD algorithm to accurately assess bone age of children from 1 to 16 (male) or 14 (female) years of age using the Phalanges as well as the Carpal Bones. At the older ages (16(male) or 14(female) -19 years of age) the Phalanges as well as the Carpal Bones are fully developed and do not provide well-defined features for accurate bone age assessment. Therefore integration of the Radius Bone as a region of interest (ROI) is greatly needed and will significantly improve the ability to accurately assess the bone age of older children. Preliminary studies show that an integrated Bone Age CAD that utilizes the Phalanges, Carpal Bones and Radius forms a robust method for automatic bone age assessment throughout the entire age range (1-19 years of age).

  7. Mathematical model for bone mineralization

    Directory of Open Access Journals (Sweden)

    Svetlana V Komarova

    2015-08-01

    Full Text Available Defective bone mineralization has serious clinical manifestations, including deformities and fractures, but the regulation of this extracellular process is not fully understood. We have developed a mathematical model consisting of ordinary differential equations that describe collagen maturation, production and degradation of inhibitors, and mineral nucleation and growth. We examined the roles of individual processes in generating normal and abnormal mineralization patterns characterized using two outcome measures: mineralization lag time and degree of mineralization. Model parameters describing the formation of hydroxyapatite mineral on the nucleating centers most potently affected the degree of mineralization, while the parameters describing inhibitor homeostasis most effectively changed the mineralization lag time. Of interest, a parameter describing the rate of matrix maturation emerged as being capable of counter-intuitively increasing both the mineralization lag time and the degree of mineralization. We validated the accuracy of model predictions using known diseases of bone mineralization such as osteogenesis imperfecta and X-linked hypophosphatemia. The model successfully describes the highly non-linear mineralization dynamics, which includes an initial lag phase when osteoid is present but no mineralization is evident, then fast primary mineralization, followed by secondary mineralization characterized by a continuous slow increase in bone mineral content. The developed model can potentially predict the function for a mutated protein based on the histology of pathologic bone samples from mineralization disorders of unknown etiology.

  8. Automatic bone age assessment for young children from newborn to 7-year-old using carpal bones.

    Science.gov (United States)

    Zhang, Aifeng; Gertych, Arkadiusz; Liu, Brent J

    2007-01-01

    A computer-aided-diagnosis (CAD) method has been previously developed based on features extracted from phalangeal regions of interest (ROI) in a digital hand atlas, which can assess bone age of children from ages 7 to 18 accurately. Therefore, in order to assess the bone age of children in younger ages, the inclusion of carpal bones is necessary. However, due to various factors including the uncertain number of bones appearing, non-uniformity of soft tissue, low contrast between the bony structure and soft tissue, automatic segmentation and identification of carpal bone boundaries is an extremely challenging task. Past research works on carpal bone segmentation were performed utilizing dynamic thresholding. However, due to the limitation of the segmentation algorithm, carpal bones have not been taken into consideration in the bone age assessment procedure. In this paper, we developed and implemented a knowledge-based method for fully automatic carpal bone segmentation and morphological feature analysis. Fuzzy classification was then used to assess the bone age based on the selected features. This method has been successfully applied on all cases in which carpal bones have not overlapped. CAD results of total about 205 cases from the digital hand atlas were evaluated against subject chronological age as well as readings of two radiologists. It was found that the carpal ROI provides reliable information in determining the bone age for young children from newborn to 7-year-old.

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

    Science.gov (United States)

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

  10. Instructive function of surface structure of calcium phosphate ceramics in bone regeneration

    NARCIS (Netherlands)

    Zhang, Jingwei

    2016-01-01

    The incidence of patients which require spinal fusion or bone regeneration in large bone defects caused by trauma, tumors, tumor resection, infections or abnormal skeletal development, is on the rise. Traditionally, in both spinal fusion surgery and other bone regeneration approaches, bone grafts ar

  11. Ten-year prediction of osteoporosis from baseline bone mineral density: development of prognostic thresholds in healthy postmenopausal women. The Danish Osteoporosis Prevention Study

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Rejnmark, Lars; Nielsen, Stig Pors;

    2006-01-01

    Osteopenia is common in healthy women examined in the first year or two following menopause. Short-term fracture risk is low, but we lack algorithms to assess long-term risk of osteoporosis. Because bone loss proceeds at only a few percent per year, we speculated that baseline bone mineral density...... (BMD) would predict a large proportion of 10-year BMD and be useful for deriving predictive thresholds. We aimed to identify prognostic thresholds associated with less than 10% risk of osteoporosis by 10 years in the individual participant, in order to allow rational osteodensitometry and intervention....... We analyzed dual energy X-ray absorptometry (DXA) of the lumbar spine (LS) and femoral neck (FN) from 872 women, who participated in the non-HRT arms of the Danish Osteoporosis Prevention Study and had remained on no HRT, bisphosphonates or raloxifene since inclusion 10 years ago. We defined...

  12. Heterotopic bone formation following total shoulder arthroplasty

    DEFF Research Database (Denmark)

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

    1989-01-01

    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...... the glenohumeral and/or the glenoacromial space. There was no correlation between shoulder pain and the development of ossification. Shoulders with grade III heterotopic bone formation had a limited range of active elevation compared with shoulders without or with only a milder lesion. Men and patients...... 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....

  13. Metastasis and bone loss: advancing treatment and prevention.

    Science.gov (United States)

    Coleman, Robert E; Lipton, Allan; Roodman, G David; Guise, Theresa A; Boyce, Brendon F; Brufsky, Adam M; Clézardin, Philippe; Croucher, Peter I; Gralow, Julie R; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R; Smith, Matthew R; Suva, Larry J

    2010-12-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.

  14. Metastasis and bone loss: Advancing treatment and prevention

    Science.gov (United States)

    Coleman, Robert E.; Lipton, Allan; Roodman, G. David; Guise, Theresa A.; Boyce, Brendon F.; Brufsky, Adam M.; Clézardin, Philippe; Croucher, Peter I.; Gralow, Julie R.; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R.; Smith, Matthew R.; Suva, Larry J.

    2011-01-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy. PMID:20478658

  15. Novel Therapeutic Strategy for the Prevention of Bone Fractures

    Science.gov (United States)

    2015-02-01

    myostatin’s role in age- related bone loss, so that targeted therapies to prevent bone fractures by enhancing muscle and bone strength can be developed. We...loss of muscle mass in the form of sarcopenia, and loss of bone density and strength in the form of osteoporosis . Mus cle weakness and frailty contribute...Bollag, W.B., Curl, W.W., Yu, J., Isales, C.M., 2006. Age- related loss of muscle mass and bone strength in mice is associated with a decline in physical

  16. Bone building with bortezomib

    Science.gov (United States)

    Roodman, G. David

    2008-01-01

    In this issue of the JCI, Mukherjee et al. report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells (MSCs) — rather than mature osteoprogenitor cells — into osteoblasts, resulting in new bone formation (see the related article beginning on page 491). These results were observed when MSCs were implanted subcutaneously in mice or were used to treat a mouse model of postmenopausal bone loss. Others have reported that immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These results reflect the utility of targeting endogenous MSCs for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease. PMID:18219395

  17. EVALUATION OF TECHNIQUES FOR CLEANING EMBALMED CADAVER BONES

    Directory of Open Access Journals (Sweden)

    Bhawani Shankar Modi

    2014-12-01

    Full Text Available Objective: The present study was conducted to find new technique for development of bone specimens from cadavers. Material and methods: Long bones, skull and other bones from embalmed cadaver were taken and cleansed by various methods. Four methods were employed for preparing specimens. In 1st method bones were boiled in tap water for 7-8 hours on gas stove. In 2nd method bones were immersed in water with addition of detergent at constant temperature. In 3rd method bones were kept at constant temperature in water without addition of detergent. In 4th method bones were buried for one month under superficial surface of soil during rainy season after boiling the bones for 7-8 hours Observations: Use of detergent in warm water (65o C was good for cleaning long bones while best result for long bones as well as skull was seen with boiling followed by burial of embalmed specimens. Results were found as expected. Time consumed in the present study was less than old classical methods. Bones specimens formed were of high quality. Conclusions: Preparation of bone specimen by embalmed cadaver can be of immense value and time saver for many research institutes to get their self-prepared specimens. There are many more ways which has to be modified or rediscovered in this area of research, which has been neglected so far.

  18. Chondroblastoma of the patella with aneurysmal bone cyst.

    Science.gov (United States)

    Tan, Honglue; Yan, Mengning; Yue, Bing; Zeng, Yiming; Wang, You

    2014-01-01

    Chondroblastoma of the patella is rare. Aneurysmal bone cysts, which develop from a prior lesion such as a chondroblastoma, are seldom seen in the patella. The authors report a case of a 36-year-old man who presented with 2 years of right knee pain without calor, erythema, pain on palpation, or abnormal range of motion. Radiological studies suggested aneurysmal bone cyst. The lesion was excised with curettage and the residual cavity filled with autogenous bone graft. Histopathology revealed chondroblastoma associated with a secondary aneurysmal bone cyst. In the follow-up period, the patient demonstrated normal joint activities with no pain. Normal configuration of the patella and bone union were shown on plain radiographs. The authors present a review of the literature of all cases of patellar chondroblastoma with aneurysmal bone cyst. This case is the 14th report of aneurysmal bone cyst arising in a chondroblastoma of the patella. According to the literature, computed tomography and magnetic resonance imaging are useful in the study of these lesions. The pathologic diagnosis is based on the presence of chondroblastoma and aneurysmal bone cyst. Treatment of this lesion includes patellectomy, curettage alone, and curettage with bone grafting. Despite the risk of recurrence of this lesion in the patella, the authors first recommend curettage followed by filling the cavity with bone graft. To protect the anterior tension of the patella intraoperatively, the bone window should be made at the medial edge of the patella to perform the curettage and bone grafting.

