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Sample records for adult human bone

  1. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

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

    2016-01-01

    . Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...... through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP...... family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  4. Increased presence of capillaries next to remodeling sites in adult human cancellous bone

    DEFF Research Database (Denmark)

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

    2013-01-01

    by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic-vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis...

  5. Differentiation of adult human bone marrow mesenchymal stem cells into Schwann-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Li-ye; ZHENG Jia-kun; WANG Chao-yang; LI Wen-yu

    2005-01-01

    Objective: To investigate the differentiative capability of adult human bone marrow mesenchymal stem cells (BMSCs) into Schwann-like cells. Methods: Bone marrows were aspirated from healthy donors and mononuclear cells were separated by Percoll lymphocytes separation liquid (1.073 g/ml) with centrifugation, cells were cultured in DMEM/F12 (1:1) medium containing 10% fetal bovine serum (FBS), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml basic fibroblast growth factor (bFGF). Cells of passage 1 were identified with immunocytochemistry. Conclusions: Bone marrow contains the stem cells with the ability of differentiating into Schwann-like cells, which may represent an alternative stem cell sources for neural transplantation.

  6. Sustained Engraftment of Cryopreserved Human Bone Marrow CD34(+) Cells in Young Adult NSG Mice.

    Science.gov (United States)

    Wiekmeijer, Anna-Sophia; Pike-Overzet, Karin; Brugman, Martijn H; Salvatori, Daniela C F; Egeler, R Maarten; Bredius, Robbert G M; Fibbe, Willem E; Staal, Frank J T

    2014-06-01

    Hematopoietic stem cells (HSCs) are defined by their ability to repopulate the bone marrow of myeloablative conditioned and/or (lethally) irradiated recipients. To study the repopulating potential of human HSCs, murine models have been developed that rely on the use of immunodeficient mice that allow engraftment of human cells. The NSG xenograft model has emerged as the current standard for this purpose allowing for engraftment and study of human T cells. Here, we describe adaptations to the original NSG xenograft model that can be readily implemented. These adaptations encompass use of adult mice instead of newborns and a short ex vivo culture. This protocol results in robust and reproducible high levels of lympho-myeloid engraftment. Immunization of recipient mice with relevant antigen resulted in specific antibody formation, showing that both T cells and B cells were functional. In addition, bone marrow cells from primary recipients exhibited repopulating ability following transplantation into secondary recipients. Similar results were obtained with cryopreserved human bone marrow samples, thus circumventing the need for fresh cells and allowing the use of patient derived bio-bank samples. Our findings have implications for use of this model in fundamental stem cell research, immunological studies in vivo and preclinical evaluations for HSC transplantation, expansion, and genetic modification.

  7. Selection of apoptotic cell specific human antibodies from adult bone marrow.

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    Caroline Grönwall

    Full Text Available Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.

  8. Differences in compact bone tissue microscopic structure between adult humans (Homo sapiens) and Assam macaques (Macaca assamensis).

    Science.gov (United States)

    Nganvongpanit, Korakot; Phatsara, Manussabhorn; Settakorn, Jongkolnee; Mahakkanukrauh, Pasuk

    2015-09-01

    This study investigated the osteon structure of adult humans and Assam macaques, which served as a nonhuman primate model, to find an adequate key for species identification. Samples of compact bone from humans (n=5) and Assam macaques (n=5) - including humerus (n=20), radius (n=20), ulna (n=20), femur (n=20), tibia (n=20) and fibula (n=20) - were processed using conventional histological techniques. 100 secondary osteons from each sample were evaluated under light microscopy. Parameter measurements included: diameter, perimeter and area of Haversian canal and osteon; distance between centers of Haversian canals; and ratio between diameter of Haversian canal and osteon. Four parameters, including diameters and areas of Haversian canal and osteon, demonstrated significantly higher (P<0.05) values in humans than in Assam macaques. Therefore, compact bone microstructure could thus be used as a potential tool to differentiate human and nonhuman primates.

  9. Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells

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    M Mumme

    2012-09-01

    Full Text Available Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1β (IL-1β on the main events of endochondral bone formation by human bone marrow mesenchymal stromal cells (BM-MSC, namely cell proliferation, differentiation and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of IL-1β (50 pg/mL enhanced colony-forming units-fibroblastic (CFU-f and -osteoblastic (CFU-o number (up to 1.5-fold and size (1.2-fold in the absence of further supplements and glycosaminoglycan accumulation (1.4-fold upon BM-MSC chondrogenic induction. In osteogenically cultured BM-MSC, IL-1β enhanced calcium deposition (62.2-fold and BMP-2 mRNA expression by differential activation of NF-κB and ERK signalling. IL-1β-treatment of BM-MSC generated cartilage resulted in higher production of MMP-13 (14.0-fold in vitro, mirrored by an increased accumulation of the cryptic cleaved fragment of aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas, resulting in the formation of mature bone and bone marrow after 12 weeks. In conclusion, IL-1β finely modulates early and late events of the endochondral bone formation by BM-MSC. Controlling the inflammatory environment could enhance the success of therapeutic approaches for the treatment of fractures by resident MSC and as well as improve the engineering of implantable tissues.

  10. Comparison of hematopoietic supportive capacity between human fetal and adult bone marrow mesenchymal stem cells in vitro.

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    Liu, Meng; Yang, Shao-Guang; Xing, Wen; Lu, Shi-Hong; Zhao, Qin-Jun; Ren, Hong-Ying; Chi, Ying; Ma, Feng-Xia; Han, Zhong-Chao

    2011-08-01

    Hematopoietic stem cells (HSC) shift from fetal liver and spleen to bone marrow at neonatal stages and this movement may be due to inductive signals from different microenvironments. Mesenchymal stem cells (MSC) are the precursors of stromal cells in bone marrow microenvironments such as osteoblasts and endothelial cells. Some researchers speculated that fetal bone marrow before birth might be not perfectly suit HSC growth. However, it is still lack of direct evidence to prove this hypothesis. This study was aimed to compare the hematopoietic supportive capacity between human fetal and adult bone marrow MSC in vitro. Adult bone marrow MSC (ABM-MSC) were isolated from three healthy donors and fetal bone marrow MSC (FBM-MSC) were isolated from three fetuses between gestations of 19 to 20 weeks. After irradiation, MSC were co-cultured with CD34(+) cells isolated from umbilical cord blood in long-term culture-initiating cell (LTC-IC) assay. The colony number of colony forming cells (CFC) was counted and the phenotypic changes of co-cultured CD34(+) cells were analyzed by flow cytometry. Cytokine expressions in both kinds of MSC were detected by reverse transcription polymerase chain reaction (RT-PCR). The results showed that ABM-MSC had a stronger hematopoietic supportive capacity than FBM-MSC. Both of them enhanced the differentiation of CD34(+) cells into myeloid lineages. Cytokines were expressed differently in ABM-MSC and FBM-MSC. It is concluded that ABM-MSC possess more potential application in some treatments than FBM-MSC, especially in hematopoietic reconstitution.

  11. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra;

    2014-01-01

    Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...

  12. Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice.

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    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Abou-El-Mahasen, Mona A; Ashamallah, Sylvia A; Khater, Sherry M; El-Halawani, Sawsan M; Ibrahim, Rana Y; Uin, Gan Shu; Kloc, Malgorzata; Calne, Roy Y; Ghoneim, Mohamed A

    2013-01-01

    Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ∼5-10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months

  13. In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells

    LENUS (Irish Health Repository)

    Farrell, Eric

    2011-01-31

    Abstract Background Bone grafts are required to repair large bone defects after tumour resection or large trauma. The availability of patients\\' own bone tissue that can be used for these procedures is limited. Thus far bone tissue engineering has not lead to an implant which could be used as alternative in bone replacement surgery. This is mainly due to problems of vascularisation of the implanted tissues leading to core necrosis and implant failure. Recently it was discovered that embryonic stem cells can form bone via the endochondral pathway, thereby turning in-vitro created cartilage into bone in-vivo. In this study we investigated the potential of human adult mesenchymal stem cells to form bone via the endochondral pathway. Methods MSCs were cultured for 28 days in chondrogenic, osteogenic or control medium prior to implantation. To further optimise this process we induced mineralisation in the chondrogenic constructs before implantation by changing to osteogenic medium during the last 7 days of culture. Results After 8 weeks of subcutaneous implantation in mice, bone and bone marrow formation was observed in 8 of 9 constructs cultured in chondrogenic medium. No bone was observed in any samples cultured in osteogenic medium. Switch to osteogenic medium for 7 days prevented formation of bone in-vivo. Addition of β-glycerophosphate to chondrogenic medium during the last 7 days in culture induced mineralisation of the matrix and still enabled formation of bone and marrow in both human and rat MSC cultures. To determine whether bone was formed by the host or by the implanted tissue we used an immunocompetent transgenic rat model. Thereby we found that osteoblasts in the bone were almost entirely of host origin but the osteocytes are of both host and donor origin. Conclusions The preliminary data presented in this manuscript demonstrates that chondrogenic priming of MSCs leads to bone formation in vivo using both human and rat cells. Furthermore, addition of

  14. Comparison of the neural differentiation potential of human mesenchymal stem cells from amniotic fluid and adult bone marrow.

    Science.gov (United States)

    Yan, Zhong-Jie; Hu, Yu-Qin; Zhang, Hong-Tian; Zhang, Peng; Xiao, Zong-Yu; Sun, Xin-Lin; Cai, Ying-Qian; Hu, Chang-Chen; Xu, Ru-Xiang

    2013-05-01

    Human mesenchymal stem cells (MSCs) are considered a promising tool for cell-based therapies of nervous system diseases. Bone marrow (BM) has been the traditional source of MSCs (BM-MSCs). However, there are some limitations for their clinical use, such as the decline in cell number and differentiation potential with age. Recently, amniotic fluid (AF)-derived MSCs (AF-MSCs) have been shown to express embryonic and adult stem cell markers, and can differentiate into cells of all three germ layers. In this study, we isolated AF-MSCs from second-trimester AF by limiting dilution and compared their proliferative capacity, multipotency, neural differentiation ability, and secretion of neurotrophins to those of BM-MSCs. AF-MSCs showed a higher proliferative capacity and more rapidly formed and expanded neurospheres compared to those of BM-MSCs. Both immunocytochemical and quantitative real-time PCR analyses demonstrated that AF-MSCs showed higher expression of neural stemness markers than those of BM-MSCs following neural stem cell (NSC) differentiation. Furthermore, the levels of brain-derived growth factor and nerve growth factor secreted by AF-MSCs in the culture medium were higher than those of BM-MSCs. In addition, AF-MSCs maintained a normal karyotype in long-term cultures after NSC differentiation and were not tumorigenic in vivo. Our findings suggest that AF-MSCs are a promising and safe alternative to BM-MSCs for therapy of nervous system diseases.

  15. Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

    Science.gov (United States)

    He, Xiaoli; H'ng, Shiau-Chen; Leong, David T; Hutmacher, Dietmar W; Melendez, Alirio J

    2010-08-01

    High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

  16. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs.

    Directory of Open Access Journals (Sweden)

    Federica Collino

    Full Text Available BACKGROUND: Cell-derived microvesicles (MVs have been described as a new mechanism of cell-to-cell communication. MVs after internalization within target cells may deliver genetic information. Human bone marrow derived mesenchymal stem cells (MSCs and liver resident stem cells (HLSCs were shown to release MVs shuttling functional mRNAs. The aim of the present study was to evaluate whether MVs derived from MSCs and HLSCs contained selected micro-RNAs (miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: MVs were isolated from MSCs and HLSCs. The presence in MVs of selected ribonucleoproteins involved in the traffic and stabilization of RNA was evaluated. We observed that MVs contained TIA, TIAR and HuR multifunctional proteins expressed in nuclei and stress granules, Stau1 and 2 implicated in the transport and stability of mRNA and Ago2 involved in miRNA transport and processing. RNA extracted from MVs and cells of origin was profiled for 365 known human mature miRNAs by real time PCR. Hierarchical clustering and similarity analysis of miRNAs showed 41 co-expressed miRNAs in MVs and cells. Some miRNAs were accumulated within MVs and absent in the cells after MV release; others were retained within the cells and not secreted in MVs. Gene ontology analysis of predicted and validated targets showed that the high expressed miRNAs in cells and MVs could be involved in multi-organ development, cell survival and differentiation. Few selected miRNAs shuttled by MVs were also associated with the immune system regulation. The highly expressed miRNAs in MVs were transferred to target cells after MV incorporation. CONCLUSIONS: This study demonstrated that MVs contained ribonucleoproteins involved in the intracellular traffic of RNA and selected pattern of miRNAs, suggesting a dynamic regulation of RNA compartmentalization in MVs. The observation that MV-highly expressed miRNAs were transferred to target cells, rises the possibility that the biological effect of stem

  17. Long-term three-dimensional perfusion culture of human adult bone marrow mononuclear cells in bioreactors.

    Science.gov (United States)

    Schmelzer, Eva; Finoli, Anthony; Nettleship, Ian; Gerlach, Jörg C

    2015-04-01

    The construction and long-term maintenance of three-dimensional in vitro bone marrow models is of great interest but still quite challenging. Here we describe the use of a multi-compartment hollow-fiber membrane based three-dimensional perfusion bioreactor for long-term culture of whole human bone marrow mononuclear cells. We also investigated bioreactors with incorporated open-porous foamed hydroxyapatite scaffolds, mimicking the in vivo bone matrix. Cells in bioreactors with and without scaffolds were cultured to 6 weeks and compared to Petri dish controls. Cells were analyzed for gene expression, surface markers by flow cytometry, metabolic activity, hematopoietic potential, viability, and attachment by immunocytochemistry. Cells in bioreactors were metabolic active during long-term culture. The percentages of hematopoietic stem cell and mature endothelial cell fractions were maintained in bioreactors. The expression of most of the analyzed genes stabilized and increased after long-term culture of 6 weeks. Compared to Petri dish culture controls, bioreactor perfusion culture improved in both the short and long-term, the colony formation unit capacity of hematopoietic progenitors. Cells attached to the ample surface area provided by hydroxyapatite scaffolds. The implementation of a hydroxyapatite scaffold did not influence colony formation capacity, percentages of cell type specific fractions, gene expression, cell viability or metabolic turnover when compared to control cells cultured in bioreactors without scaffolds. In conclusion, three-dimensional perfusion bioreactor culture enables long-term maintenance of primary human bone marrow cells, with hydroxyapatite scaffolds providing an in vivo-like scaffold for three-dimensional culture.