  19. Recent advances in bone regeneration using adult stem cells.

    Science.gov (United States)

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

  20. Understanding Bone Strength Is Not Enough.

    Science.gov (United States)

    Hernandez, Christopher J; van der Meulen, Marjolein Ch

    2017-01-09

    Increases in fracture risk beyond what are expected from bone mineral density (BMD) are often attributed to poor "bone quality," such as impaired bone tissue strength. Recent studies, however, have highlighted the importance of tissue material properties other than strength, such as fracture toughness. Here we review the concepts behind failure properties other than strength and the physical mechanisms through which they cause mechanical failure: strength describes failure from a single overload; fracture toughness describes failure from a modest load combined with a preexisting flaw or damage; and fatigue strength describes failure from thousands to millions of cycles of small loads. In bone, these distinct failure mechanisms appear to be more common in some clinical fractures than others. For example, wrist fractures are usually the result of a single overload, the failure mechanism dominated by bone strength, whereas spinal fractures are rarely the result of a single overload, implicating multiple loading cycles and increased importance of fatigue strength. The combination of tissue material properties and failure mechanisms that lead to fracture represent distinct mechanistic pathways, analogous to molecular pathways used to describe cell signaling. Understanding these distinct mechanistic pathways is necessary because some characteristics of bone tissue can increase fracture risk by impairing fracture toughness or fatigue strength without impairing bone tissue strength. Additionally, mechanistic pathways to failure associated with fracture toughness and fatigue involve multiple loading events over time, raising the possibility that a developing fracture could be detected and interrupted before overt failure of a bone. Over the past two decades there have been substantial advancements in fracture prevention by understanding bone strength and fractures caused by a single load, but if we are to improve fracture risk prevention beyond what is possible now, we must

  1. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Yibin Kang

    2016-06-01

    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  2. Therapy Effect: Impact on Bone Marrow Morphology.

    Science.gov (United States)

    Li, K David; Salama, Mohamed E

    2016-03-01

    This article highlights the most common morphologic features identified in the bone marrow after chemotherapy for hematologic malignancies, growth-stimulating agents, and specific targeted therapies. The key is to be aware of these changes while reviewing post-therapeutic bone marrow biopsies and to not mistake reactive patterns for neoplastic processes. In addition, given the development and prevalent use of targeted therapy, such as tyrosine kinase inhibitors and immune modulators, knowledge of drug-specific morphologic changes is required for proper bone marrow interpretation and diagnosis.

  3. Glutamate signalling in bone.

    Directory of Open Access Journals (Sweden)

    Karen eBrakspear

    2012-08-01

    Full Text Available Mechanical loading plays a key role in the physiology of bone, allowing bone to functionally adapt to its environment, however characterisation of the signalling events linking load to bone formation is incomplete. A screen for genes associated with mechanical load-induced bone formation identified the glutamate transporter GLAST, implicating the excitatory amino acid, glutamate, in the mechanoresponse. When an osteogenic load (10N, 10Hz was externally applied to the rat ulna, GLAST (EAAT1 mRNA, was significantly down-regulated in osteocytes in the loaded limb. Functional components from each stage of the glutamate signalling pathway have since been identified within bone, including proteins necessary for calcium-mediated glutamate exocytosis, receptors, transporters and signal propagation. Activation of ionotropic glutamate receptors has been shown to regulate the phenotype of osteoblasts and osteoclasts in vitro and bone mass in vivo. Furthermore, glutamatergic nerves have been identified in the vicinity of bone cells expressing glutamate receptors in vivo. However, it is not yet known how a glutamate signalling event is initiated in bone or its physiological significance. This review will examine the role of the glutamate signalling pathway in bone, with emphasis on the functions of glutamate transporters in osteoblasts.

  4. Blood: bone equilibrium

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, M.W.

    1982-01-01

    The conundrum of blood undersaturation with respect to bone mineralization and its supersaturation with respect to bone's homeostatic function has acquired a new equation. On the supply side, Ca/sup 2 +/ is pumped in across bone cells to provide the needed Ca/sup 2 +/ x P/sub i/ for brushite precipitation. On the demand side, blood is in equilibrium with bone fluid, which is in equilibrium with a mineral more soluble than apatite. The function of potassium in this equation is yet to be found.

  5. Olecranon bone graft: revisited.

    Science.gov (United States)

    Mersa, Berkan; Ozcelik, Ismail Bulent; Kabakas, Fatih; Sacak, Bulent; Aydin, Atakan

    2010-09-01

    Autogenous bone grafts are frequently in use in the field of reconstructive upper extremity surgery. Cancellous bone grafts are applied to traumatic osseous defects, nonunions, defects after the resection of benign bone tumors, arthrodesis, and osteotomy procedures. Cancellous bone grafts do not only have benefits such as rapid revascularization, but they also have mechanical advantages. Despite the proximity to the primary surgical field, cancellous olecranon grafts have not gained the popularity they deserve in the field of reconstructive hand surgery. In this study, the properties, advantages, and technical details of harvesting cancellous olecranon grafts are discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-15

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

  7. Experimental Comparison of Cranial Particulate Bone Graft, rhBMP-2, and Split Cranial Bone Graft for Inlay Cranioplasty.

    Science.gov (United States)

    Hassanein, Aladdin H; Couto, Rafael A; Kurek, Kyle C; Rogers, Gary F; Mulliken, John B; Greene, Arin K

    2013-05-01

    Background :  Particulate bone graft and recombinant human bone morphogenetic protein-2 (rhBMP-2) are options for inlay cranioplasty in children who have not developed a diploic space. The purpose of this study was to determine whether particulate bone graft or rhBMP-2 has superior efficacy for inlay cranioplasty and to compare these substances to split cranial bone. Methods :  A 17 mm × 17 mm critical-sized defect was made in the parietal bones of 22 rabbits and managed in four ways: Group I (no implant; n=5), Group II (particulate bone graft; n=5), Group III (rhBMP-2; n=7), and Group IV (split cranial bone graft; n=5). Animals underwent microcomputed tomography and histologic analysis 16 weeks after cranioplasty. Results :  Defects without an implant (Group I) demonstrated inferior ossification (41.4%; interquartile range [IQR], 28.9% to 42.5%) compared to those treated with particulate bone graft (Group II: 99.5%; IQR, 97.8% to 100%), rhBMP-2 (Group III: 99.6%; IQR, 99.5% to 100%), or split cranial bone (Group IV: 100%) (P inlay calvarial defect areas equally, although the thickness of bone healed with rhBMP-2 is inferior. Clinically, particulate bone graft or split cranial bone graft may be superior to rhBMP-2 for inlay cranioplasty.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  9. Chondromodulin I Is a Bone Remodeling Factor

    Science.gov (United States)

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

    2003-01-01

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

  10. Development of a quantitative Real-Time PCR for micrometastasis detection using CEA in peripheral blood and bone marrow specimens of gastric cancer patients

    Directory of Open Access Journals (Sweden)

    Dardaei Alghalandis L

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Gastric adenocarsinoma is the first leading fatal malignancy in Iran. Despite advances in novel therapeutics approaches for gastric cancer (GC patient, tumor dissemination via blood stream to distant organ is still the major cause of death. Therefore, there is urgent need to establish sensitive methods for early detection of disseminated tumor cells in peripheral blood (PB and bone marrow (BM specimens of gastric cancer patients. "n"nMethods: In the present study, we use Carcinoma Embryonic Antigen (CEA as a tumor marker and Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH as an internal control to detection and quantification of disseminated tumor cells in PB and BM specimens of affected individuals. Total RNA was extracted from AGS (gastric cancer cell line and CEA and GAPDH fragments were generated by reverse transcription. The amplified fragments were cloned into pTZ57R/T vector separately. Double cloning of these genes has done into one pTZ57R/T vector. Serial dilution of this recombinant plasmid is used to construct standard curve, each containing a known amount of input copy number. Total RNA was extracted from BP and BM specimens of 35 GC patients. cDNA of the specimens were synthesized by reverse

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

    Science.gov (United States)

    Pennline, James; Mulugeta, Lealem

    2013-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur [1-3]. The most commonly used countermeasure against bone loss in microgravity has been prescribed exercise [4]. However, data has shown that existing exercise countermeasures are not as effective as desired for preventing bone loss in long duration, 4 to 6 months, spaceflight [1,3,5,6]. This spaceflight related bone loss may cause early onset of osteoporosis to place the astronauts at greater risk of fracture later in their lives. Consequently, NASA seeks to have improved understanding of the mechanisms of bone demineralization in microgravity in order to appropriately quantify this risk, and to establish appropriate countermeasures [7]. In this light, NASA's Digital Astronaut Project (DAP) is working with the NASA Bone Discipline Lead to implement well-validated computational models to help predict and assess bone loss during spaceflight, and enhance exercise countermeasure development. More specifically, computational modeling is proposed as a way to augment bone research and exercise countermeasure development to target weight-bearing skeletal sites that are most susceptible to bone loss in microgravity, and thus at higher risk for fracture. Given that hip fractures can be debilitating, the initial model development focused on the femoral neck. Future efforts will focus on including other key load bearing bone sites such as the greater trochanter, lower lumbar, proximal femur and calcaneus. The DAP has currently established an initial model (Beta Version) of bone loss due to skeletal unloading in femoral neck region. The model calculates changes in mineralized volume fraction of bone in this segment and relates it to changes in bone mineral density (vBMD) measured by Quantitative Computed Tomography (QCT). The model is governed by equations describing changes in bone volume fraction (BVF), and rates of

  12. Bone X-Ray (Radiography)

    Medline Plus

    Full Text Available ... ionizing radiation to produce pictures of any bone in the body. It is commonly used to diagnose ... bone x-ray makes images of any bone in the body, including the hand, wrist, arm, elbow, ...

  13. Bone X-Ray (Radiography)

    Medline Plus

    Full Text Available ... the body. X-rays are the oldest and most frequently used form of medical imaging. A bone ... bones. top of page How should I prepare? Most bone x-rays require no special preparation. You ...

  14. Effects of osteoporosis therapies on bone biomechanics

    OpenAIRE

    2010-01-01

    Anti-fracture therapies for the treatment of osteoporosis have been shown clinically to reduce the incidence of fracture; however, standard clinical measurements of bone density cannot sufficiently explain these large reductions. Therefore, the overall goal of this research is to develop a better understanding of the mechanisms through which anti-fracture therapies improve bone strength -- a critical determinant of fracture risk -- which should lead to improved assessment of treatment efficac...

  15. Imaging innovations in temporal bone disorders.

    Science.gov (United States)

    Corrales, C Eduardo; Fischbein, Nancy; Jackler, Robert K

    2015-04-01

    The development of new imaging techniques coupled with new treatment algorithms has created new possibilities in treating temporal bone diseases. This article provides an overview of recent imaging innovations that can be applied to temporal bone diseases. Topics covered include the role of magnetic resonance (MR) diffusion-weighted imaging in cholesteatomas and skull base epidermoids, whole-body molecular imaging in paragangliomas of the jugular foramen, and MR arterial spin labeling perfusion for dural arteriovenous fistulas and arteriovenous malformations.

  16. Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area.

    Science.gov (United States)

    Watanabe, Satoko; Takabatake, Kiyofumi; Tsujigiwa, Hidetsugu; Watanabe, Toshiyuki; Tokuyama, Eijiro; Ito, Satoshi; Nagatsuka, Hitoshi; Kimata, Yoshihiro

    2016-01-01

    Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb β-tricalcium phosphate (β-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb β-TCP (hole-diameter: 75, 300, 500, and 1600 μm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the β-TCP with hole-diameter 300μm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by β-TCP. Also, in zygomatic bone defect model with honeycomb β-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and β-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb β-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications.

  17. Brown Tumor Shown Flare Phenomenon On Bone Scan After Parathyroidectomy

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwang Ho; Park, Seol Hoon; Baek, So Ra; Chae, Sun Young; Koh, Jung Min; Kim, Jae Seung; Moon, Dae Hyuk; Ryu, Jin Sook [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2009-10-15

    Brown tumor is the benign bone lesion consists of woven bone and fibrous tissue without matrix, which develop due to chronic excessive osteoclastic activity such as hyperparathyroidism. Usually they appear with normal uptake or occasionally focally increased uptake on bone scan. We present a case with brown tumor shown more increased uptake and more number of lesions on bone scan after parathyroidectomy, and lesser increased uptake on serial bone scans without any other treatment through several months. This finding is thought to be similar to 'flare phenomenon' which is occasionally seen after treatment of metastatic bone lesions of malignant cancer, and may represent curative process of brown tumor with rapid normal bone formation.

  18. Children's bone health

    NARCIS (Netherlands)

    I.M. van der Sluis (Inge)

    2002-01-01

    textabstractThe thesis can be divided in two main parts. In the first part (Chapter 2 to 5) bone mineral density, bone metabolism and body composition in healthy children and young adults have been evaluated, while in the second part (Chapter 6 to 10) these issues were studied in children with vario

  19. Biodegradable synthetic bone composites

    Science.gov (United States)

    Liu, Gao; Zhao, Dacheng; Saiz, Eduardo; Tomsia, Antoni P.

    2013-01-01

    The invention provides for a biodegradable synthetic bone composition comprising a biodegradable hydrogel polymer scaffold comprising a plurality of hydrolytically unstable linkages, and an inorganic component; such as a biodegradable poly(hydroxyethylmethacrylate)/hydroxyapatite (pHEMA/HA) hydrogel composite possessing mineral content approximately that of human bone.

  20. Osteotransductive bone cements.

    Science.gov (United States)

    Driessens, F C; Planell, J A; Boltong, M G; Khairoun, I; Ginebra, M P

    1998-01-01

    Calcium phosphate bone cements (CPBCs) are osteotransductive, i.e. after implantation in bone they are transformed into new bone tissue. Furthermore, due to the fact that they are mouldable, their osteointegration is immediate. Their chemistry has been established previously. Some CPBCs contain amorphous calcium phosphate (ACP) and set by a sol-gel transition. The others are crystalline and can give as the reaction product dicalcium phosphate dihydrate (DCPD), calcium-deficient hydroxyapatite (CDHA), carbonated apatite (CA) or hydroxyapatite (HA). Mixed-type gypsum-DCPD cements are also described. In vivo rates of osteotransduction vary as follows: gypsum-DCPD > DCPD > CDHA approximately CA > HA. The osteotransduction of CDHA-type cements may be increased by adding dicalcium phosphate anhydrous (DCP) and/or CaCO3 to the cement powder. CPBCs can be used for healing of bone defects, bone augmentation and bone reconstruction. Incorporation of drugs like antibiotics and bone morphogenetic protein is envisaged. Load-bearing applications are allowed for CHDA-type, CA-type and HA-type CPBCs as they have a higher compressive strength than human trabecular bone (10 MPa).

  1. Pseudoanaplastic tumors of bone

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [Uijongbu St. Mary Hospital, The Catholic University of Korea, Department of Orthopaedic Surgery, Gyunggido, 480-821 (Korea); Mirra, Joseph M. [Orthopaedic Hospital, Orthopedic Oncology, Los Angeles, California (United States)

    2004-11-01

    To discuss the concept of pseudoanaplastic tumors of bone, which pathologically show hyperchromatism and marked pleomorphism with quite enlarged, pleomorphic nuclei, but with no to extremely rare, typical mitoses, and to propose guidelines for their diagnosis. From a database of 4,262 bone tumors covering from 1971 to 2001, 15 cases of pseudoanaplastic bone tumors (0.35% of total) were retrieved for clinical, radiographic and pathologic review. Postoperative follow-up after surgical treatment was at least 3 years and a maximum of 7 years. There were eight male and seven female patients. Their ages ranged from 10 to 64 years with average of 29.7 years. Pathologic diagnoses of pseudoanaplastic variants of benign bone tumors included: osteoblastoma (4 cases), giant cell tumor (4 cases), chondromyxoid fibroma (3 cases), fibrous dysplasia (2 cases), fibrous cortical defect (1 case) and aneurysmal bone cyst (1 case). Radiography of all cases showed features of a benign bone lesion. Six cases, one case each of osteoblastoma, fibrous dysplasia, aneurysmal bone cyst, chondromyxoid fibroma, giant cell tumor and osteoblastoma, were initially misdiagnosed as osteosarcoma. The remaining cases were referred for a second opinion to rule out sarcoma. Despite the presence of significant cytologic aberrations, none of our cases showed malignant behavior following simple curettage or removal of bony lesions. Our observation justifies the concept of pseudoanaplasia in some benign bone tumors as in benign soft tissue tumors, especially in their late evolutionary stage when bizarre cytologic alterations strongly mimic a sarcoma. (orig.)

  2. 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.

  3. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    Directory of Open Access Journals (Sweden)

    Quarto Rodolfo

    2010-01-01

    Full Text Available Abstract Background Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. Methods We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. Results At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. Conclusions We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

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

    Science.gov (United States)

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

    2016-12-01

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

  5. The effects of bone marrow aspirate, bone graft, and collagen composites on fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Sandri, Monica

    2012-01-01

    contamination, and non union as well as the potential risk of disease transmission. Hydroxyapatite and collagen composites (HA/Collagen) have the potential in mimicking and replacing skeletal bones. This study attempted to determine the effects of newly developed HA/Collagen-composites with and without bone...... marrow aspirate (BMA) on enhancement of bone implant fixation. Method: Titanium alloy implants were inserted into bilateral femoral condyles of eight skeletally mature sheep, four implants per sheep. The implant had a circumferential gap of 2 mm. The gap was filled with: HA/Collagen; HA/Collagen...... and histomorphometry between autograft and allograft groups. The implants in both the HA/Collagen and HA/Collagen-BMA groups were mostly surrounded by fibrous tissue. Thus, mechanical testing of these samples was impossible. The histomorphometry results showed significantly more new bone and bone ongrowth...

  6. 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

    2016-07-05

    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.

  7. [Bone tissue engineering. Reconstruction of critical sized segmental bone defects in the ovine tibia].