  18. Establishment of human-rhesus chimeric liver using adult bone marrow mesenchymal stem cells%应用成人骨髓间充质干细胞建立人-猴肝脏嵌合体

    Institute of Scientific and Technical Information of China (English)

    何保丽; 马丽花; 陈丽玲; 刘汝文; 杨仁华

    2013-01-01

    BACKGROUND:Human-mammal chimeric liver chimera has been a vital significance for the proliferation and differentiation of bone marrow mesenchymal stem cells. OBJECTIVE:To establish an animal model of human-rhesus chimeric liver using adult bone marrow mesenchymal stem cells. METHODS:Adult bone marrow mesenchymal stem cells were isolated, purified and cultured for the sixth generation. The number of bone marrow mesenchymal stem cells was no less than 5×108. Bone marrow mesenchymal stem cells labeled with green fluorescent protein were transplanted into the liver of the embryo rhesus with pregnancy of 10 weeks under guided by type-B ultrasound. At the 1st and 3rd months of birth, the liver tissue of the infant rhesus was taken for biopsy. After routine pathological section, histological specimens were observed under fluorescence microscope to confirm if there were adult bone marrow mesenchymal stem cells positive for green fluorescent protein and their distribution, and detected by immunohistochemical staining to identify if human albumin expressed in the liver of infant rhesus. RESULTS AND CONCLUSION:Fluorescence microscope observation indicated that at the 1st and 3rd months after birth, there were surviving bone marrow mesenchymal stem cells derived from human with green fluorescence in the liver of infant rhesus, and these cells migrated to form more concentrated distribution. The immunohistochemical results demonstrated that functional liver cells expressing human albumin were observed in the liver of infant rhesus at the 1st and 3rd months after birth, and their distribution was in accordance with bone marrow mesenchymal stem cells with green fluorescence. Human-rhesus chimeric liver can be established using adult bone marrow mesenchymal stem cells, which can generate functional liver cells in the liver of infant rhesus.%BACKGROUND:Human-mammal chimeric liver chimera has been a vital significance for the proliferation and differentiation of bone marrow

  19. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. Human bone marrow-derived adult stem cells for post-myocardial infarction cardiac repair: current status and future directions.

    Science.gov (United States)

    Wei, H M; Wong, P; Hsu, L F; Shim, W

    2009-10-01

    Stem cell-based cell therapy has emerged as a potentially therapeutic option for patients with acute myocardial infarction (AMI) and heart failure. With the completion of a number of trials using bone marrow (BM)-derived adult stem cells, critical examination of the overall clinical benefits, limitations and potential side effects of this revolutionary treatment will pave the way for future clinical research. At present, clinical trials have been conducted almost exclusively using BM stem cells. The primary endpoints of these trials are mainly safety and feasibility, with secondary endpoints in the efficacy of post-myocardial infarction (MI) cardiac repair. Intervention with BM-derived cells was mainly carried out by endogenously-mobilised BM cells with granulocyte-colony stimulating factor, and more frequently, by intracoronary infusion or direct intramyocardial injection of autologous BM cells. While these studies have been proven safe and feasible without notable side effects, mixed outcomes in terms of clinical benefits have been reported. The major clinical benefits observed are improved cardiac contractile function and suppressed left ventricular negative remodelling, including reduced infarct size and improved cardiac perfusion of infarct zone. Moderate and transient clinical benefits have been mostly observed in studies with intracoronary infusion or direct intramyocardial injection of BM cells. These effects are widely considered to be indirect effects of implanted cells in association with paracrine factors, cell fusion, passive ventricular remodelling, or the responses of endogenous cardiac stem cells. In contrast, evidence of cardiac regeneration characterised by differentiation of implanted stem cells into cardiomyocytes and other cardiac cell lineages, is weak or lacking. To elucidate a clear risk-benefit of this exciting therapy, future studies on the mechanisms of cardiac cell therapy will need to focus on confirming the ideal cell types in relation

  1. Mesangiogenic Progenitor Cells Derived from One Novel CD64brightCD31brightCD14neg Population in Human Adult Bone Marrow

    Science.gov (United States)

    Barachini, Serena; Montali, Marina; Carnicelli, Vittoria; Fazzi, Rita; Parchi, Paolo; Petrini, Mario

    2016-01-01

    Mesenchymal stromal cells (MSCs) have been the object of extensive research for decades, due to their intrinsic clinical value. Nonetheless, the unambiguous identification of a unique in vivo MSC progenitor is still lacking, and the hypothesis that these multipotent cells could possibly arise from different in vivo precursors has been gaining consensus in the last years. We identified a novel multipotent cell population in human adult bone marrow that we first named Mesodermal Progenitor Cells (MPCs) for the ability to differentiate toward the mesenchymal lineage, while still retaining angiogenic potential. Despite extensive characterization, MPCs positioning within the differentiation pathway and whether they can be ascribed as possible distinctive progenitor of the MSC lineage is still unclear. In this study, we describe the ex vivo isolation of one novel bone marrow subpopulation (Pop#8) with the ability to generate MPCs. Multicolor flow cytometry in combination with either fluorescence-activated cell sorting or magnetic-activated cell sorting were applied to characterize Pop#8 as CD64brightCD31brightCD14neg. We defined Pop#8 properties in culture, including the potential of Pop#8-derived MPCs to differentiate into MSCs. Gene expression data were suggestive of Pop#8 in vivo involvement in hematopoietic stem cell niche constitution/maintenance. Pop#8 resulted over three logs more frequent than other putative MSC progenitors, corroborating the idea that most of the controversies regarding culture-expanded MSCs could be the consequence of different culture conditions that select or promote particular subpopulations of precursors. PMID:26975798

  2. Co-transplantation of human fetal thymus, bone and CD34(+) cells into young adult immunodeficient NOD/SCID IL2Rγ(null) mice optimizes humanized mice that mount adaptive antibody responses.

    Science.gov (United States)

    Chung, Yun Shin; Son, Jin Kyung; Choi, Bongkum; Joo, Sung-Yeon; Lee, Yong-Soo; Park, Jae Berm; Moon, Hana; Kim, Tae Jin; Kim, Se Ho; Hong, Seokmann; Chang, Jun; Kang, Myung-Soo; Kim, Sung Joo

    2015-04-01

    Both the thymus (T) and bone (B) are necessary hematopoietic niches in adult humans. We previously showed that co-transplantation of human fetal T and B tissues into neonatal immunodeficient NOD/SCID IL2Rγ(null) (NSG, N) mice facilitated hematopoiesis. However, transplantation into neonatal mice resulted in high frequency of early death, making it unrealistic for repetitive experiments. In this study, young adult N mice were pre-engrafted with T and B, T alone, B alone or no tissues. The animals were irradiated and injected with autologous fetal liver (FL)-derived CD34(+) cells (34). The resultant mice were TB34N, T34N, B34N and 34N, respectively, and challenged with T cell dependent antigens (Ags). The humanized TB34N mice showed best performance of these mouse models in many aspects resembling the adult human Ag-experienced spleen. The TB34N mice exhibited better hematopoietic reconstitution; balanced development of T- and B-cell, and common progenitor cells; follicular lymphoid structures with a functional germinal center (GC) enriched with follicular dendritic cells (FDCs) and plasma cells (PCs); secretion of hIgG in the sera in response to Ags at comparable levels to those of human; derivations of hIgG mAb-secreting hybridoma clones. Collectively, the humanized TB34N mice could develop an adaptive immunity that was capable of producing Ag-specific hIgG at a significant level via class switching. This unprecedented TB34N platform in humanized mice would be useful in dissecting human immunity, for generating human Abs and clinical applications.

  3. Morphological Study of Wormian Bones in Dried Human Skulls

    OpenAIRE

    Divyesh Patel; Ketan Chauhan; Dhananjay Patil

    2015-01-01

    Background: Wormian bones may be defined as a those accidental bones found in the cranium having no regular relation to their normal ossification centre. They are assocated with cranial and central nervous system abnormalities. Knowledge of these bones is important for anthropo-logists, forensic experts, radiologists, orthopedic and neurosurgeons to avoid misleading for multiple fractures of the skull. Materials and Methods: Adult dry human skulls (n= 27) of unknown age and sex availablei...

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

    Directory of Open Access Journals (Sweden)

    Vinken Mathieu

    2007-04-01

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

  5. The effect of ceramic bovine bone on growth and differentiation of adult human bone marrow stromal cells%陶瓷化骨对成人骨髓基质干细胞分化的影响

    Institute of Scientific and Technical Information of China (English)

    谭勇海; 姜苗苗; 韩海霞; 于海勇

    2012-01-01

    目的:观察陶瓷化骨时成人骨髓基质干细胞生长和分化的影响.方法:体外分离培养成人骨髓基质干细胞,将第二代细胞以陶瓷化骨为载体进行培养,利用倒置显微镜、碱性磷酸酶细胞化学染色、碱性磷酸酶活性检测等条件,了解陶瓷化骨对成人骨髓基质干细胞生物学行为的影响.结果:体外连续培养6d,倒置显微镜下可见成人骨髓基质干细胞与陶瓷化骨相容性好,材料周边细胞生长密集,并有向陶瓷化骨趋化迁移现象,3周后形成矿化结节.碱性磷酸酶染色呈阳性、碱性磷酸酶活性检测有明显的细胞分泌量.结论:体外培养条件下,陶瓷化骨可诱导成人骨髓基质干细胞向成骨和骨质细胞分化.%To observe the effect of ceramic bovine bone(CBB) on growth and differentiation of adult human bone marrow stromal cells(hBMSCs) in vitro. Methods:The hBMSCs were cultured in vitro,the second generation of cells were cultured with CBB as the carrier,inverted microscope,alkaline phosphatase( AKP) staining, ALP activity detection conditions were used to investigate effect of CBB on hBMSCs biological behavior. Results:After continuous cultivation in vitro for 6 Days, hBMSCs and CBB showed good compatibility under inverted microscope,the cells were densely distributed around the material and showed CBB chemotactic migration, the formation of mineralized nodules. AKP staining showed positive and significant secretion was detected. Conclusion: CBB could induced hBMSCs to differentiated into osteoblasts and bone cells in vitro conditions.

  6. 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.)

  7. Electron absorbed fractions of energy and S-values in an adult human skeleton based on {mu}CT images of trabecular bone

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, R; Cassola, V F; Khoury, H J; De O Lira, C A B [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Professor Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Richardson, R B [Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, ON, K0J 1J0 (Canada); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); Brown, K Robson, E-mail: rkramer@uol.com.br [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)

    2011-03-21

    When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on {mu}CT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 {mu}m thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters {sup 14}C, {sup 59}Fe, {sup 131}I, {sup 89}Sr, {sup 32}P and {sup 90}Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 {mu}m endosteum and the previously recommended 10 {mu}m endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by {approx}20% when the beta emitters are in marrow.