    Science.gov (United States)

    Reichert, J C; Epari, D R; Wullschleger, M E; Berner, A; Saifzadeh, S; Nöth, U; Dickinson, I C; Schuetz, M A; Hutmacher, D W

    2012-04-01

    Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds.Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

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

    Science.gov (United States)

    Pennline, James A.

    2009-01-01

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

  9. Osteogenesis and angiogenesis: The potential for engineering bone

    Directory of Open Access Journals (Sweden)

    JM Kanczler

    2008-05-01

    Full Text Available The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic or implants (polymeric or metallic. These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue.The engineering of bone tissue offers new therapeutic strategies to aid musculoskeletal healing. Various scaffold constructs have been employed in the development of tissue-engineered bone; however, an active blood vessel network is an essential pre-requisite for these to survive and integrate with existing host tissue. Combination therapies of stem cells and polymeric growth factor release scaffolds tailored to promote angiogenesis and osteogenesis are under evaluation and development actively to stimulate bone regeneration. An understanding of the cellular and molecular interactions of blood vessels and bone cells will enhance and aid the successful development of future vascularised bone scaffold constructs, enabling survival and integration of bioengineered bone with the host tissue. The role of angiogenic and osteogenic factors in the adaptive response and interaction of osteoblasts and endothelial cells during the multi step process of bone development and repair will be highlighted in this review, with consideration of how some of these key mechanisms can be combined with new developments in tissue engineering to enable repair and growth of skeletal fractures. Elucidation of the processes of angiogenesis, osteogenesis and tissue engineering strategies offer

  10. Quick and inexpensive paraffin-embedding method for dynamic bone formation analyses

    Science.gov (United States)

    Porter, Amy; Irwin, Regina; Miller, Josselyn; Horan, Daniel J.; Robling, Alexander G.; McCabe, Laura R.

    2017-01-01

    We have developed a straightforward method that uses paraffin-embedded bone for undemineralized thin sectioning, which is amenable to subsequent dynamic bone formation measurements. Bone has stiffer material properties than paraffin, and therefore has hereforto usually been embedded in plastic blocks, cured and sectioned with a tungsten carbide knife to obtain mineralized bone sections for dynamic bone formation measures. This process is expensive and requires special equipment, experienced personnel, and time for the plastic to penetrate the bone and cure. Our method utilizes a novel way to prepare mineralized bone that increases its compliance so that it can be embedded and easily section in paraffin blocks. The approach is simple, quick, and costs less than 10% of the price for plastic embedded bone sections. While not effective for static bone measures, this method allows dynamic bone analyses to be readily performed in laboratories worldwide which might not otherwise have access to traditional (plastic) equipment and expertise. PMID:28198415

  11. A study of stress-free living bone and its application to space flight

    Science.gov (United States)

    Leblanc, A.; Spira, M.

    1983-01-01

    Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

  12. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun [Department of Ophthalmology, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Liu Guangpeng [Key Laboratory of Tissue Engineering, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhang Peng [Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science (China); Hou Hongliang; Tang Tingting, E-mail: drfanxianqun@126.com [Department of Orthopedics, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China)

    2011-02-15

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  13. Distal radius bone mineral density estimation using the filling factor of trabecular bone in the x-ray image.

    Science.gov (United States)

    Lee, Sooyeul; Jeong, Ji-Wook; Lee, Jeong Won; Yoo, Done-Sik; Kim, Seunghwan

    2006-01-01

    Osteoporosis is characterized by an abnormal loss of bone mineral content, which leads to a tendency to non-traumatic bone fractures or to structural deformations of bone. Thus, bone density measurement has been considered as a most reliable method to assess bone fracture risk due to osteoporosis. In past decades, X-ray images have been studied in connection with the bone mineral density estimation. However, the estimated bone mineral density from the X-ray image can undergo a relatively large accuracy or precision error. The most relevant origin of the accuracy or precision error may be unstable X-ray image acquisition condition. Thus, we focus our attentions on finding a bone mineral density estimation method that is relatively insensitive to the X-ray image acquisition condition. In this paper, we develop a simple technique for distal radius bone mineral density estimation using the trabecular bone filling factor in the X-ray image and apply the technique to the wrist X-ray images of 20 women. Estimated bone mineral density shows a high linear correlation with a dual-energy X-ray absorptiometry (r=0.87).

  14. [THE IMPORTANCE OF "MILK BONES" TO "WISDOM BONES" - COW MILK AND BONE HEALTH - LESSONS FROM MILK ALLERGY PATIENTS].

    Science.gov (United States)

    Nachshon, Liat; Katz, Yitzhak

    2016-03-01

    The necessity of milk consumption in the western diet is a subject of intense controversy. One of the main benefits of milk is that it is the main source of dietary calcium. Calcium is a major bone mineral, mandatory for bone health. Its supply is derived exclusively from external dietary sources. During the growth period, an increased calcium supply is needed for the process of bone mass accumulation. An optimal bone mass achieved by the end of the growth period may be protective later in life against the bone mass loss that commonly occurs. This in turn, can be preventative against the occurrence of osteoporosis and the development of spontaneous bone fractures. Over the past several decades, an increased incidence of osteoporosis has been documented in western countries, leading to high rates of morbidity and mortality in the middle-aged and geriatric population. Many studies have investigated the dietary calcium requirements for different ages, to achieve and maintain proper bone health. Based on their results, guidelines concerning calcium intake in every stage of life have been published by national and international organizations. In the western diet, it is difficult to achieve the recommended calcium intake without milk consumption. Moreover, calcium bioavailability for intestinal absorption is high. Several studies have recently raised doubts concerning the amounts of calcium intake in the western diet and its effectiveness in preventing osteoporosis. The main disadvantage of these studies is their being based on the patient's past memory recall of milk consumption. Patients with IgE-mediated cow's milk protein allergy are a unique population. Their lifetime negligible milk consumption is undisputed. A recent study investigated for the first time, the bone density of young adults with milk allergy at the end of their growth period. Their severe reduction in bone mineral density and dietary calcium intake defines them as a high risk group for the

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  16. Perfluorodecalin and bone regeneration

    Directory of Open Access Journals (Sweden)

    F Tamimi

    2013-01-01

    Full Text Available Perfluorodecalin (PFD is a chemically and biologically inert biomaterial and, as many perfluorocarbons, is also hydrophobic, radiopaque and has a high solute capacity for gases such as oxygen. In this article we have demonstrated, both in vitro and in vivo, that PFD may significantly enhance bone regeneration. Firstly, the potential benefit of PFD was demonstrated by prolonging the survival of bone marrow cells cultured in anaerobic conditions. These findings translated in vivo, where PFD incorporated into bone-marrow-loaded 3D-printed scaffolds substantially improved their capacity to regenerate bone. Secondly, in addition to biological applications, we have also shown that PFD improves the radiopacity of bone regeneration biomaterials, a key feature required for the visualisation of biomaterials during and after surgical implantation. Finally, we have shown how the extreme hydrophobicity of PFD enables the fabrication of highly cohesive self-setting injectable biomaterials for bone regeneration. In conclusion, perfluorocarbons would appear to be highly beneficial additives to a number of regenerative biomaterials, especially those for bone regeneration.

  17. CHARCOAL PACKED FURNACE FOR LOW-TECH CHARRING OF BONE

    DEFF Research Database (Denmark)

    Jacobsen, P.; Dahi, Elian

    1997-01-01

    A low-tech furnace for charring of raw bone using char coal is developed and tested. The furnace consists of a standard oil drum, fitted with simple materials as available in every market in small towns in developing counties. 80 kg of raw bone and 6 kg of charcoal are used for production of 50 k...

  18. Nutrition in bone health revisited: a story beyond calcium.

    Science.gov (United States)

    Ilich, J Z; Kerstetter, J E

    2000-01-01

    Osteoporosis is a complex, multi-factorial condition characterized by reduced bone mass and impaired micro-architectural structure, leading to an increased susceptibility to fractures. Although most of the bone strength (including bone mass and quality) is genetically determined, many other factors (nutritional, environmental and life-style) also influence bone. Nutrition is important modifiable factor in the development and maintenance of bone mass and the prevention and treatment of osteoporosis. Approximately 80-90% of bone mineral content is comprised of calcium and phosphorus. Other dietary components, such as protein, magnesium, zinc, copper, iron, fluoride, vitamins D, A, C, and K are required for normal bone metabolism, while other ingested compounds not usually categorized as nutrients (e.g. caffeine, alcohol, phytoestrogens) may also impact bone health. Unraveling the interaction between different factors; nutritional, environmental, life style, and heredity help us to understand the complexity of the development of osteoporosis and subsequent fractures. This paper reviews the role of dietary components on bone health throughout different stages of life. Each nutrient is discussed separately, however the fact that many nutrients are co-dependent and simultaneously interact with genetic and environmental factors should not be neglected. The complexity of the interactions is probably the reason why there are controversial or inconsistent findings regarding the contribution of a single or a group of nutrients in bone health.

  19. The Bone-Muscle Relationship in Men and Women

    Directory of Open Access Journals (Sweden)

    Thomas F. Lang

    2011-01-01

    Full Text Available Muscle forces are a strong determinant of bone structure, particularly during the process of growth and development. The gender divergence in the bone-muscle relationship becomes strongly evident during adolescence. In females, growth is characterized by increased estrogen levels and increased mass and strength of bone relative to that of muscle, whereas in men, increases in testosterone fuel large increases in muscle, resulting in muscle forces that coincide with a large growth in bone dimensions and strength. In adulthood, significant age-related losses are observed for both bone and muscle tissues. Large decrease in estrogen levels in women appears to diminish the skeleton's responsiveness to exercise more than in men. In contrast, the aging of the muscle-bone axis in men is a function of age related declines in both hormones. In addition to the well-known age related changes in the mechanical loading of bone by muscle, newer studies appear to provide evidence of age- and gender-related variations in molecular signaling between bone and muscle that are independent of purely mechanical interactions. In summary, gender differences in the acquisition and age-related loss in bone and muscle tissues may be important for developing gender-specific strategies for using exercise to reduce bone loss with aging.

  20. Acidosis, hypoxia and bone.

    Science.gov (United States)

    Arnett, Timothy R

    2010-11-01

    Bone homeostasis is profoundly affected by local pH and oxygen tension. It has long been recognised that the skeleton contains a large reserve of alkaline mineral (hydroxyapatite), which is ultimately available to neutralise metabolic H(+) if acid-base balance is not maintained within narrow limits. Bone cells are extremely sensitive to the direct effects of pH: acidosis inhibits mineral deposition by osteoblasts but it activates osteoclasts to resorb bone and other mineralised tissues. These reciprocal responses act to maximise the availability of OH(-) ions from hydroxyapatite in solution, where they can buffer excess H(+). The mechanisms by which bone cells sense small pH changes are likely to be complex, involving ion channels and receptors in the cell membrane, as well as direct intracellular effects. The importance of oxygen tension in the skeleton has also long been known. Recent work shows that hypoxia blocks the growth and differentiation of osteoblasts (and thus bone formation), whilst strongly stimulating osteoclast formation (and thus bone resorption). Surprisingly, the resorptive function of osteoclasts is unimpaired in hypoxia. In vivo, tissue hypoxia is usually accompanied by acidosis due to reduced vascular perfusion and increased glycolytic metabolism. Thus, disruption of the blood supply can engender a multiple negative impact on bone via the direct actions of reduced pO(2) and pH on bone cells. These observations may contribute to our understanding of the bone disturbances that occur in numerous settings, including ageing, inflammation, fractures, tumours, anaemias, kidney disease, diabetes, respiratory disease and smoking.

  1. 鼠哺乳期二(噁)英暴露对子代牙槽骨生长发育的影响%Effects of lactational dioxin exposure to development of alveolar bone in SD rat offspring

    Institute of Scientific and Technical Information of China (English)

    耿华欧; 章锦才; 胡彬; 王京滨

    2008-01-01

    目的 研究鼠哺乳期二(噁)英类物质2,3,7,8-四氯二苯对二(噁)英暴露对大鼠仔鼠牙槽骨生长发育的影响.方法 60天龄2,3,7,8-四氯二苯对二(噁)英暴露组和对照组仔大鼠被处死,将其带有磨牙的上颌骨行树脂包埋,制备硬组织磨片并在荧光显微镜下观察,对两实验组牙槽骨的组织形态、荧光标记情况及组织形态计量学参数进行比较.结果 与对照组相比,二(噁)英暴露组牙槽骨骨小梁结构较为疏松,荧光标记较紊乱.实验组与对照组骨小梁宽度分别为(52.5±5.2)μm及(59.4±6.6)μm,二者差异有统计学意义(P<0.05);骨小梁数目分别为(3.27±0.23)mm-1及(3.75±0.29)mm-1,差异有统计学意义(P<0.01);骨小梁分离度分别为(217.3±37.6)μm及(177.6±33.8)μm,差异有统计学意义(P<0.05);矿化沉积率分别为(0.68±0.08)μm/d及(0.95±0.12)μm/d,差异亦有统计学意义(P<0.05).结论 二(噁)英类物质哺乳期暴露显著降低了大鼠仔鼠牙槽骨的质、量,并影响其空间构型.%Objective To study the influence of lactational dioxin exposure(2,3,7,8-tetrachlorodibenzo-p-dixon,TCDD)on development of alveolar bone in SD rat offspring.Methods The rats of TCDD exposure group and control group were sacrificed and the alveolar bone with molars of PD60 rats in the two groups were embedded in resin.The sections were observed by fluorescent microscope.The alveolar bone formation was evaluated by histological examination,tetracycline fluorescence marker and quantitative histomorphometry.The indices of quantitative histomorphometry were compaired.Resuits The trabecular structure of abeolar bone was looser in TCDD exposure group than in the control group.The tetracycline fluorescence markers were more disorganized in TCDD group.The indices of quantitative histomorphometry of alveolar bone between two groups showed significantly difierent. Conclusions Lactational 2,3,7,8-TCDD exposure decreased the quality and quantity of

  2. Prostate cancer cells metastasize to the hematopoietic stem cell niche in bone

    Institute of Scientific and Technical Information of China (English)

    Evan T Keller

    2011-01-01

    @@ The majority of men with advanced prostate cancer develop bone metastases as opposed to metastases at other sites.1 It has been unclear why prostate cancer selectively metastasizes to and proliferates in bone.Recently, Shiozawa et al.Delineated a mechanism that may account for the establishment of prostate cancer in bone.2 Specifically, they identified that prostate cancer cells compete with hematopoietic stem cells (HSC) for the osteoblast in the HSC niche of the bone.Defining the mechanisms through which prostate cancer cells establish themselves in bone is critical towards developing effective therapeutic strategies to prevent or target bone metastases.

  3. Pregnancy, Breastfeeding, and Bone Health

    Science.gov (United States)

    ... need for calcium. During pregnancy, women produce more estrogen, a hormone that protects bones. Any bone mass lost during pregnancy is typically ... mass during breastfeeding because they’re producing less estrogen, which is the hormone that protects bones. The good news is that, like bone lost ...

  4. Oral Health and Bone Disease

    Science.gov (United States)

    ... low bone mass. Research suggests a link between osteoporosis and bone loss in the jaw. The bone in the jaw supports and anchors the teeth. When the jawbone becomes less dense, tooth loss can occur, a common occurrence in older adults. Skeletal Bone Density and Dental Concerns Periodontal Disease ...

  5. Prolyl hydroxylase inhibitors protect from the bone loss in ovariectomy rats by increasing bone vascularity.

    Science.gov (United States)

    Liu, Xiaodong; Tu, Yihui; Zhang, Lianfang; Qi, Jin; Ma, Tong; Deng, Lianfu

    2014-05-01

    The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway is involved in skeletal development, bone repair, and postmenopausal osteoporosis. Inhibitors of prolyl hydroxylases (PHD) enhance vascularity, increase callus formation in a stabilized fracture model, and activate the HIF-1α/VEGF pathway. This study examined the effects of estrogen on the HIF-1α/VEGF pathway in osteoblasts and whether PHD inhibitors can protect from bone loss in postmenopausal osteoporosis. Osteoblasts were treated with estrogen, and expressions of HIF-1α and VEGF were measured at mRNA (qPCR) and protein (Western blot) levels. Further, osteoblasts were treated with inhibitors of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, and levels of VEGF mRNA and protein expression were detected. In addition, ovariectomized rats were treated with PHD inhibitors, and bone microarchitecture and bone mechanical strength were assessed using micro-CT and biomechanical analyses (lower ultimate stress, modulus, and stiffness). Blood vessel formation was measured with India Ink Perfusion and immunohistochemistry. Estrogen, in a dose- and time-dependent manner, induced VEGF expression at both mRNA and protein levels and enhanced HIF-1α protein stability. Further, the estrogen-induced VEGF expression in osteoblasts involved the PI3K/Akt pathway. PHD inhibitors increased bone mineral density, bone microarchitecture and bone mechanical strength, and promoted blood vessel formation in ovariectomized rats. In conclusion, estrogen and PHD inhibitors activate the HIF-1α/VEGF pathway in osteoblasts. PHD inhibitors can be utilized to protect bone loss in postmenopausal osteoporosis by improving bone vascularity and angiogenesis in bone marrow.

  6. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2.

    Science.gov (United States)

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn; O'Connor, J Patrick

    2015-07-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.

  7. Osteopetrosis (marble bone disease

    Directory of Open Access Journals (Sweden)

    Alexey Nikolayevich Kalyagin

    2014-01-01

    Full Text Available We report the data of the history of describing osteopetrosis (marble bone disease, its clinical features, diagnosis, and possible therapy approaches. Our own clinical case is presented.

  8. Petrous Bone Cholesteatoma

    Science.gov (United States)

    Sanna, Mario; Zini, Carlo; Gamoletti, Roberto; Frau, Niccolò; Taibah, Abdel Kader; Russo, Alessandra; Pasanisi, Enrico

    1993-01-01

    Petrous bone cholesteatoma is a rare pathologic entity and may be a difficult surgical challenge because of potential involvement of the facial nerve, carotid artery, dura mater, otic capsule, and risk of cerebrospinal fluid leak. The objective of this article is to present a personal classification of petrous bone cholesteatomas, a survey of recent surgical attitudes, and our present surgical strategy based on our experience with 54 operations between 1978 and 1990. Radical petromastoid exenteration with marsupialization and the middle cranial fossa approach were used only for small pure infra- or supralabyrinthine cholesteatomas, respectively. The enlarged transcochlear approach with closure of the external auditory canal was used for infralabyrinthine, infralabyrinthine-apical, and massive petrous bone cholesteatomas. Five cases with petrous bone cholesteatomas in different locations are described in detail to present the signs and symptoms together with the management. ImagesFigure 10Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16Figure 17Figure 18 PMID:17170912

  9. Metastatic Bone Disease

    Science.gov (United States)

    ... begin in bone are much less common in adults older than 45 years. Other diseases, such as Paget’s sarcoma, post-radiation sarcoma, hyperparathyroidism, and fractures due to osteoporosis, are also possibilities. Additional tests will likely be ...