  8. Bone dosimetry using synthetic images to represent trabecular bones of five regions of the human body

    Energy Technology Data Exchange (ETDEWEB)

    Lima Filho, Jose de M. [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFPE), Recife, PE (Brazil); Vieira, Jose W. [Escola Politecnica de Pernambuco (POLI). Universidade de Pernambuco (UPE), Recife, PE (Brazil); Lima, Vanildo J. de M., E-mail: vjr@ufpe.br [Departamento de Anatomia. Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Lima, Lindeval F., E-mail: lindeval@dmat.ufrr.br [Departamento de Matematica (DMAT). Universidade Federal de Roraima (UFRR), Boa Vista, RR (Brazil); Lima, Fernando R.A., E-mail: falima@cnen.gov.br [Centro Regional de Ciencias Nucleares (CRCN/NE-CNEN-PE), Recife, PE (Brazil); Vasconcelos, Wagner E. de [Departamento de Energia Nuclear (DEN). Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

    2011-07-01

    One of the greatest challenges in numerical dosimetry of ionizing radiation is to estimate the absorbed dose by bone tissue in the human body. The bone tissues of greater radiosensitivity are the red bone marrow (RBM), that consist of the hematopoietic cells, located within the trabecular bones, and the bone surface cells (BSC), called osteogenic cells. The report 70 of the ICRP lists five spongiosa regions with their respective volume percent of trabecular bone: ribs (also contemplating the clavicles and sternum), spine, long bones, pelvis and skull (also contemplating mandible). The Grupo de Pesquisa em Dosimetria Numerica (GDN/CNPq) has been built exposure computational models (ECMs) based on voxel phantoms and EGSnrc Monte Carlo code. To estimate the energy deposited in the RBM and in the BSC of a phantom, the GDN/CNPq has used a method based on micro-CT images of the five trabecular regions mentioned above. These images were provided by other research institutes and were obtained from scan of bone samples of adult. Here is the greatest difficulty in reproducing this method: besides the need for bone images of real people with micrometer resolution, the distribution of bone marrow in the human body, according to ICRP 70, varies with age. This article presents some proposals of the GDN/CNPQ for replacing in the ECMs the micro-CT images by images synthesized by the computer, based on Monte Carlo sampling. (author)

  9. RNA-Seq Reveals the Angiogenesis Diversity between the Fetal and Adults Bone Mesenchyme Stem Cell.

    Science.gov (United States)

    Zhao, Xin; Han, Yingmin; Liang, Yu; Nie, Chao; Wang, Jian

    2016-01-01

    In this research, we used RNA sequencing (RNA-seq) to analyze 23 single cell samples and 2 bulk cells sample from human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. The results from the research demonstrated that there were big differences between two cell lines. Adult bone mesenchyme stem cell lines showed a strong trend on the blood vessel differentiation and cell motion, 48/49 vascular related differential expressed genes showed higher expression in adult bone mesenchyme stem cell lines (Abmsc) than fetal bone mesenchyme stem cell lines (Fbmsc). 96/106 cell motion related genes showed the same tendency. Further analysis showed that genes like ANGPT1, VEGFA, FGF2, PDGFB and PDGFRA showed higher expression in Abmsc. This work showed cell heterogeneity between human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. Also the work may give an indication that Abmsc had a better potency than Fbmsc in the future vascular related application.

  10. Infant milk feeding influences adult bone health: a prospective study from birth to 32 years.

    Directory of Open Access Journals (Sweden)

    Satu Pirilä

    Full Text Available BACKGROUND: Peak bone mass, attained by early adulthood, is influenced by genetic and life-style factors. Early infant feeding and duration of breastfeeding in particular, associate with several health-related parameters in childhood. The aim of this study was to examine whether the effects of early infant feeding extend to peak bone mass and other bone health characteristics at adult age. METHODS AND FINDINGS: A cohort of 158 adults (76 males born in Helsinki, Finland, 1975, prospectively followed up from birth, underwent physical examination and bone densitometry to study bone area, bone mineral content (BMC, and bone mineral density (BMD at 32 years of age. Life-style factors relevant for bone health were recorded. For data analysis the cohort was divided into three equal-size groups according to the total duration of breastfeeding (BF: Short (≤3 months, Intermediate and Prolonged (≥7 months BF groups. In males short BF is associated with higher bone area, BMC, and BMD compared to longer BF. Males in the Short BF group had on average 4.7% higher whole body BMD than males in the Prolonged BF group. In multivariate analysis, after controlling for multiple confounding factors, the influence of BF duration on adult bone characteristics persisted in males. Differences between the three feeding groups were observed in lumbar spine bone area and BMC, and whole body BMD (MANCOVA; p = 0.025, p = 0.013, and p = 0.048, respectively, favoring the Short BF group. In women no differences were observed. CONCLUSIONS: In men, early infant milk feeding may have a significant impact on adult bone health. A potential explanation is that the calcium and phosphate contents were strikingly higher in formula milk and commercial cow milk/cow milk dilutions as opposed to human milk. Our novel finding merits further studies to determine means to ensure optimal bone mass development in infants with prolonged breastfeeding.

  11. Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

    Science.gov (United States)

    Croker, Sarah L; Reed, Warren; Donlon, Denise

    2016-03-01

    The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone

  12. 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.

  13. Atomic scale chemical tomography of human bone

    Science.gov (United States)

    Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

    2017-01-01

    Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale – the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

  14. Morphological Study of Wormian Bones in Dried Human Skulls

    Directory of Open Access Journals (Sweden)

    Divyesh Patel

    2015-09-01

    Full Text Available Background: Wormian bones may be defined as a those accidental bones found in the cranium having no regular relation to their normal ossification centre. They are assocated with cranial and central nervous system abnormalities. Knowledge of these bones is important for anthropo-logists, forensic experts, radiologists, orthopedic and neurosurgeons to avoid misleading for multiple fractures of the skull. Materials and Methods: Adult dry human skulls (n= 27 of unknown age and sex availablein the Department of Anatomy, Govt. Medical College, Surat were included in the study. Result: Overall incidence of wormian bone was 44.4%. They occurred more frequently at lambdoid suture (48.14%.Wormian bones were also presentat asterion (18.5%, along the coronal suture (0.03%, along the parito-temporal suture (0.07%, along the occipito-mastoid suture (0.03%,andat pterion (0.03 %. Wormain bones were found 48.1% on left half of skull and 37.03% on right half of skull. Conclusion: The Wormian bones were more frequent at the lambdoid suture. The clinical importances of these variant bones were emphasized with relevant review of literature. [Natl J Med Res 2015; 5(3.000: 222-225

  15. 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...

  16. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

  17. Distribution and viability of fetal and adult human bone marrow stromal cells in a biaxial rotating vessel bioreactor after seeding on polymeric 3D additive manufactured scaffolds

    Directory of Open Access Journals (Sweden)

    Anne eLeferink

    2015-10-01

    Full Text Available One of the conventional approaches in tissue engineering is the use of scaffolds in combination with cells to obtain mechanically stable tissue constructs in vitro prior to implantation. Additive manufacturing by fused deposition modeling is a widely used technique to produce porous scaffolds with defined pore network, geometry, and therewith defined mechanical properties. Bone marrow derived mesenchymal stromal cells (MSCs are promising candidates for tissue engineering based cell therapies due to their multipotent character. One of the hurdles to overcome when combining additive manufactured scaffolds with MSCs is the resulting heterogeneous cell distribution and limited cell proliferation capacity. In this study, we show that the use of a biaxial rotating bioreactor, after static culture of human fetal MSCs (hfMSCs seeded on synthetic polymeric scaffolds, improved the homogeneity of cell and extracellular matrix (ECM distribution and increased the total cell number. Furthermore, we show that the relative mRNA expression levels of indicators for stemness and differentiation are not significantly changed upon this bioreactor culture, whereas static culture shows variations of several indicators for stemness and differentiation. The biaxial rotating bioreactor presented here offers a homogeneous distribution of hfMSCs, enabling studies on MSCs fate in additive manufactured scaffolds without inducing undesired differentiation.

  18. Distribution and Viability of Fetal and Adult Human Bone Marrow Stromal Cells in a Biaxial Rotating Vessel Bioreactor after Seeding on Polymeric 3D Additive Manufactured Scaffolds.

    Science.gov (United States)

    Leferink, Anne M; Chng, Yhee-Cheng; van Blitterswijk, Clemens A; Moroni, Lorenzo

    2015-01-01

    One of the conventional approaches in tissue engineering is the use of scaffolds in combination with cells to obtain mechanically stable tissue constructs in vitro prior to implantation. Additive manufacturing by fused deposition modeling is a widely used technique to produce porous scaffolds with defined pore network, geometry, and therewith defined mechanical properties. Bone marrow-derived mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering-based cell therapies due to their multipotent character. One of the hurdles to overcome when combining additive manufactured scaffolds with MSCs is the resulting heterogeneous cell distribution and limited cell proliferation capacity. In this study, we show that the use of a biaxial rotating bioreactor, after static culture of human fetal MSCs (hfMSCs) seeded on synthetic polymeric scaffolds, improved the homogeneity of cell and extracellular matrix distribution and increased the total cell number. Furthermore, we show that the relative mRNA expression levels of indicators for stemness and differentiation are not significantly changed upon this bioreactor culture, whereas static culture shows variations of several indicators for stemness and differentiation. The biaxial rotating bioreactor presented here offers a homogeneous distribution of hfMSCs, enabling studies on MSCs fate in additive manufactured scaffolds without inducing undesired differentiation.

  19. Risk factors for low bone mass in healthy young adults from North India: studies on BMD and bone turnover markers

    Directory of Open Access Journals (Sweden)

    Anita Fotedar Verma

    2015-04-01

    Full Text Available Background: Despite availability of adequate sunshine, Indian population has the highest prevalence of low bone mass and Bone Mineral Content (BMC. Risk factors for osteoporosis have been extensively studied in the west but poorly investigated in India. We studied BMD and Bone Turnover Markers (BTMs among healthy young adults. Methods: Fifty one healthy young adults (28 Males, 23 Females in the age group of 20-35 years were studied. Morphometric, biochemical parameters and BMD (whole body, spine, hip and wrist were recorded. Anthropometric measurements included height, weight, BMI and Waist/Hip Ratio (WHR. BTMs studied included - serum Bone-Specific Alkaline Phosphatase (sBAP, serum Collagen cross-linked C-Terminal telopeptide (sCTx, serum Osteocalcin (OC and human intact parathyroid hormone (hPTH using standard ELISA kits. Results: Of 51 healthy volunteers 21.57% had normal BMD, 13.73% were frankly osteoporotic and 64.70% were osteopenic. Age, weight and BMI were the best predictors of total BMD and BMC at all sites. sCTX positively correlated with Total Bone Area (TBA, BMD at Hip and Forearm. Using multiple regressions - age, weight, and BMI were significant predictors of BMD in young adults. Percentage body fat had inverse correlation with BMC, BMD and TBA. Weight and height positively correlated with BMD at femoral neck, inter-trochanter and Ward's triangle. Body weight was best predictor of BMD at femoral neck, Ward's triangle, forearm UD, forearm MID and forearm1/3. Conclusion: Majority of healthy young Indians have poor bone health as evidenced by bone markers. [Int J Res Med Sci 2015; 3(4.000: 933-939

  20. Recent advances in bone regeneration using adult stemcells

    Institute of Scientific and Technical Information of China (English)

    Hadar Zigdon-Giladi; Utai Rudich; Gal Michaeli Geller; Ayelet Evron

    2015-01-01

    Bone is a highly vascularized tissue reliant on theclose spatial and temporal association between bloodvessels and bone cells. Therefore, cells that participatein vasculogenesis and osteogenesis play a pivotalrole in bone formation during prenatal and postnatalperiods. Nevertheless, spontaneous healing of bonefracture is occasionally impaired due to insufficientblood and cellular supply to the site of injury. In thesecases, bone regeneration process is interrupted, whichmight result in delayed union or even nonunion ofthe fracture. Nonunion fracture is difficult to treatand have a high financial impact. In the last decade,numerous technological advancements in bone tissueengineering and cell-therapy opened new horizon inthe field of bone regeneration. This review starts withpresentation of the biological processes involved inbone development, bone remodeling, fracture healingprocess and the microenvironment at bone healingsites. Then, we discuss the rationale for using adultstem cells and listed the characteristics of the availablecells for bone regeneration. The mechanism of actionand epigenetic regulations for osteogenic differentiationare also described. Finally, we review the literature fortranslational and clinical trials that investigated the useof adult stem cells (mesenchymal stem cells, endothelialprogenitor cells and CD34+ blood progenitors) for boneregeneration.

  1. Bone blood flow and metabolism in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Kemppainen, Jukka; Kaskinoro, Kimmo;

    2012-01-01

    Human bone blood flow and metabolism during physical exercise remains poorly characterised. In the present study we measured femoral bone blood flow and glucose uptake in young healthy subjects by positron emission tomography in three separate protocols. In six women, blood flow was measured...... in femoral bone at rest and during one leg intermittent isometric exercise with increasing exercise intensities. In nine men, blood flow in femur was determined at rest and during dynamic one leg exercise, and two other physiological perturbations: moderate systemic hypoxia (14 O(2) ) at rest and during...... exercise, and during intra-femoral infusion of high-dose adenosine. Bone glucose uptake was measured at rest and during dynamic one leg exercise in five men. The results indicate that isometric exercise increased femoral bone blood flow from rest (1.8 ± 0.6 ml/100g/min) to low intensity exercise (4.1 ± 1...

  2. Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

    Directory of Open Access Journals (Sweden)

    N. K. Venkataramana

    2012-01-01

    Full Text Available The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during “on” and 31.21% during “off” period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years showed more improvement and no further disease progression than the later stages (11–15 years. However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

  3. Bone and mineral metabolism in adult celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  4. Age changes in human bone: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, W.D.