  10. Collagen for bone tissue regeneration.

    Science.gov (United States)

    Ferreira, Ana Marina; Gentile, Piergiorgio; Chiono, Valeria; Ciardelli, Gianluca

    2012-09-01

    In the last decades, increased knowledge about the organization, structure and properties of collagen (particularly concerning interactions between cells and collagen-based materials) has inspired scientists and engineers to design innovative collagen-based biomaterials and to develop novel tissue-engineering products. The design of resorbable collagen-based medical implants requires understanding the tissue/organ anatomy and biological function as well as the role of collagen's physicochemical properties and structure in tissue/organ regeneration. Bone is a complex tissue that plays a critical role in diverse metabolic processes mediated by calcium delivery as well as in hematopoiesis whilst maintaining skeleton strength. A wide variety of collagen-based scaffolds have been proposed for different tissue engineering applications. These scaffolds are designed to promote a biological response, such as cell interaction, and to work as artificial biomimetic extracellular matrices that guide tissue regeneration. This paper critically reviews the current understanding of the complex hierarchical structure and properties of native collagen molecules, and describes the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of innovative techniques for scaffold and material manufacturing that are currently opening the way to the preparation of biomimetic substrates that modulate cell interaction for improved substitution, restoration, retention or enhancement of bone tissue function.

  11. SHEEP TEMPORAL BONE

    Directory of Open Access Journals (Sweden)

    Kesavan

    2016-03-01

    Full Text Available INTRODUCTION Human temporal bones are difficult to procure now a days due to various ethical issues. Sheep temporal bone is a good alternative due to morphological similarities, easy to procure and less cost. Many middle ear exercises can be done easily and handling of instruments is done in the procedures like myringoplasty, tympanoplasty, stapedotomy, facial nerve dissection and some middle ear implants. This is useful for resident training programme.

  12. Bone changes in leprosy

    Energy Technology Data Exchange (ETDEWEB)

    Mende, B.; Stein, G.; Kreysel, H.W.

    1985-02-01

    Bone lesions is a frequent organic manifestation in leprosy. Osseal destructions caused by granulomatous process induced by M. leprae are so-called specific lesions in contrast to non specific lesions based on nerval or arterial diseases. The specific osseal alterations are characterized by cystic brightenings in roentgenograms while non specific osseal changes show absorption to bone structure as akroosterolysis and osteoporosis. Typical radiologic findings in different stages of mutilation are demonstrated.

  13. Therapy for bone metastasis from different cancers

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhang; Peng Tan; Baoguo Mi; Chao Song; Yi Deng; Hanfeng Guan

    2016-01-01

    The bone is the most common target organ of cancer metastasis. Bone metastasis leads to considerable morbidity due to skeletal-related events (SREs). These include bone pain, hypercalcemia, pathologic frac-tures, and compression of the spinal cord. Cancers such as those of the lung, breast, prostate, and kidney are more likely to cause SREs than other cancer types. Additionaly, some blood cancers, including multiple myeloma and lymphoma, frequently cause SREs. In this article, we review the conventional therapies for metastatic bone disease, including drug therapy, radiotherapy, and surgery. Among osteoclast-targeting agents, bisphosphonates and nuclear factor kappa-B ligand inhibitors are the most widely used agents to prevent cancer-related bone loss. Unsealed radioisotopes are also considered promising in cancer therapy. Currently, iodine-131, strontium-89, and radium-223 are available for the treatment of bone metastasis. However, the treatments for blood cancers with SREs are diferent from those of other cancers. In those cases, new classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal anti-bodies, and histone deacetylase inhibitors have shown remarkable eficacy. We also discuss the potential development of new therapies for these diseases.

  14. Does simvastatin stimulate bone formation in vivo?

    Directory of Open Access Journals (Sweden)

    Chorev Michael

    2003-04-01

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

  15. Bone graft substitutes: past, present, future.

    Directory of Open Access Journals (Sweden)

    Parikh S

    2002-04-01

    Full Text Available Bone grafts are necessary to provide support, fill voids, and enhance biologic repair of skeletal defects. They are used by orthopaedic surgeons, neurosurgeons, craniofacial surgeons, and periodontists. Bone harvested from donor sites is the gold standard for this procedure. It is well documented that there are limitations and complications from the use of autograft, including the limited quantity and associated chronic donor site pain. Despite the increase in the number of procedures that require bone grafts, there has not been a single ideal bone graft substitute Scientists, surgeons, and medical companies, thus, have a tremendous responsibility to develop biologic alternatives that will enhance the functional capabilities of the bone graft substitute, and potentially reduce or eliminate the need for autograft. This article is an attempt to review the past and existing bone graft substitutes, and future directions of research. The historical data was extracted after thorough review of the literature. The data for the current concepts and future directions was compiled from the Internet, and from direct correspondence with medical companies. Since many products are undergoing clinical trials, and are yet not commercially available, their data cannot be found in literature. The main purpose of this article is to give the reader an idea about the existing market products and products likely to be available in near future.

  16. Inhibitory regulation of osteoclast bone resorption by signal regulatory protein alpha

    NARCIS (Netherlands)

    E.M. van Beek; T.J. de Vries; L. Mulder; T. Schoenmaker; K.A. Hoeben; T. Matozaki; G.E.J. Langenbach; G. Kraal; V. Everts; T.K. van den Berg

    2009-01-01

    Osteoclasts mediate bone resorption, which is critical for bone development, maintenance, and repair. Proper control of osteoclast development and function is important and deregulation of these processes may lead to bone disease, such as osteoporosis. Previous studies have shown that the cytosolic

  17. Gelation and biocompatibility of injectable alginate-calcium phosphate gels for bone regeneration

    NARCIS (Netherlands)

    Cardoso, D.A.; Beucken, J.J.J.P van den; Both, L.L.; Bender, J.; Jansen, J.A.; Leeuwenburgh, S.C.G.

    2014-01-01

    An emerging approach toward development of injectable, self-setting, and fully biodegradable bone substitutes involves the combination of injectable hydrogel matrices with a dispersed phase consisting of nanosized calcium phosphate particles. Here, novel injectable composites for bone regeneration h

  18. Effect of Microstructure on Fatigue Strength of Bovine Compact Bones

    Science.gov (United States)

    Kim, Jong Heon; Niinomi, Mitsuo; Akahori, Toshikazu; Takeda, Junji; Toda, Hiroyuki

    Despite its clinical importance in developing artificial bone, limited information is available regarding the microstructure with respect to the fatigue characteristics of bones. In this study, the fatigue characteristics of the bovine humerus and femur were investigated with respect to microstructures. Fatigue tests were conducted on the bovine humerus and femur at a stress ratio of 0.1 and a frequency of 10Hz. The fatigue strength of the plexiform bone is slightly greater than that of the haversian bone. This is because the volume fraction of voids in the haversian bone, which is the site of stress concentration, is higher than that of voids in the plexiform bone. Several microcracks are observed on the fatigue fracture surface of the haversian bone. The microcracks are short and their propagation directions are random. However, the number of the microcracks in the plexiform bone is very small. The microcracks are relatively long and their propagation directions are parallel to the longitudinal direction of the lamellar bone. Therefore, the crack requires relatively more energy to propagate across the lamella in the plexiform bone.

  19. Role of osteocytes in multiple myeloma bone disease

    Science.gov (United States)

    Delgado-Calle, Jesus; Bellido, Teresita; Roodman, G. David

    2014-01-01

    Purpose of review Despite the increased knowledge of osteocyte biology, the contribution of this most abundant bone cell to the development and progression of multiple myeloma in bone is practically unexplored. Recent findings Multiple myeloma bone disease is characterized by exacerbated bone resorption and the presence of osteolytic lesions that do not heal because of a concomitant reduction in bone formation. Osteocytes produce molecules that regulate both bone formation and resorption. Recent findings suggest that the life span of osteocytes is compromised in multiple myeloma patients with bone lesions. In addition, multiple myeloma cells affect the transcriptional profile of osteocytes by upregulating the production of pro-osteoclastogenic cytokines, stimulating osteoclast formation and activity. Further, patients with active multiple myeloma have elevated circulating levels of sclerostin, a potent inhibitor of bone formation which is specifically expressed by osteocytes in bone. Summary Understanding the contribution of osteocytes to the mechanisms underlying the skeletal consequences of multiple myeloma bone disease has the potential to provide important new therapeutic strategies that specifically target multiple myeloma–osteocyte interactions. PMID:25289928

  20. Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

    Science.gov (United States)

    Titorencu, Irina; Albu, Madalina Georgiana; Nemecz, Miruna; Jinga, Victor V

    2017-01-01

    The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered.

  1. DIAGNOSTICS OF BONE METABOLISM DISORDERS IN ONCOLOGICAL DISEASES

    Directory of Open Access Journals (Sweden)

    O. I. Apolikhin

    2015-01-01

    Full Text Available Osteoporosis is one of the most significant bone complications of cancer. About 1.5 million cancer patients worldwide have bone metastases. Patients with myeloma, breast cancer, prostate, thyroid, bladder and lung have very high risk of development of bone lesions and related complications. Currently, osteodensitometry is the gold standard for the diagnosis of osteoporosis. In recent years we frequently use the innovative imaging techniques for bone metastases, such as CT, MRI, PET/CT. Unfortunately, the diagnostic value of these methods is that it is not always possible to identify abnormalities of bone metabolism in cancer, especially in the early stages. This review shows the world experience of usage of biochemical markers of bone resorption (calcium, hydroxyproline, NTX, CTX, PYD, DPD, TRAP-5b, bone sialoprotein - BSP and markers of bone synthesis (osteocalcin, CSF, ACF, Karlovy vary IFF, their advantages and disadvantages. The level of these markers is increased in most patients with osteoporosis and bone metastases, it is suggesting a potential role in early diagnosis of bone metastases.

  2. System for the analysis of whole-bone strength from helical CT images

    Science.gov (United States)

    Camp, Jon J.; Karwoski, Ronald A.; Stacy, Mahlon C.; Atkinson, Elizabeth J.; Khosla, Sundeep; Melton, L. Joseph; Riggs, B. Lawrence; Robb, Richard A.

    2004-04-01

    Osteoporosis affects an estimated 44 million Americans. This condition results from bone loss, but the measured change in bone mass does not fully account for the marked decrease in whole-bone structural integrity seen in osteoporosis. In order to study structural changes in bone mineral distribution due to normal ageing and osteoporosis, we have developed a method for progressive analysis of whole-bone mechanical integrity from helical CT images. The system provides rapid semi-automated alignment of femur and vertebrae volume images into standard anatomic reference planes, and calculates bone mineral density in any selected 3D sections of bone. Mineral density measures are obtained using both full-width-half-max contours and threshold-derived masks, and are obtained for cortical bone and trabecular bone separately. Biomechanical properties of the bone cross-section are also assessed, including the 2-D bending moment of the cortical bone region and the integrated flexural rigidity of the cortical region or whole-bone region in arbitrary planes. This method facilitates progressive refinement of the analysis protocol by separating the labor-intensive alignment and landmark selection process from the analysis process. As the analysis protocol evolves to include new measures, previously analyzed images can be automatically reanalyzed, using the image regions originally specified. Initial results show inverse correlation of indices of biomechanical bone strength with age, greater loss of bone strength in the lumbar spine than in the femoral neck, and more trabecular than cortical bone loss at both sites.

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

    Science.gov (United States)

    Baek, Ki Hyun; Kang, Moo Il

    2009-01-01

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

  4. Handheld Fluorescence Resonance Energy Transfer (FRET)-Aptamer Sensor for Bone Markers

    Science.gov (United States)

    Bruno, John G.

    2015-01-01

    Astronauts lose significant bone mass during lengthy space flights. NASA wishes to monitor this bone loss in order to develop nutritional and exercise countermeasures. Operational Technologies Corporation (OpTech) has developed a handheld device that quantifies bone loss in a spacecraft environment. The innovation works by adding fluorescent dyes and quenchers to aptamers to enable pushbutton, one-step bind-and-detect FRET assays that can be freeze-dried, rehydrated with body fluids, and used to quantify bone loss.

  5. Development of a readily applied method to quantify ractopamine residue in meat and bone meal by QuEChERS-LC-MS/MS.

    Science.gov (United States)

    Gressler, Vanessa; Franzen, Angélica R L; de Lima, Gustavo J M M; Tavernari, Fernando C; Dalla Costa, Osmar A; Feddern, Vivian

    2016-03-15

    A QuEChERS method of ractopamine (RCT) residue detection in swine meat and bone meal (MBM) samples was demonstrated. Samples were hydrolyzed with protease and β-glucuronidase prior to QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction and clean-up. Samples were analyzed in a Liquid Chromatography (equipped with ACE 5 C18 column under gradient elution) coupled with a triple quadrupole mass spectrometer operating in positive electrospray ionization mode (using multiple reaction monitoring, MRM). The method was validated for its specificity, decision limit (CCα), detection capability (CCβ), recovery, repeatability, reproducibility, linearity, limits of detection (LODs), quantification (LOQs), and stability according to international guidelines (European Commission Decision 2002/657/EC). Recoveries ranged from 96.3 to 107.0%. Repeatability and reproducibility showed both RSD<5.7% and 3.1%, respectively. LODs and LOQs were 1.91 and 6.36 ppb, respectively. CCα and CCβ values were 1.91 and 2.37 ppb, respectively. RCT showed good stability for spiked samples and real samples when the concentration was higher, otherwise at lower concentration stability was lower. The proposed method can be successfully applied on a regular basis for the determination of RCT in MBM, demonstrating the usefulness of the method as a tool for compliance monitoring in regulatory laboratories.

  6. 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

  7. MicroCT evaluation of bone mineral density loss in human bones

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Liebert P.; Braz, Delson; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Lab. de Instrumentacao Nuclear]. E-mails: lnogueira@con.ufrj.br; Barroso, Regina C.; Oliveira, Luis F. [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: cely@uerj.br

    2007-07-01

    Bone is a connective tissue largely composed of an organic protein, collagen and the inorganic mineral hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}OH{sub 2}], which combine to provide a mechanical and supportive role in the body. Depending on the orientation of collagen fibers, two types of bone can be distinguished: trabecular and cortical bone. Degree of mineralization is considered an important feature of bone quality. Changes in the degree of mineralization is generally due to osteoporosis, but many recent studies have already shown that alterations in degree of mineralization can occur due to a large variety of factors. The transmission X-ray microtomography is one of the most popular methods, which provides the spatial distribution of the total absorption coefficient inside the sample. The aim of this study was to investigate the suitability of using microCT as a supplementary tool for the diagnosis of the health status of human bones. Eleven samples were constructed simulating the physiological range of bone mineral density (BMD) found in cortical human bone. The samples represent healthy mixtures of swine compact bone dried at room temperature, powdered and mixed with fat (0 - 100 % by mass). The samples were imaged by a microfocus tube (Fein-Focus) with focal size of about 60 {mu}m ({+-}5%), and a CCD camera (0.143 mm pixel size) coupled with an intensifier tube with fluoroscope screen at the Nuclear Instrumentation Laboratory (COPPE/UFRJ), Brazil. The images were reconstructed and treated with suitable software developed at the Nuclear Instrumentation Laboratory. The mineral content in cortical bone is defined by the volume of dry, fat-free bone per unit bulk volume of the bone. The volumes were calculated from the bone density using the relationship between volume and density. The densities of fat and bone were taken to be 0.95 g.cm{sup -3} and 1.92 g.cm{sup -3} respectively. The correlation of the measured absorption coefficient with the mineral content

  8. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    Directory of Open Access Journals (Sweden)

    Kaličanin Biljana M.

    2007-01-01

    Full Text Available The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was ascertained by determining the calcium and phosphate content, as a basis of the hydroxyapatite structure. The results show that synthetic CP/PLGA nanocomposite alleviate the rehabilitation of weakened alveolar bone. Due to its osteoconductive effect, CP/PLGA can be the material of choice for bone substitution in the future.

  9. Burden of metastatic bone disease from genitourinary malignancies.

    Science.gov (United States)

    Mulders, Peter F; Abrahamsson, Per-Anders; Bukowski, Ronald M

    2010-11-01

    Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life. Current guidelines recommend screening for bone metastases in men with high-risk prostate cancer, but guidance for screening and treatment of bone metastases from genitourinary cancers varies by country and setting. Several bisphosphonates have been evaluated in the advanced genitourinary cancer setting. Zoledronic acid has demonstrated efficacy in significantly reducing the risk of skeletal-related events in patients with bone metastases from a broad range of solid tumors including prostate, renal and bladder cancers, and is recommended for preserving bone health.

  10. Microarchitectural adaptations in aging and osteoarthrotic subchondral bone tissues

    DEFF Research Database (Denmark)

    Ding, Ming

    2010-01-01

    The human skeleton optimizes its microarchitecture by elaborate adaptations to mechanical loading during development and growth. The mechanisms for adaptation involve a multistep process of cellular mechanotransduction stimulating bone modelling, and remodeling resulting in either bone formation...... into the age-related and OA-related subchondral bone adaptations.   Microarchitectural adaptation in human aging cancellous bone The precision of micro-CT measurement is excellent. Accurate 3-D micro-CT image datasets can be generated by applying an appropriate segmentation threshold. A fixed threshold may...... and the constant nature of connectivity suggest an important bone remodeling mechanism that normal aging tibia may adapt trabecular volume orientation. Namely, that the aging trabeculae align preferentially to the primary loading direction to compensate bone loss (III). Age-related changes in trabecular thickness...

  11. An Analysis of Systematic Elemental Changes in Decomposing Bone.

    Science.gov (United States)

    Walden, Steven J; Mulville, Jacqui; Rowlands, Jeffrey P; Evans, Sam L

    2017-03-10

    The aim of this pilot study was to investigate compositional changes in bone during decomposition. Elemental concentrations of barium, calcium, iron, potassium, magnesium, zinc and phosphorus in porcine bone (as an experimental analog for human bone) were analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES). The samples were taken from porcine bone subjected to shallow burial and surface depositions at 28-day intervals for a period of 140 days. Results indicated that ICP-OES elemental profiling has potential to be developed as a forensic test for determining whether a bone sample originates from the early stages of soft tissue putrefaction. Significant changes in iron, sodium and potassium concentrations were found over 140 days. These elements are known to be primarily associated with proteins and/or tissue fluids within the bone. Changes in their respective concentrations may therefore be linked to dehydration over time and in turn may be indicative of time since deposition.