    1977-12-03

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

  5. 珊瑚羟基磷灰石与成人骨髓源成骨细胞的相容性研究%Biocompatibility of coral hydroxyapatite and adult human osteoblasts derived from bone marrow

    Institute of Scientific and Technical Information of China (English)

    任高宏; 刘晓静; 裴国献

    2004-01-01

    artificially cannot satisfy the clinical requirements for a variety of malpractices. The establishment and fast development of tissue engineering bring new hope for the repair of bone defect. This technology gets rid of the former mode and has brought broad prospect for made the traditional bone transplantation by composition in vitro and recombination in vivo.OBJECTIVE: To study the biocompatibility of coral hydroxyapatite(CHA)and adult human osteoblasts derived from bone marrow and cultured in vitro in order to explore for appropriate scaffold materials for bone tissue engineering.DESIGN: A randomly and controlled experimental study was corducted.SETTING, METERIALS and INTERVENTION: The experiment was finished in the Laboratory of Tissue Engineering, Department of Orthopedics Center, Nanfang Hospital, First Military Medical University. Bone marrow was aspirated from the healthy adult human volunteer and cultured in high-glucose Dulbecco's modified Eagle's medium ( DMEM ) containing 100 g/L fetal bovine serum. Subsequently, dexamethasone, beta-sodium glycerophosphate and ascorbic acid were added into the culture mediumfor subculture. Their passages were divided into two groups, osteoblasts cultured together with CHA as the experimental group: and osteoblasts cultured without CHA as the control group. Morphologies of all these cultured cells in the two groups were observed continually under an inverted phase contrast microscope, a light microscope with HE stained, and a scanning electron microscope. Growth of the cultured osteoblasts in the two groups were evaluated by MTT. Content of proteins was assayed by Coomassie Brilliant Blue G250,and activities of alkaline phosphatase(ALP) were quantitatively detected by ALP test kit at each different point of time.MAIN OUTCOME MEASURES: Observation of the growth condition of compound or imcompound CHA osteoblast when the adult human osteoblast is cultured in vitro, and the test result of cell function of the compound cultured cells

  6. Bone mineral density in adult coeliac disease: An updated review

    Directory of Open Access Journals (Sweden)

    Alfredo J. Lucendo

    2013-03-01

    Full Text Available Introduction and objectives: coeliac disease (CD affects around 1-2 % of the world population. Most patients are now diagnosed when adults, suffering the consequences of an impaired bone mineralization. This review aims to provide an updated discussion on the relationship between low bone mineral density (BMD, osteopenia and osteoporosis, and CD. Methods: a PubMed search restricted to the last 15 years was conducted. Sources cited in the results were also reviewed to identify potential sources of information. Results: low BMD affects up to 75 % of celiac patients, and can be found at any age, independently of positive serological markers and presence of digestive symptoms. The prevalence of CD among osteoporotic patients is also significantly increased. Two theories try to explain this origin of low BMD: Micronutrients malabsorption (including calcium and vitamin D determined by villous atrophy has been related to secondary hyperparathyroidism and incapacity to achieve the potential bone mass peak; chronic inflammation was also related with RANKL secretion, osteoclasts activation and increased bone resorption. As a consequence, celiac patients have a risk for bone fractures that exceed 40 % that of matched non-affected population. Treatment of low BMD in CD comprises gluten-free diet, calcium and vitamin D supplementation, and biphosphonates, although its effects on CD have not been specifically assessed. Conclusions: up to 75 % of celiac patients and 40 % of that diagnosed in adulthood present a low BMD and a variable increase in the risk of bone fractures. Epidemiological changes in CD make bone density scans more relevant for adult coeliacs.

  7. Optimal therapy for adults with Langerhans cell histiocytosis bone lesions.

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    Maria A Cantu

    Full Text Available BACKGROUND: There is little data on treatment of Langerhans cell histiocytosis (LCH in adults. Available data is on small numbers of patients with short follow-up times and no comparison of results from different treatment regimens. We analyzed the responses of adult LCH patients with bone lesions to three primary chemotherapy treatments to define the optimal one. METHODS AND FINDINGS: Fifty-eight adult patients with bone lesions, either as a solitary site or as a component of multisystem disease, were analyzed for disease location and response to surgery, curettage, steroids, radiation, vinblastine/prednisone, 2-Chlorodeoxyadenosine (2-CdA, or cytosine arabinoside (ARA-C. The mean age of patients was 32 years, with equal gender distribution. Twenty-nine patients had 1 lesion; 16, 2 lesions; 5, 3 lesions; and 8 had 4 or more. Most bone lesions were in the skull, spine, or jaw. Chemotherapy, surgery, curettage, or radiation, but not steroids alone, achieved improvement or resolution of lesions in a majority of patients. Comparison of the three chemotherapy regimens revealed 84% of patients treated with vinblastine/prednisone either did not respond or relapsed within a year, whereas 59% of patients treated with 2-CdA and 21% treated with ARA-C failed. Toxicity was worse with the vinblastine/prednisone group as 75% had grade 3-4 neuropathy. Grade 3-4 cytopenias occurred in 37% of the 2-CdA -treated patients and 20% of the ARA-C-treated patients. The major limitation of this study is it is retrospective and not a clinical trial. CONCLUSIONS: ARA-C is an effective and minimally toxic treatment for LCH bone lesions in adults. In contrast, vinblastine/prednisone results in poor overall responses and excessive toxicity.

  8. The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth.

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    Yvette M Coulson-Thomas

    Full Text Available Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs. Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS and hyaluronic acid (HA. In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology.

  9. The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth.

    Science.gov (United States)

    Coulson-Thomas, Yvette M; Coulson-Thomas, Vivien J; Norton, Andrew L; Gesteira, Tarsis F; Cavalheiro, Renan P; Meneghetti, Maria Cecília Z; Martins, João R; Dixon, Ronald A; Nader, Helena B

    2015-01-01

    Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology.

  10. Diagnostic dry bone histology in human paleopathology.

    Science.gov (United States)

    de Boer, H H Hans; Van der Merwe, A E Lida

    2016-10-01

    Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

  11. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  12. Mechanistic fracture criteria for the failure of human cortical bone

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    Nalla, Ravi K.; Kinney, John H.; Ritchie, Robert O.

    2002-12-13

    A mechanistic understanding of fracture in human bone is critical to predicting fracture risk associated with age and disease. Despite extensive work, a mechanistic framework for describing how the underlying microstructure affects the failure mode in bone is lacking.

  13. Birth weight and adult bone metabolism are unrelated

    DEFF Research Database (Denmark)

    Frost, Morten; Petersen, Inge Lund; Andersen, Thomas Levin;

    2013-01-01

    INTRODUCTION: Low birth weight (BW) has been associated with poor bone health in adulthood. The aim of this study was to investigate the association between BW and bone mass and metabolism in adult BW discordant monozygotic twins (MZ). METHODS: 153 BW extremely discordant MZ twin-pairs were...... individuals using regression analyses with or without adjustment for height, weight, age, sex, and intra-pair correlation. Within-pair differences were assessed using Student's T-test and fixed-regression models. RESULTS: BW was not associated with BTMs, LS-, TH-, FN- or WB-BMD, but BW was associated with WB......-BMC, and -WB-Area after adjustments. Compared to the co-twin, twins with the highest BW were heavier and taller in adulthood (Mean differences (SD): 3.0 (10.5) kg; 1.6 (2.6) cm, both p ...

  14. Quercetin-induced changes in femoral bone microstructure of adult male rabbits

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    Ramona Babosová

    2016-06-01

    Full Text Available Flavonoids are a group of plant metabolites with antioxidant effects. One of the most abundant flavonoids in the human diet is quercetin. It is found widely in fruits, vegetables and has a lot of beneficial effects on human health. Quercetin has a positive pharmacological effect on bone metabolism and it prevents the organism against bone loss. However, its impact on the size of basic structural units of the compact bone is still unknown. Therefore, the aim of present study was to investigate the impact of the quercetin on femoral bone microstructure in 5-month-old male rabbits. Five rabbits of Californian broiler line were randomly divided into two groups. In the experimental group (E group; n=3, animals were intramuscularly injected with quercetin at dose 1000 μg.kg-1 body weight (bw for 90 days, 3 times per week. Two rabbits without quercetin administration served as a control group (C group. According to our results, intramuscular application of quercetin had an insignificant effect on cortical bone thickness in male rabbits. In these rabbits, changes in qualitative histological characteristics were present in the middle part of the compacta, where primary vascular longitudinal bone tissue was present and expanded there from the periosteum. Also, a lower number of secondary osteons was found in these animals. From the histomorphometrical point of view, significantly decreased sizes of primary osteons' vascular canals and secondary osteons (p <0.05 were found in rabbits administered by quercetin. Our findings indicate that subchronic administration of quercetin at the dose used in our study had considerable impact on both qualitative and quantitative histological characteristics of the compact bone in adult male rabbits.

  15. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  16. Aging, human immunodeficiency virus, and bone health

    Directory of Open Access Journals (Sweden)

    Kim C Mansky

    2010-09-01

    Full Text Available Kim C ManskyDivision of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USAAbstract: Highly active antiretroviral therapy (HAART has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV. HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.Keywords: osteopenia, osteomalacia, osteoporosis, bisphosphonates, tenofovir, osteoimmunology

  17. Microtomography of the human tooth-alveolar bone complex

    Science.gov (United States)

    Dalstra, Michel; Cattaneo, Paolo M.; Beckmann, Felix; Sakima, Maurício T.; Lemor, Carsten; Laursen, Morten G.; Melsen, Birte

    2006-08-01

    In this study the structure of the adult human dentoalveolar process is examined using conventional and synchrotron radiation-based microtomography (SRμCT). Mandibular and maxillary segments containing two to five adjacent teeth were harvested at autopsy from 49 adult donors. These segments were embedded in blocks of methylmetacrylate and scanned using a conventional table-top μCT-scanner at a pixel size and slice thickness of 35 μm. A few segments were also scanned at a synchrotron facility at an initial pixel size of 16.4 μm, which was binned by a factor 2 to result in an effective voxel size of almost 32.8 μm. The three-dimensional reconstructions revealed how intricately the teeth are supported by the alveolar bone. Furthermore, this support is highly inhomogeneous with respect to the buccal, mesial, lingual and distal quadrants. Reflecting their various degrees of mineralization, tissues like bone, dentine, enamel and cementum, could well be identified, especially in the scans made with SRμCT. Despite comparable voxel sizes, the reconstructed data-sets obtained with conventional μCT were less detailed and somewhat fuzzy in appearance compared to the data-sets of SRμCT. However, for quantification of macroscopical features like the thickness of the alveolar wall or the presence of dehiscences/fenestrations this seemed sufficient.

  18. Restoration of a Critical Mandibular Bone Defect Using Human Alveolar Bone-Derived Stem Cells and Porous Nano-HA/Collagen/PLA Scaffold.

    Science.gov (United States)

    Wang, Xing; Xing, Helin; Zhang, Guilan; Wu, Xia; Zou, Xuan; Feng, Lin; Wang, Dongsheng; Li, Meng; Zhao, Jing; Du, Jianwei; Lv, Yan; E, Lingling; Liu, Hongchen

    2016-01-01

    Periodontal bone defects occur in a wide variety of clinical situations. Adult stem cell- and biomaterial-based bone tissue regeneration are a promising alternative to natural bone grafts. Recent evidence has demonstrated that two populations of adult bone marrow mesenchymal stromal cells (BMSCs) can be distinguished based on their embryonic origins. These BMSCs are not interchangeable, as bones preferentially heal using cells that share the same embryonic origin. However, the feasibility of tissue engineering using human craniofacial BMSCs was unclear. The goal of this study was to explore human craniofacial BMSC-based therapy for the treatment of localized mandibular defects using a standardized, minimally invasive procedure. The BMSCs' identity was confirmed. Scanning electron microscopy, a cell proliferation assay, and supernatant detection indicated that the nHAC/PLA provided a suitable environment for aBMSCs. Real-time PCR and electrochemiluminescence immunoassays demonstrated that osteogenic markers were upregulated by osteogenic preinduction. Moreover, in a rabbit critical-size mandibular bone defect model, total bone formation in the nHAC/PLA + aBMSCs group was significantly higher than in the nHAC/PLA group but significantly lower than in the nHAC/PLA + preinduced aBMSCs. These findings demonstrate that this engineered bone is a valid alternative for the correction of mandibular bone defects.

  19. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    Science.gov (United States)

    Priller, Josef

    2003-08-01

    While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction.

  20. Bone mineral density in adults with Down`s syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Angelopoulou, N.; Souftas, V.; Mandroukas, K. [Ergophysiology Lab., Aristotle Univ. of Thessaloniki, Thessaloniki (Greece); Sakadamis, A. [Medical School, Aristotle Univ. of Thessaloniki (Greece)

    1999-05-01

    The objective of the study was to elucidate if individuals with Down`s syndrome (DS) are likely to experience an increased risk of osteoporosis with advancing age, in addition to precocious aging and their skeletal anomalies. Bone mineral density (BMD) was measured in 22 home-reared adults (9 males and 13 females; age 26.22 {+-} 4.45 and 23.65 {+-} 3.23 years, respectively) by dual energy X-ray absorptiometry (DXA). The BMD of the second to fourth lumbar vertebrae was measured in posteroanterior projection and the mean density expressed as grams per square centimetre. The BMD of DS individuals was compared with 27 control subjects (12 males and 15 females) of the same age (age 24.16 {+-} 3.46 and 23.86 {+-} 2.92 years, respectively). The results showed that the BMD of the lumbar spine in the males as well as in the females with DS was significantly lower than that in their control counterparts (p < 0.001). Comparing the DS males with the females, the BMD was lower in the males at a level of 9 %. Factors that contribute to this disorder may be mainly the muscular hypotonia, the sedentary lifestyle and the accompanying diseases which frequently observed in the syndrome. Future studies must be focused on the biochemistry of bone metabolism, the evaluation of gonadal, thyroid and parathyroid function, and the genes of the extra chromosome 21. (orig.) With 1 tab., 21 refs.

  1. Fibrillin-1 microfibrils influence adult bone marrow hematopoiesis.

    Science.gov (United States)

    Smaldone, Silvia; Bigarella, Carolina L; Del Solar, Maria; Ghaffari, Saghi; Ramirez, Francesco

    2016-01-01

    We have recently demonstrated that fibrillin-1 assemblies regulate the fate of skeletal stem cells (aka, mesenchymal stem cells [MSCs]) by modulating TGFβ activity within the microenvironment of adult bone marrow niches. Since MSCs can also influence hematopoietic stem cell (HSC) activities, here we investigated adult hematopoiesis in mice with Cre-mediated inactivation of the fibrillin-1 (Fbn1) gene in the mesenchyme of the forming limbs (Fbn1(Prx1-/-) mice). Analyses of 3-month-old Fbn1(Prx1-/-) mice revealed a statistically significant increase of circulating red blood cells, which a differentiation assay correlated with augmented erythropoiesis. This finding, together with evidence of fibrillin-1 deposition in erythroblastic niches, supported the notion that this extracellular matrix protein normally restricts differentiation of erythroid progenitors. Whereas flow cytometry measurements identified a decreased HSC frequency in mutant relative to wild type mice, no appreciable differences were noted with regard to the relative abundance and differentiation potential of myeloid progenitor cells. Together these findings implied that fibrillin-1 normally promotes HSC expansion but does not influence cell lineage commitment. Since local TGFβ hyperactivity has been associated with abnormal osteogenesis in Fbn1(Prx1-/-) mice, 1-month-old mutant and wild type animals were systemically treated for 8weeks with either a pan-TGF-β-neutralizing antibody or an antibody of the same IgG1 isotype. The distinct outcomes of these pharmacological interventions strongly suggest that fibrillin-1 differentially modulates TGFβ activity in HSC vs. erythroid niches.

  2. Tea flavonoids for bone health: from animals to humans.

    Science.gov (United States)

    Shen, Chwan-Li; Chyu, Ming-Chien

    2016-10-01

    Osteoporosis is a skeletal disease characterized by a deterioration of bone mass and bone quality that predisposes an individual to a higher risk of fragility fractures. Emerging evidence has shown that the risk for low bone mass and osteoporosis-related fractures can be reduced by nutritional approaches aiming to improve bone microstructure, bone mineral density, and strength. Tea and its flavonoids, especially those of black tea and green tea, have been suggested to protect against bone loss and to reduce risk of fracture, due to tea's antioxidant and anti-inflammatory properties. Based on the results of animal studies, moderate intake of tea has shown to benefit bone health as shown by mitigation of bone loss and microstructural deterioration as well as improvement of bone strength and quality. Epidemiological studies have reported positive, insignificant, and negative impacts on bone mineral density at multiple skeletal sites and risk of fracture in humans with habitual tea consumption. There are limited human clinical trials that objectively and quantitatively assessed tea consumption and bone efficacy using validated outcome measures in a population at high risk for osteoporosis, along with safety monitoring approach. This review summarizes the current state of knowledge of laboratory animal research, epidemiological observational studies, and clinical trials assessing the skeletal effects of tea and its active flavonoids, along with discussion of relevant future directions in translational research.

  3. Fundamental ratios and logarithmic periodicity in human limb bones.

    Science.gov (United States)

    Pietak, Alexis; Ma, Siyan; Beck, Caroline W; Stringer, Mark D

    2013-05-01

    Fundamental mathematical relationships are widespread in biology yet there is little information on this topic with regard to human limb bone lengths and none related to human limb bone volumes. Forty-six sets of ipsilateral upper and lower limb long bones and third digit short bones were imaged by computed tomography. Maximum bone lengths were measured manually and individual bone volumes calculated from computed tomography images using a stereologic method. Length ratios of femur : tibia and humerus : ulna were remarkably similar (1.21 and 1.22, respectively) and varied little (bone volume ratios varied much more than upper limb ratios. The relationship between bone length and volume was found to be well described by power laws, with R(2) values ranging from 0.983 to 0.995. The most striking finding was a logarithmic periodicity in bone length moving from distal to proximal up the limb (upper limb λ = 0.72, lower limb λ = 0.93). These novel data suggest that human limb bone lengths and volumes follow fundamental and highly conserved mathematical relationships, which may contribute to our understanding of normal and disordered growth, stature estimation, and biomechanics.

  4. Human foot bones from Klasies River main site, South Africa.

    Science.gov (United States)

    Rightmire, G Philip; Deacon, H J; Schwartz, Jeffrey H; Tattersall, Ian

    2006-01-01

    The caves at Klasies River contain abundant archaeological evidence relating to human evolution in the late Pleistocene of southern Africa. Along with Middle Stone Age artifacts, animal bones, and other food waste, there are hominin cranial fragments, mandibles with teeth, and a few postcranial remains. Three foot bones can now be added to this inventory. An adult first metatarsal is similar in size and discrete anatomical features to those from Holocene burials in the Cape Province. A complete and well-preserved second metatarsal is especially long and heavy at midshaft in comparison to all Holocene and more recent South African homologues. A large fifth metatarsal is highly distinctive in its morphology. In overall size, these pedal elements resemble specimens from late Pleistocene sites in western Asia, but there are some differences in proportions. The fossils support earlier suggestions concerning a relatively high level of sexual dimorphism in the African Middle Stone Age population. Squatting facets on the two lateral metatarsals appear to indicate a high frequency of kneeling among members of this group. The new postcranial material also underlines the fact that the morphology of particular skeletal elements of some of the 100,000-year-old Klasies River individuals falls outside the range of modern variation.

  5. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

    Full Text Available The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs. In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  6. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Atul Kumar [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Gajiwala, Astrid Lobo [Tissue Bank, Tata Memorial Hospital, Parel, Mumbai 400012 (India); Rai, Ratan Kumar [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Khan, Mohd Parvez [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Singh, Chandan [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Barbhuyan, Tarun [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Vijayalakshmi, S. [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Chattopadhyay, Naibedya [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Sinha, Neeraj, E-mail: neerajcbmr@gmail.com [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Kumar, Ashutosh, E-mail: ashutoshk@iitb.ac.in [Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076 (India); Bellare, Jayesh R., E-mail: jb@iitb.ac.in [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076 (India)

    2016-05-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS® (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  7. Mechanisms by which nutritional disorders cause reduced bone mass in adults.

    Science.gov (United States)

    Miller, Karen K

    2003-03-01

    Nutritional disorders that cause bone loss in adults include disordered eating behaviors (female athlete triad and anorexia nervosa), gastrointestinal diseases (celiac sprue, inflammatory bowel disease, and other malabsorption syndromes), alcoholism, and hypervitaminosis A. These disorders exert their effects on bone through a number of mechanisms, including estrogen deficiency. Deficiencies of anabolic hormones may also be important, including insulin-like growth factor I (IGF-I), a nutritionally regulated bone trophic factor. In addition, low weight itself is a risk factor for bone loss and decreased bone formation. Reduced calcium and vitamin D availability, with resultant secondary hyperparathyroidism, is another important mechanism of bone loss in nutritional disorders. This review discusses nutritional causes of reduced bone mass in adults and how nutritional disorders exert deleterious effects on the skeleton.

  8. A re-evaluation of the premaxillary bone in humans.

    Science.gov (United States)

    Barteczko, K; Jacob, M

    2004-03-01

    ventral to dorsal and the intercalation of the vomer. Thus the premaxilla acts as a stabilizing element within the facial skeleton comparable with the keystone of a Roman arch. Furthermore, the significance of the premaxillary anlage for the closure of the palatine was documented by a synopsis made from a stage 16, 10.2 mm GL embryo to a 49 mm GL fetus. Finally the growth of the premaxilla is closely related to the development of the human face. Abnormal growth may be correlated to characteristic malformations such as protrusion, closed bite and prognathism. Concerning the relation of the premaxillary bone to cleft lip and palate we agree with others that the position of the clefts is not always identical with the incisive suture. This is proved by the double anlagen of an upper-outer incisor in a 55 mm fetus and an adult.

  9. Identification of molecular markers related to human alveolar bone cells and pathway analysis in diabetic patients.

    Science.gov (United States)

    Sun, X; Ren, Q H; Bai, L; Feng, Q

    2015-10-28

    Alveolar bone osteoblasts are widely used in dental and related research. They are easily affected by systemic diseases such as diabetes. However, the mechanism of diabetes-induced alveolar bone absorption remains unclear. This study systematically explored the changes in human alveolar bone cell-related gene expression and biological pathways, which may facilitate the investigation of its mechanism. Alveolar bone osteoblasts isolated from 5 male diabetics and 5 male healthy adults were cultured. Total RNA was extracted from these cells and subjected to gene microarray analysis. Differentially expressed genes were screened, and a gene interaction network was constructed. An enrichment pathway analysis was simultaneously performed on differentially expressed genes to identify the biological pathways associated with changes in the alveolar bone cells of diabetic humans. In total, we identified 147 mRNAs that were differentially expressed in diabetic alveolar bone cells (than in the normal cells; 91 upregulated and 36 downregulated mRNAs). The constructed co-expression network showed 3 pairs of significantly-expressed genes. High-enrichment pathway analysis identified 8 pathways that were affected by changes in gene expression; three of the significant pathways were related to metabolism (inositol phosphate metabolism, propanoate metabolism, and pyruvate metabolism). Here, we identified a few potential genes and biological pathways for the diagnosis and treatment of alveolar bone cells in diabetic patients.

  10. A simplified procedure for preparation of undecalcified human bone sections

    DEFF Research Database (Denmark)

    Wallin, J A; Tkocz, I; Levinsen, J

    1985-01-01

    A new type of apparatus for sectioning samples of hard, undecalcified bone is described. Slices of fresh or archeological human bone 4-5 mm thick are dehydrated and then embedded in epoxy resin. The apparatus used to prepare sections from the resulting blocks consists of a low-speed rim...

  11. Comparison of the relationship between bone marrow adipose tissue and volumetric bone mineral density in children and adults.

    Science.gov (United States)

    Shen, Wei; Velasquez, Gilbert; Chen, Jun; Jin, Ye; Heymsfield, Steven B; Gallagher, Dympna; Pi-Sunyer, F Xavier

    2014-01-01

    Several large-scale studies have reported the presence of an inverse relationship between bone mineral density (BMD) and bone marrow adipose tissue (BMAT) in adults. We aim to determine if there is an inverse relationship between pelvic volumetric BMD (vBMD) and pelvic BMAT in children and to compare this relationship in children and adults. Pelvic BMAT and bone volume (BV) was evaluated in 181 healthy children (5-17yr) and 495 healthy adults (≥18yr) with whole-body magnetic resonance imaging (MRI). Pelvic vBMD was calculated using whole-body dual-energy X-ray absorptiometry to measure pelvic bone mineral content and MRI-measured BV. An inverse correlation was found between pelvic BMAT and pelvic vBMD in both children (r=-0.374, pBMAT as the independent variable, being a child or adult neither significantly contribute to the pelvic BMD (p=0.995) nor did its interaction with pelvic BMAT (p=0.415). The inverse relationship observed between pelvic vBMD and pelvic BMAT in children extends previous findings that found the inverse relationship to exist in adults and provides further support for a reciprocal relationship between adipocytes and osteoblasts.

  12. Determinants of bone mass and bone geometry in adolescent and young adult women

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Hoorneman, G.; Väänänen, K.; Charles, P.; Ando, S.; Maggiolini, M.; Charzewska, J.; Rotily, M.; Deloraine, A.; Heikkinen, J.; Juvin, R.; Schaafsma, G.

    2000-01-01

    Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six

  13. Bioreactor cultivation of anatomically shaped human bone grafts.

    Science.gov (United States)

    Temple, Joshua P; Yeager, Keith; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana; Grayson, Warren L

    2014-01-01

    In this chapter, we describe a method for engineering bone grafts in vitro with the specific geometry of the temporomandibular joint (TMJ) condyle. The anatomical geometry of the bone grafts was segmented from computed tomography (CT) scans, converted to G-code, and used to machine decellularized trabecular bone scaffolds into the identical shape of the condyle. These scaffolds were seeded with human bone marrow-derived mesenchymal stem cells (MSCs) using spinner flasks and cultivated for up to 5 weeks in vitro using a custom-designed perfusion bioreactor system. The flow patterns through the complex geometry were modeled using the FloWorks module of SolidWorks to optimize bioreactor design. The perfused scaffolds exhibited significantly higher cellular content, better matrix production, and increased bone mineral deposition relative to non-perfused (static) controls after 5 weeks of in vitro cultivation. This technology is broadly applicable for creating patient-specific bone grafts of varying shapes and sizes.

  14. Limited Restoration of Cystic Fibrosis Lung Epithelium In Vivo with Adult Bone Marrow–derived Cells

    OpenAIRE

    Loi, Roberto; Beckett, Travis; Goncz, Kaarin K.; Suratt, Benjamin T.; Weiss, Daniel J.

    2005-01-01

    Rationale: Recent literature suggests that adult bone marrow–derived cells can localize to lung and acquire immunophenotypic characteristics of lung epithelial cells. We speculated this might be a potential therapeutic approach for correcting defective lung epithelium in cystic fibrosis.

  15. Bone mineral density, Bone mineral contents, MMP-8 and MMP-9 levels in Human Mandible and alveolar bone: Simulated microgravity

    Science.gov (United States)

    Rai, Balwant; Kaur, Jasdeep; Catalina, Maria

    Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. It has been reported that head-down tilt bed-rest studies mimic many of the observations seen in flights. There is no study on the correlation on effects of mandibular bone and alveolar bone loss in both sex in simulating microgravity. This study was designed to determine the Bone mineral density and GCF MMP-8 MMP-9 in normal healthy subject of both sexes in simulated microgravity condition of -6 head-down-tilt (HDT) bed rest. The subjects of this investigation were 10 male and 10 female volunteers participated in three weeks 6 HDT bed-rest exposure. The Bone density and bone mineral contents were measured by dual energy X-ray absorptiometry before and in simulated microgravity. The GCF MMP-8 MMP-8 were measured by Enzyme-linked immunosorbent assays (Human Quantikine MMP-8,-9 ELISA kit). The bone mineral density and bone mineral contents levels were significantly decreased in simulated microgravity condition in both genders, although insignificantly loss was higher in females as compared to males. MMP-8 MMP-9 levels were significantly increased in simulated microgravity as compared to normal condition although insignificantly higher in females as compared to males. Further study is required on large samples size including all factors effecting in simulated microgravity and microgravity. Keys words-Simulated microgravity condition, head-down-tilt, Bone loss, MMP-8, MMP-9, Bone density, Bone mineral contents.

  16. No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study

    DEFF Research Database (Denmark)

    Petruskevicius, Juozas; Nielsen, Mette Strange; Kaalund, Søren;

    2002-01-01

    We studied the effects of a newly marketed bone substitute, Osteoset, on bone healing in a tibial defect in humans. 20 patients undergoing an ACL (anterior cruciate ligament) reconstruction with bone-patella tendon-bone graft were block-randomized into 2 groups of 10 each. In the treatment group...

  17. Morphometric study of distance between posterior inferior iliac spine and ischial spine of the human hip bone for sex determination

    OpenAIRE

    2014-01-01

    Background: Objective of current study was to study the distance between Posterior Inferior Iliac Spine and Ischial Spine (PIIS-IS) of human hip bone for determination of sex. Methods: The study comprised unpaired 149 adult human hip bones of known sex. The posterior inferior iliac spine and ischial spine were identified in all the hip bones and a vernier calliper was used to measure the distance between the PIIS-IS. Results: It was observed that the mean distance of PIIS-IS in males a...

  18. Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical and pathological correlates.

    Science.gov (United States)

    van Dussen, L; Lips, P; van Essen, H W; Hollak, C E M; Bravenboer, N

    2014-09-01

    Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.

  19. Adult stem cells in the use of jaw bone regeneration: current and prospective research.

    Science.gov (United States)

    Zigdon-Giladi, Hadar; Khoury, Nizar; Evron, Ayelet

    2015-02-01

    Concomitant to the increased use of dental implants to replace lost dentition, there is a growing need to regenerate atrophic jaw bone to allow dental implant placement. Current surgical techniques for jaw bone augmentation share several limitations, such as operator sensitivity and relatively low predictability and high morbidity rates. Therefore, alternative treatment approaches have been developed in the field of tissue engineering. Bone tissue engineering integrates the use of different scaffolds, growth factors, and stem cells. This method aims to induce bone augmentation of large bone defects by mimicking biologic processes that occur during embryogenesis. This review will present available sources for adult stem cells, the rationale for using stem cells for bone regeneration, and recent studies that use mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) to induce bone augmentation.

  20. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  1. Unicameral bone cyst of the lunate in an adult: case report

    Directory of Open Access Journals (Sweden)

    Alici Tugrul

    2010-10-01

    Full Text Available Abstract We report a case of a symptomatic unicameral (simple bone cyst of the lunate in a 42-year- old woman. The lesion was treated with curettage and cancellous autogenous iliac bone grafting. At five years of follow-up the wrist was pain free, there were no limitations of motion, and the radiographs showed complete obliteration of the cavity. To the best of our knowledge, no other unicameral bone cyst of the lunate has been reported in an adult. Cysts with significant cavities at the carpal bones in an adult should be approached cautiously, as they may require early curettage and bone grafting for healing, before collapse and degenerative changes occur.

  2. Association between sleep duration, insomnia symptoms and bone mineral density in older Puerto Rican adults

    Science.gov (United States)

    Objective: To examine the association between sleep patterns (sleep duration and insomnia symptoms) and total and regional bone mineral density (BMD) among older Boston Puerto Rican adults. Materials/Methods: We conducted a cross-sectional study including 750 Puerto Rican adults, aged 47–79 y livi...

  3. Isoflavones prevent bone loss following ovariectomy in young adult rats

    Directory of Open Access Journals (Sweden)

    Chen Li-Ting

    2008-03-01

    Full Text Available Abstract Soy protein, a rich source of phytoestrogens, exhibit estrogen-type bioactivity. The purpose of this study was to determine if ingestion of isoflavones before ovariectomy can prevent bone loss following ovariectomy. Twenty-four nulliparous Wistar rats were randomly divided into four groups. In the normal diet groups, a sham operation was performed on Group A, while ovariectomy was performed on Group B. For Groups C and D, all rats were fed with an isoflavone-rich (25 mg/day diet for one month, then bilateral ovariectomy were performed. In the rats in Group C, a normal diet was begun following the ovariectomy. The rats in Groups D continued to receive the isoflavone-rich diet for two additional months postoperatively. All rats were sacrificed 60 days after surgery. The weight of bone ash of the long bones and whole lumbar spine were determined. A histological study of cancellous bone was done and biochemical indices of skeletal metabolism were performed and analyzed. The markers of bone metabolism exhibited no significant changes. When compared with the sham-operated rats fed a normal diet, the bone mass of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. The bone mass of rats treated with an isoflavone-rich diet for three months was higher than controls two months after ovariectomy. Dietary isoflavones did not prevent the development of post-ovariectomy bone loss, but long-term ingestion of an isoflavone-rich diet increased the bone mineral contents after ovariectomy in young rats.

  4. 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

  5. Evaluation of the osteogenesis and angiogenesis effects of erythropoietin and the efficacy of deproteinized bovine bone/recombinant human erythropoietin scaffold on bone defect repair.

    Science.gov (United States)

    Li, Donghai; Deng, Liqing; Xie, Xiaowei; Yang, Zhouyuan; Kang, Pengde

    2016-06-01

    Erythropoietin (EPO) could promote the angiogenesis and may also play a role in bone regeneration. This study was conducted to evaluate the osteogenesis and angiogenesis effects of EPO and the efficacy of deproteinized bovine bone/recombinant human EPO scaffold on bone defect repair. Twenty-four healthy adult goats were chosen to build goat defects model and randomly divided into four groups. The goats were treated with DBB/rhEPO scaffolds (group A), porous DBB scaffolds (group B), autogenous cancellous bone graft (group C), and nothing (group D). Animals were evaluated with radiological and histological methods at 4, 8 and 12 weeks after surgery. The grey value of radiographs was used to evaluate the healing of the defects and the outcome revealed that the group A had a better outcome of defect healing compared with group B (P 0.05). The newly formed bone area was calculated from histological sections and the results demonstrated that the amount of new bone in group A increased significantly compared with that in group B (P 0.05) at 4, 8, 12 weeks respectively. In addition, the expression of vascular endothelial growth factor (VEGF) by immunohistochemical testing and real-time polymerase chain reaction at 12 weeks in group A was significantly higher than that in group B (P 0.05). Therefore, EPO has significant effects on bone formation and angiogenesis, and has capacity to promote the repair of bone defects. It is worthy of being recommended to further studies.

  6. Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis.

    Science.gov (United States)

    Kün-Darbois, Jean-Daniel; Libouban, Hélène; Chappard, Daniel

    2015-08-01

    In man, botulinum toxin type A (BTX) is injected in masticatory muscles for several indications such as trismus, bruxism, or masseter hypertrophy. Bone changes in the mandible following BTX injections in adult animal have therefore became a subject of interest. The aim of this study was to analyze condylar and alveolar bone changes following BTX unilateral injections in masseter and temporal muscles in adult rats. Mature male rats (n = 15) were randomized into 2 groups: control (CTRL; n = 6) and BTX group (n= 9). Rats of the BTX group received a single injection of BTX into right masseter and temporal muscles. Rats of the CTRL group were similarly injected with saline solution. Rats were sacrificed 4 weeks after injections. Masticatory muscles examination and microcomputed tomography (microCT) were performed. A significant difference of weight was found between the 2 groups at weeks 2, 3 and 4 (p condylar areas in BTX rats. Decrease in bone volume reached -20% for right alveolar bone and -35% for right condylar bone. A hypertrophic bone metaplasia at the digastric muscle enthesis was found on every right hemimandible in the BTX group and none in the CTRL group. BTX injection in masticatory muscles leads to a significant and major mandible bone loss. These alterations can represent a risk factor for fractures in human. The occurrence of a hypertrophic bone metaplasia at the Mus Digastricus enthesis may constitute an etiological factor for tori.

  7. DNA and bone structure preservation in medieval human skeletons.

    Science.gov (United States)

    Coulson-Thomas, Yvette M; Norton, Andrew L; Coulson-Thomas, Vivien J; Florencio-Silva, Rinaldo; Ali, Nadir; Elmrghni, Samir; Gil, Cristiane D; Sasso, Gisela R S; Dixon, Ronald A; Nader, Helena B

    2015-06-01

    Morphological and ultrastructural data from archaeological human bones are scarce, particularly data that have been correlated with information on the preservation of molecules such as DNA. Here we examine the bone structure of macroscopically well-preserved medieval human skeletons by transmission electron microscopy and immunohistochemistry, and the quantity and quality of DNA extracted from these skeletons. DNA technology has been increasingly used for analyzing physical evidence in archaeological forensics; however, the isolation of ancient DNA is difficult since it is highly degraded, extraction yields are low and the co-extraction of PCR inhibitors is a problem. We adapted and optimised a method that is frequently used for isolating DNA from modern samples, Chelex(®) 100 (Bio-Rad) extraction, for isolating DNA from archaeological human bones and teeth. The isolated DNA was analysed by real-time PCR using primers targeting the sex determining region on the Y chromosome (SRY) and STR typing using the AmpFlSTR(®) Identifiler PCR Amplification kit. Our results clearly show the preservation of bone matrix in medieval bones and the presence of intact osteocytes with well preserved encapsulated nuclei. In addition, we show how effective Chelex(®) 100 is for isolating ancient DNA from archaeological bones and teeth. This optimised method is suitable for STR typing using kits aimed specifically at degraded and difficult DNA templates since amplicons of up to 250bp were successfully amplified.

  8. Determinants of microdamage in elderly human vertebral trabecular bone.

    Directory of Open Access Journals (Sweden)

    Hélène Follet

    Full Text Available Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53 from donors 54-95 years of age (22 men and 30 women, 1 unknown and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types.

  9. Bare Bones Young Adult Services: Tips for Public Library Generalists.

    Science.gov (United States)

    Vaillancourt, Renee J.

    This book is a hands-on guide to the philosophy and practice of young adult services in the public libraries. The following chapters are included: (1) "Young Adult Services Philosophy," including reasons to serve teens, why teens are the way they are, who serves young adults, and how to interact with teens; (2) "Youth Participation," including…

  10. Non-invasive photo acoustic approach for human bone diagnosis.

    Science.gov (United States)

    Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

    2016-12-01

    The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via

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

    DEFF Research Database (Denmark)

    Wong, Christian; Gehrchen, P Martin; Kiaer, Thomas

    2008-01-01

    A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws.......A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws....

  12. CXC receptor knockout mice: characterization of skeletal features and membranous bone healing in the adult mouse.

    Science.gov (United States)

    Bischoff, David S; Sakamoto, Taylor; Ishida, Kenji; Makhijani, Nalini S; Gruber, Helen E; Yamaguchi, Dean T

    2011-02-01

    The potential role of CXC chemokines bearing the glu-leu-arg (ELR) motif in bone repair was studied using a cranial defect (CD) model in mice lacking the CXC receptor (mCXCR(-/-) knockout mice), which is homologous to knockout of the human CXC receptor 2 (CXCR2) gene. During the inflammatory stage of bone repair, ELR CXC chemokines are released by inflammatory cells and serve as chemotactic and angiogenic factors. mCXCR(-/-) mice were smaller in weight and length from base of tail to nose tip, compared to WT littermates. DEXA analysis indicated that bone mineral density (BMD), bone mineral content (BMC), total area (TA), bone area (BA), and total tissue mass (TTM) were decreased in the mCXCR(-/-) mice at 6, 12, and 18 weeks of age. Trabecular bone characteristics in mCXCR(-/-) (% bone, connectivity, number, and thickness) were reduced, and trabecular spacing was increased as evidenced by μCT. There was no difference in bone formation or resorption indices measured by bone histomorphometry. Trabecular BMD was not altered. Cortical bone volume, BMD, and thickness were reduced; whereas, bone marrow volume was increased in mCXCR(-/-). Decreased polar moment of inertia (J) in the tibias/femurs suggested that the mCXCR(-/-) long bones are weaker. This was confirmed by three-point bending testing of the femurs. CDs created in 6-week-old male mCXCR(-/-) and WT littermates were not completely healed at 12 weeks; WT animals, however, had significantly more bone in-growth than mCXCR(-/-). New bone sites were identified using polarized light and assessed for numbers of osteocyte (OCy) lacunae and blood vessels (BlV) around the original CD. In new bone, the number of BlV in WT was >2× that seen in mCXCR(-/-). Bone histomorphometry parameters in the cranial defect did not show any difference in bone formation or resorption markers. In summary, studies showed that mCXCR(-/-) mice have (1) reduced weight and size; (2) decreased BMD and BMC; (3) decreased amounts of trabecular

  13. Harvesting olecranon bone graft in adults by using bone biopsy trephine

    Directory of Open Access Journals (Sweden)

    Fatih Kabakas

    2016-08-01

    Conclusion: Bone graft harvesting with trephine is technically easy and fast, and donor site morbidity is diminished compared other methods and donor sites. It can be performed under axillary anesthesia and provides adequate amounts of bone graft for upper extremity reconstructions. [Hand Microsurg 2016; 5(2.000: 44-49

  14. Human Bone Marrow Stromal Cells: A Reliable, Challenging Tool for In Vitro Osteogenesis and Bone Tissue Engineering Approaches

    Directory of Open Access Journals (Sweden)

    Ute Hempel

    2016-01-01

    Full Text Available Adult human bone marrow stromal cells (hBMSC are important for many scientific purposes because of their multipotency, availability, and relatively easy handling. They are frequently used to study osteogenesis in vitro. Most commonly, hBMSC are isolated from bone marrow aspirates collected in clinical routine and cultured under the “aspect plastic adherence” without any further selection. Owing to the random donor population, they show a broad heterogeneity. Here, the osteogenic differentiation potential of 531 hBMSC was analyzed. The data were supplied to correlation analysis involving donor age, gender, and body mass index. hBMSC preparations were characterized as follows: (a how many passages the osteogenic characteristics are stable in and (b the influence of supplements and culture duration on osteogenic parameters (tissue nonspecific alkaline phosphatase (TNAP, octamer binding transcription factor 4, core-binding factor alpha-1, parathyroid hormone receptor, bone gla protein, and peroxisome proliferator-activated protein γ. The results show that no strong prediction could be made from donor data to the osteogenic differentiation potential; only the ratio of induced TNAP to endogenous TNAP could be a reliable criterion. The results give evidence that hBMSC cultures are stable until passage 7 without substantial loss of differentiation potential and that established differentiation protocols lead to osteoblast-like cells but not to fully authentic osteoblasts.

  15. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Chunlei Miao

    2017-01-01

    Full Text Available Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious.

  16. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Science.gov (United States)

    Miao, Chunlei; Zhou, Lulu; Tian, Lufeng; Zhang, Yingjie; Zhang, Wei; Yang, Fanghong; Liu, Tianyi

    2017-01-01

    Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious. PMID:28210626

  17. Angiogenic properties of adult human thymus fat.

    Science.gov (United States)

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  18. Project Healthy Bones: An Osteoporosis Prevention Program for Older Adults.

    Science.gov (United States)

    Klotzbach-Shimomura, Kathleen

    2001-01-01

    Project Healthy Bones is a 24-week exercise and education program for older women and men at risk for or who have osteoporosis. The exercise component is designed to improve strength, balance, and flexibility. The education curriculum stresses the importance of exercise, nutrition, safety, drug therapy, and lifestyle factors. (SK)

  19. Bone Mass in Young Adults with down Syndrome

    Science.gov (United States)

    Guijarro, M.; Valero, C.; Paule, B.; Gonzalez-Macias, J.; Riancho, J. A.

    2008-01-01

    Background: Down syndrome (DS) is a frequent cause of intellectual disability. With the increasing life expectancy of these patients, concerns have been raised about the risk of osteoporosis. In fact, several investigators have reported a reduced bone mass in DS. However, the results may be confounded by comorbid diseases, and differences in…

  20. 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.

  1. Training human mesenchymal stromal cells for bone tissue engineering applications

    NARCIS (Netherlands)

    Doorn, J.

    2012-01-01

    Human mesenchymal stromal cells (hMSCs) are an interesting source for cell therapies and tissue engineering applications, because these cells are able to differentiate into various target tissues, such as bone, cartilage, fat and endothelial cells. In addition, they secrete a wide array of growth fa

  2. Ancient DNA in human bone remains from Pompeii archaeological site.

    Science.gov (United States)

    Cipollaro, M; Di Bernardo, G; Galano, G; Galderisi, U; Guarino, F; Angelini, F; Cascino, A

    1998-06-29

    aDNA extraction and amplification procedures have been optimized for Pompeian human bone remains whose diagenesis has been determined by histological analysis. Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid repeat sequences) have been performed and compared with anthropometric data on sexing.

  3. Age variations in the properties of human tibial trabecular bone

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Danielsen, CC;

    1997-01-01

    We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young's modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate...

  4. [Thermo-elastic stress analysis of human bones].

    Science.gov (United States)

    Krüger-Franke, M; Heiland, A; Plitz, W; Refior, H J

    1995-01-01

    The Thermoelastic Stress Analysis (THESA) is a widely used procedure in motorcar- and airplane engineering. This study investigated the reliability of THESA for stress analysis of human bone. A human femur was cyclic stressed and the resulting stress pattern was scanned from the surface of the bone by means of the thermoelastic stress measuring instrument SPATE 9000. To proof whether the scan of SPATE 9000 is equivalent to the stress distribution of human femur surface, strain gauges are used to control the results at two different regions of the femur diaphysis under equal but static conditions. It could be shown, that both measuring methods lead to corresponding results of stress pattern on human femur surface.

  5. Stable isotopic analysis on ancient human bones in Jiahu site

    Institute of Scientific and Technical Information of China (English)

    HU YaoWu; S.H.AMBROSE; WANG ChangSui

    2007-01-01

    Palaeodietary analysis is one of important topics in bioarchaeology field and has been paid great attention to by Chinese archaeometrists recently. Ancient human bones in Jiahu Site were analyzed by means of stable isotopes of C, N and 0.13 human bones were excluded from 28 bones for dietary reconstruction due to their unusual collagen contents, C and N contents, and C/N atomic ratios especially.δ13C(-20.37±0.53‰)in collagen of remaining samples showed that C3 food were consumed mainly, which is consistent of the archaeological findings that rice was the staple in Jiahu. According to the difference of δ15N and δ13C values in bone collagen, the samples can be classified into four clusters. The changes of δ15N values in bone collagen and δ13C values in hydroxylapatite through whole cultural phases indicated the transition from hunting to gathering and fishing to rice agriculture and animal domestication ultimately. Meanwhile, the δ18O change in hydroxylapatite showed that palaeoclimate was relatively constant during Jiahu culture.

  6. Ex Vivo Behaviour of Human Bone Tumor Endothelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Infante, Teresa [SDN-Foundation, Institute of Diagnostic and Nuclear Development, IRCCS, 80143 Naples (Italy); Cesario, Elena [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy); Gallo, Michele; Fazioli, Flavio [Division of Skeletal Muscles Oncology Surgery, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); De Chiara, Annarosaria [Anatomic Pathology Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Tutucci, Cristina; Apice, Gaetano [Medical Oncology of Bone and Soft Sarcoma tissues Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Nigris, Filomena de, E-mail: filomena.denigris@unina2.it [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy)

    2013-04-11

    Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and experimental research have proved that angiogenic pathways differ in each tumor type and stage. Here, for the first time, we characterize at the molecular and functional level tumor endothelial cells from human bone sarcomas at different stages of disease and with different histotypes. We selected a CD31{sup +} subpopulation from biopsies that displayed the capability to grow as adherent cell lines without vascular endothelial growth factor (VEGF). Our findings show the existence in human primary bone sarcomas of highly proliferative endothelial cells expressing CD31, CD44, CD105, CD146 and CD90 markers. These cells are committed to develop capillary-like structures and colony formation units, and to produce nitric oxide. We believe that a better understanding of tumor vasculature could be a valid tool for the design of an efficacious antiangiogenic therapy as adjuvant treatment of sarcomas.

  7. Stable isotopic analysis on ancient human bones in Jiahu site

    Institute of Scientific and Technical Information of China (English)

    S.H.AMBROSE

    2007-01-01

    Palaeodietary analysis is one of important topics in bioarchaeology field and has been paid great at- tention to by Chinese archaeometrists recently. Ancient human bones in Jiahu Site were analyzed by means of stable isotopes of C, N and O. 13 human bones were excluded from 28 bones for dietary re- construction due to their unusual collagen contents, C and N contents, and C/N atomic ratios espe- cially. δ 13C (-20.37±0.53‰) in collagen of remaining samples showed that C3 food were consumed mainly, which is consistent of the archaeological findings that rice was the staple in Jiahu. According to the difference of δ 15N and δ 13C values in bone collagen, the samples can be classified into four clusters. The changes of δ 15N values in bone collagen and δ 13C values in hydroxylapatite through whole cultural phases indicated the transition from hunting to gathering and fishing to rice agriculture and animal domestication ultimately. Meanwhile, the δ 18O change in hydroxylapatite showed that pa- laeoclimate was relatively constant during Jiahu culture.

  8. Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

    DEFF Research Database (Denmark)

    Hyldstrup, L; Conway, G S; Racz, K

    2012-01-01

    Growth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength....... INTRODUCTION: In young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions. METHODS...

  9. American alligator proximal pedal phalanges resemble human finger bones: Diagnostic criteria for forensic investigators.

    Science.gov (United States)

    Ferraro, Joseph V; Binetti, Katie M

    2014-07-01

    A scientific approach to bone and tooth identification requires analysts to pursue the goal of empirical falsification. That is, they may attribute a questioned specimen to element and taxon only after having ruled out all other possible attributions. This requires analysts to possess a thorough understanding of both human and non-human osteology, particularly so for remains that may be morphologically similar across taxa. To date, forensic anthropologists have identified several potential 'mimics' for human skeletal remains, including pig teeth and bear paws. Here we document another possible mimic for isolated human skeletal elements--the proximal pedal phalanges of American alligators (Alligator mississippiensis) closely resemble the proximal and intermediate hand phalanges of adult humans. We detail morphological similarities and differences between these elements, with the goal of providing sufficient information for investigators to confidently falsify the hypothesis that a questioned phalanx is derived from an American alligator.

  10. A method for estimating age of medieval sub-adults from infancy to adulthood based on long bone length

    DEFF Research Database (Denmark)

    Primeau, Charlotte; Friis, Laila Saidane; Sejrsen, Birgitte;

    2016-01-01

    on a modern population (Maresh: Human growth and development () pp 155-200), and, lastly, based on archeological data with known ages (Rissech et al.: Forensic Sci Int 180 () 1-9). As growth of long bones is known to be non-linear it was tested if the regression model could be improved by applying a quadratic...... model. RESULTS: Comparison between estimated ages revealed that the modern data result in lower estimated ages when compared to the Danish regression equations. The estimated ages using the Danish regression equations and the regression equations developed by Rissech et al. (Forensic Sci Int 180 () 1......OBJECTIVES: To develop a series of regression equations for estimating age from length of long bones for archaeological sub-adults when aging from dental development cannot be performed. Further, to compare derived ages when using these regression equations, and two other methods. MATERIAL...

  11. Ancient Human Bone Microstructure in Medieval England: Comparisons between Two Socio-Economic Groups.

    Science.gov (United States)

    Miszkiewicz, Justyna J; Mahoney, Patrick

    2016-01-01

    Understanding the links between bone microstructure and human lifestyle is critical for clinical and anthropological research into skeletal growth and adaptation. The present study is the first to report correspondence between socio-economic status and variation in bone microstructure in ancient humans. Products of femoral cortical remodeling were assessed using histological methods in a large human medieval sample (N = 450) which represented two distinct socio-economic groups. Osteonal parameters were recorded in posterior midshaft femoral sections from adult males (N = 233) and females (N = 217). Using univariate and multivariate statistics, intact, fragmentary, and osteon population densities, Haversian canal area and diameter, and osteon area were compared between the two groups, accounting for sex, age, and estimated femoral robusticity. The size of osteons and their Haversian canals, as well as osteon density, varied significantly between the socio-economic groups, although minor inconsistencies were observed in females. Variation in microstructure was consistent with historical textual evidence that describes differences in mechanical loading and nutrition between the two groups. Results demonstrate that aspects of ancient human lifestyle can be inferred from bone microstructure.

  12. Recent origin of low trabecular bone density in modern humans.

    Science.gov (United States)

    Chirchir, Habiba; Kivell, Tracy L; Ruff, Christopher B; Hublin, Jean-Jacques; Carlson, Kristian J; Zipfel, Bernhard; Richmond, Brian G

    2015-01-13

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations.

  13. Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells.

    NARCIS (Netherlands)

    Colak, D.; Mori, T.; Brill, M.S; Pfeifer, A.; Falk, S.; Deng, C.; Monteiro, R.; Mummery, C.L.; Sommer, L.; Gotz, M.

    2008-01-01

    In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cel

  14. Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

    Science.gov (United States)

    Teh, A; Bosco, J J; Leong, K W; Saw, M H; Menaka, N; Devashanti, P

    1997-03-01

    Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.

  15. Emerging bone problems in patients infected with human immunodeficiency virus.

    Science.gov (United States)

    Mondy, Kristin; Tebas, Pablo

    2003-04-01

    Recently, a high incidence of osteopenia and osteoporosis has been observed in individuals infected with human immunodeficiency virus (HIV). This problem appears to be more frequent in patients receiving potent antiretroviral therapy. Other bone-related complications in HIV-infected individuals, including avascular necrosis of the hip and compression fracture of the lumbar spine, have also been reported. People living with HIV have significant alterations in bone metabolism, regardless of whether they are receiving potent antiretroviral therapy. The underlying mechanisms to account for these observations remain unknown, although studies are underway to examine the relationship between the bone abnormalities and other complications associated with HIV and antiretroviral therapy. HIV-infected patients with osteopenia or osteoporosis should be treated similarly to HIV-seronegative patients with appropriate use of nutritional supplements (calcium and vitamin D) and exercise. Hormone replacement and antiresorptive therapies might be also indicated.

  16. Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: a cross-sectional long-term followup study

    DEFF Research Database (Denmark)

    Zak, M; Hassager, C; Lovell, D J

    1999-01-01

    To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD.......To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD....

  17. Intrusion of incisors in adult patients with marginal bone loss.

    Science.gov (United States)

    Melsen, B; Agerbaek, N; Markenstam, G

    1989-09-01

    Elongated and spaced incisors are common problems in patients suffering from severe periodontal disease. Thirty patients characterized by marginal bone loss and deep overbite were treated by intrusion of incisors. Three different methods for intrusion were applied: (1) J hooks and extraoral high-pull headgear, (2) utility arches, (3) intrusion bent into a loop in a 0.17 x 0.25-inch wire, and (4) base arch as described by Burstone. The intrusion was evaluated from the displacement of the apex, incision, and the center of resistance of the most prominent or elongated central incisor. Change in the marginal bone level and the amount of root resorption were evaluated on standardized intraoral radiographs. The pockets were assessed by standardized probing and the clinical crown length was measured on study casts. The results showed that the true intrusion of the center of resistance varied from 0 to 3.5 mm and was most pronounced when intrusion was performed with a base arch. The clinical crown length was generally reduced by 0.5 to 1.0 mm. The marginal bone level approached the cementoenamel junction in all but six cases. All cases demonstrated root resorption varying from 1 to 3 mm. The total amount of alveolar support--that is, the calculated area of the alveolar wall--was unaltered or increased in 19 of the 30 cases. The dependency of the results on the oral hygiene, the force distribution, and the perioral function was evaluated in relation to the individual cases. It was obvious that intrusion was best performed when (1) forces were low (5 to 15 gm per tooth) with the line of action of the force passing through or close to the center of resistance, (2) the gingiva status was healthy, and (3) no interference with perioral function was present.

  18. A pediatric bone mass scan has poor ability to predict adult bone mass: a 28-year prospective study in 214 children.

    Science.gov (United States)

    Buttazzoni, Christian; Rosengren, Bjorn E; Tveit, Magnus; Landin, Lennart; Nilsson, Jan-Åke; Karlsson, Magnus K

    2014-02-01

    As the correlation of bone mass from childhood to adulthood is unclear, we conducted a long-term prospective observational study to determine if a pediatric bone mass scan could predict adult bone mass. We measured cortical bone mineral content (BMC [g]), bone mineral density (BMD [g/cm(2)]), and bone width (cm) in the distal forearm by single photon absorptiometry in 120 boys and 94 girls with a mean age of 10 years (range 3-17) and mean 28 years (range 25-29) later. We calculated individual and age-specific bone mass Z scores, using the control cohort included at baseline as reference, and evaluated correlations between the two measurements with Pearson's correlation coefficient. Individual Z scores were also stratified in quartiles to register movements between quartiles from growth to adulthood. BMD Z scores in childhood and adulthood correlated in both boys (r = 0.35, p pediatric bone scan with a value in the lowest quartile had a sensitivity of 48% (95% confidence interval [CI] 27-69%) and a specificity of 76% (95% CI 66-84%) to identify individuals who would remain in the lowest quartile also in adulthood. Childhood forearm BMD explained 12% of the variance in adult BMD in men and 25% in women. A pediatric distal forearm BMD scan has poor ability to predict adult bone mass.

  19. Creep of trabecular bone from the human proximal tibia

    Energy Technology Data Exchange (ETDEWEB)

    Novitskaya, Ekaterina, E-mail: eevdokim@ucsd.edu [Mechanical and Aerospace Engineering, UC, San Diego, La Jolla, CA 92093 (United States); Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States); Zin, Carolyn [Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218 (United States); Chang, Neil; Cory, Esther; Chen, Peter [Departments of Bioengineering and Orthopaedic Surgery, UC, San Diego, La Jolla, CA 92093 (United States); D’Lima, Darryl [Shiley Center for Orthopaedic Research and Education, Scripps Health, La Jolla, CA 92037 (United States); Sah, Robert L. [Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States); Departments of Bioengineering and Orthopaedic Surgery, UC, San Diego, La Jolla, CA 92093 (United States); McKittrick, Joanna [Mechanical and Aerospace Engineering, UC, San Diego, La Jolla, CA 92093 (United States); Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States)

    2014-07-01

    Creep is the deformation that occurs under a prolonged, sustained load and can lead to permanent damage in bone. Creep in bone is a complex phenomenon and varies with type of loading and local mechanical properties. Human trabecular bone samples from proximal tibia were harvested from a 71-year old female cadaver with osteoporosis. The samples were initially subjected to one cycle load up to 1% strain to determine the creep load. Samples were then loaded in compression under a constant stress for 2 h and immediately unloaded. All tests were conducted with the specimens soaked in phosphate buffered saline with proteinase inhibitors at 37 °C. Steady state creep rate and final creep strain were estimated from mechanical testing and compared with published data. The steady state creep rate correlated well with values obtained from bovine tibial and human vertebral trabecular bone, and was higher for lower density samples. Tissue architecture was analyzed by micro-computed tomography (μCT) both before and after creep testing to assess creep deformation and damage accumulated. Quantitative morphometric analysis indicated that creep induced changes in trabecular separation and the structural model index. A main mode of deformation was bending of trabeculae. - Highlights: • Compressive creep tests of human trabecular bone across the tibia were performed. • The creep rate was found to be inversely proportional to the density of the samples. • μ-computed tomography before and after testing identified regions of deformation. • Bending of the trabeculae was found to be the main deformation mode.

  20. Calcium isotope ratios in animal and human bone

    Science.gov (United States)

    Reynard, L. M.; Henderson, G. M.; Hedges, R. E. M.

    2010-07-01

    Calcium isotopes in tissues are thought to be influenced by an individual's diet, reflecting parameters such as trophic level and dairy consumption, but this has not been carefully assessed. We report the calcium isotope ratios (δ 44/42Ca) of modern and archaeological animal and human bone ( n = 216). Modern sheep raised at the same location show 0.14 ± 0.08‰ higher δ 44/42Ca in females than in males, which we attribute to lactation by the ewes. In the archaeological bone samples the calcium isotope ratios of the herbivorous fauna vary by location. At a single site, the archaeological fauna do not show a trophic level effect. Humans have lower δ 44/42Ca than the mean site fauna by 0.22 ± 0.22‰, and the humans have a greater δ 44/42Ca range than the animals. No effect of sex or age on the calcium isotope ratios was found, and intra-individual skeletal δ 44/42Ca variability is negligible. We rule out dairy consumption as the main cause of the lower human δ 44/42Ca, based on results from sites pre-dating animal domestication and dairy availability, and suggest instead that individual physiology and calcium intake may be important in determining bone calcium isotope ratios.

  1. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S;

    1994-01-01

    the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4......Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...

  2. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S;

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  4. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals.

    Science.gov (United States)

    Mondy, Kristin; Yarasheski, Kevin; Powderly, William G; Whyte, Michael; Claxton, Sherry; DeMarco, Debra; Hoffmann, Mary; Tebas, Pablo

    2003-02-15

    The underlying mechanisms of several bone disorders in human immunodeficiency virus (HIV)-infected persons and any relation to antiretroviral therapy have yet to be defined. A longitudinal study was conducted to estimate the prevalence of osteopenia or osteoporosis in HIV-infected persons; to assess bone mineralization, metabolism, and histomorphometry over time; and to evaluate predisposing factors. A total of 128 patients enrolled the study, and 93 were observed for 72 weeks. "Classic" risk factors (low body mass index, history of weight loss, steroid use, and smoking) for low bone mineral density (BMD) and duration of HIV infection were strongly associated with osteopenia. There was a weak association between low BMD and receipt of treatment with protease inhibitors; this association disappeared after controlling for the above factors. Markers of bone turnover tended to be elevated in the whole cohort but were not associated with low BMD. BMD increased slightly during follow-up. Traditional risk factors and advanced HIV infection play a more significant pathogenic role in the development of osteopenia and osteoporosis associated with HIV infection than do treatment-associated factors.

  5. Subchondral bone density distribution in the human femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Wright, David A.; Meguid, Michael; Lubovsky, Omri; Whyne, Cari M. [Sunnybrook Research Institute, Orthopaedic Biomechanics Laboratory, Toronto, Ontario (Canada)

    2012-06-15

    This study aims to quantitatively characterize the distribution of subchondral bone density across the human femoral head using a computed tomography derived measurement of bone density and a common reference coordinate system. Femoral head surfaces were created bilaterally for 30 patients (14 males, 16 females, mean age 67.2 years) through semi-automatic segmentation of reconstructed CT data and used to map bone density, by shrinking them into the subchondral bone and averaging the greyscale values (linearly related to bone density) within 5 mm of the articular surface. Density maps were then oriented with the center of the head at the origin, the femoral mechanical axis (FMA) aligned with the vertical, and the posterior condylar axis (PCA) aligned with the horizontal. Twelve regions were created by dividing the density maps into three concentric rings at increments of 30 from the horizontal, then splitting into four quadrants along the anterior-posterior and medial-lateral axes. Mean values for each region were compared using repeated measures ANOVA and a Bonferroni post hoc test, and side-to-side correlations were analyzed using a Pearson's correlation. The regions representing the medial side of the femoral head's superior portion were found to have significantly higher densities compared to other regions (p < 0.05). Significant side-to-side correlations were found for all regions (r {sup 2} = 0.81 to r {sup 2} = 0.16), with strong correlations for the highest density regions. Side-to-side differences in measured bone density were seen for two regions in the anterio-lateral portion of the femoral head (p < 0.05). The high correlation found between the left and right sides indicates that this tool may be useful for understanding 'normal' density patterns in hips affected by unilateral pathologies such as avascular necrosis, fracture, developmental dysplasia of the hip, Perthes disease, and slipped capital femoral head epiphysis. (orig.)

  6. A Crust-based Method of Reconstructing Human Bone

    Institute of Scientific and Technical Information of China (English)

    MA Shu-chao; LIU Yi

    2014-01-01

    We present a crust-based procedure for modeling human being’s bone, which is based on voronoi diagram and its dual, Delaunay triangulation. In three-dimensional space, the crust algorithm can generate a 3D-model using a set of sample points. The purposes of this paper is to extract precise contour from CT series, then refer to these contours as sample points, and then apply the crust algorithm to these sample points to get three dimensional mesh.

  7. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    Energy Technology Data Exchange (ETDEWEB)

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  8. Plastic Fibula Bone Deformity with Ipsilateral Fracture of Tibiain Adults: A Case Report

    OpenAIRE

    Abbas Abdoli Tafti; Sanazsadat Sajadi; Maryam Shahmoradi

    2015-01-01

    Plastic bowing is a constant deformation of long bones occurring after a long standing force to bone. This type of fracture is seen in children