  12. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  13. Targeting bone physiology for the treatment of metastatic prostate cancer.

    Science.gov (United States)

    Autio, Karen A; Morris, Michael J

    2013-03-01

    Metastatic prostate cancer has a unique predilection for bone that can lead to significant clinical sequelae, such as fracture and cord compression. This tropism for bone yields not only clinical challenges, but also opportunities to understand the tumor biology in bone and to develop relevant therapeutic strategies. The process by which tumor cells migrate to bone, remain dormant, and then colonize and expand is based on complex interactions between prostate cancer tumor cells and the host microenvironment. This review will provide an overview of these interactions as well as therapies targeting osseous metastases in castration-resistant prostate cancer.

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

    Science.gov (United States)

    Kavukcuoglu, Nadire Beril

    -/- bones had significantly lower hardness and elastic modulus compared to Fbn2+/+ bones, but the crystallinity was higher. Type-B carbonate substitution decreased significantly in OC-/- and Fbn2-/- bones compared to their wild-type controls. The thesis has provided new insight into how non-collagenous proteins affect the nanomechanics and chemistry of bone tissue. This information will assist in the development of new treatments for osteopenia/osteoporosis.

  15. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  16. Occlusal effects on longitudinal bone alterations of the temporomandibular joint.

    Science.gov (United States)

    Zhang, J; Jiao, K; Zhang, M; Zhou, T; Liu, X-D; Yu, S-B; Lu, L; Jing, L; Yang, T; Zhang, Y; Chen, D; Wang, M-Q

    2013-03-01

    The pathological changes of subchondral bone during osteoarthritis (OA) development in the temporomandibular joint (TMJ) are poorly understood. In the present study, we investigated the longitudinal alterations of subchondral bone using a rat TMJ-OA model developed in our laboratory. Changes in bone mass were examined by micro-CT, and changes in osteoblast and osteoclast activities were analyzed by real-time PCR, immunohistochemistry, and TRAP staining. Subchondral bone loss was detected from 8 weeks after dental occlusion alteration and reached the maximum at 12 weeks, followed by a repair phase until 32 weeks. Although bone mass increased at late stages, poor mechanical structure and lower bone mineral density (BMD) were found in these rats. The numbers of TRAP-positive cells were increased at 12 weeks, while the numbers of osteocalcin-expressing cells were increased at both 12 and 32 weeks. Levels of mRNA expression of TRAP and cathepsin K were increased at 12 weeks, while levels of ALP and osteocalcin were increased at both 12 and 32 weeks. These findings demonstrated that there is an active bone remodeling in subchondral bone in TMJs in response to alteration in occlusion, although new bone was formed with lower BMD and poor mechanical properties.

  17. Reconstruction of bone fenestration on mandiblar by the guided bone regeneration methods with beta-TCP/PLGC membranes.

    Science.gov (United States)

    Koyama, Yoshihisa; Kikuchi, Masanori; Edamura, Kazuya; Nagaoka, Katsuyoshi; Tanaka, Shigeo; Tanaka, Junzo; Takakuda, Kazuo

    2007-03-01

    Guided Bone Regeneration (GBR) is a method for bone tissue regeneration. In this method, membranes are used to cover bone defects and to block the invasion of the surrounding soft tissues. It would provide sufficient time for the osteogenic cells from bone marrow to proliferate and form new bony tissues. In spite of the potential usefulness of this method, no appropriate materials for the GBR membrane have been developed. Here we design the ideal mechanical properties of the GBR membranes and created novel materials, which is the composite of beta-tricalcium phosphate (beta-TCP) and block copolymer of L-lactide, glycolide, and epsilon-caplolactone (PLGC). In the animal experiments with the use of the GBR membranes for large bone defects, we observed significant enhancement in the bone regeneration after 12 weeks implantation and proved the effectiveness of the materials.

  18. Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

    DEFF Research Database (Denmark)

    Leeming, Diana J; Byrjalsen, Inger; Qvist, Per

    2008-01-01

    BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover...... in breast and prostate cancer patients is associated with an increase in cartilage degradation and to test in vitro whether osteoclasts or cathepsin K alone generate CTXII from human bone. METHODS: The study included 132 breast and prostate cancer patient, where presence of bone metastases was graded...... according to the Soloway score. Total bone resorption (CTXItotal) and cartilage degradation (CTXII) were determined. RESULTS: Breast and prostate cancer patients with bone metastases revealed significant increased levels of CTXItotal at Soloway scores 1 and higher compared to patients without bone...

  19. Marked increase in bone formation markers after cinacalcet treatment by mechanisms distinct from hungry bone syndrome in a haemodialysis patient

    Science.gov (United States)

    Goto, Shunsuke; Fujii, Hideki; Matsui, Yutaka; Fukagawa, Masafumi

    2010-01-01

    A 59-year-old female who was on dialysis due to diabetic nephropathy was referred to our hospital for severe hyperparathyroidism refractory to intravenous vitamin D receptor activator treatment. With subsequent cinacalcet hydrochloride treatment, parathyroid hormone (PTH) levels were only slightly suppressed. However, progressive increases were observed in serum alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BAP) levels with mild hypocalcaemia. A bone biopsy, obtained immediately before surgical parathyroidectomy after 3 months of cinacalcet treatment, revealed no disappearance of osteoclasts. These data suggest that cinacalcet hydrochloride treatment may induce a marked promotion of bone formation by mechanisms distinct from hungry bone syndrome that usually develops after parathyroidectomy. PMID:25949410

  20. Comparison between heparin-conjugated fibrin and collagen sponge as bone morphogenetic protein-2 carriers for bone regeneration

    OpenAIRE

    Yang, Hee Seok; La, Wan-Geun; Cho, Yong-Min; Shin, Wangsoo; Yeo, Guw-Dong; Kim, Byung-Soo

    2012-01-01

    Bone morphogenetic protein-2 (BMP-2) is used to promote bone regeneration. However, the bone regeneration ability of BMP-2 relies heavily on the delivery vehicle. Previously, we have developed heparin-conjugated fibrin (HCF), a vehicle for long-term delivery of BMP-2 and demonstrated that long-term delivery of BMP-2 enhanced its osteogenic efficacy as compared to short-term delivery at an equivalent dose. The aim of this study was to compare the bone-forming ability of the BMP-2 delivered by ...

  1. Functional status of bone marrow mesenchymal stem cells from osteoarthritis patients and disease development%骨关节炎患者骨髓间充质干细胞的功能状态与病情进展

    Institute of Scientific and Technical Information of China (English)

    王治洲; 关振鹏; 徐超; 韩亚军; 帖小佳; 郭洪亮; 伊力哈木托合提; 王军锋; 闫斌; 毕晓娟

    2015-01-01

    背景:骨髓间充质干细胞对骨和软骨在细胞水平的发育和再生至关重要,其数量缺失和功能受损被广泛认为是骨关节炎病因之一。目的:探讨骨关节炎患者骨髓间充质干细胞功能状态与病情进展的关系。方法:2013年7月至2014年10月间收集3组病例,每组10例,分别为对照组、轻度骨关节炎患者组、重度骨关节炎患者组。获取3组患者股骨或胫骨骨髓5 mL分离培养骨髓间充质干细胞,培养至3代时采用CCK-8法检测各组患者骨髓间充质干细胞的增殖能力,成软骨诱导14 d后行甲苯胺蓝染色鉴定,Real time PCR法检测对照组诱导后软骨细胞特征基因Aggrecan、Col2A1的表达。结果与结论:骨髓间充质干细胞体外培养后贴壁生长,胞浆含有较大的颗粒,核卵圆形,细胞呈多角形、梭形,有多个大小不一的突起,细胞分裂相多见。对照组增殖能力最强,重度骨关节炎患者组增殖能力最弱,但均在培养1周后进入平台期。成软骨诱导14 d后细胞呈多角形、类圆形改变,紫红色异染颗粒分布于胞浆外围。对照组诱导后软骨细胞特征基因 Aggrecan、Col2A1有高表达趋势。结果表明骨关节炎患者骨髓间充质干细胞功能状态与病情严重程度成负相关,其功能状态影响骨关节炎患者的病情进展。%BACKGROUND:Bone marrow mesenchymal stem cels are crucial for bone and cartilage development and regeneration at a celular level. Insufficient quantity and functional impairment of bone marrow mesenchymal stem cels is widely considered to be one of osteoarthritis causes. OBJECTIVE: To explore the relationship between the functional status of bone marrow mesenchymal stem cels and disease progression in osteoarthritis patients.METHODS: Thirty patients with osteoarthritis were enroled from July 2013 to October 2014, and divided into control, mild osteoarthritis, and severe osteoarthritis

  2. Effects of multi-deficiencies-diet on bone parameters of peripheral bone in ovariectomized mature rat.

    Directory of Open Access Journals (Sweden)

    Thaqif El Khassawna

    Full Text Available Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus. 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8 were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum l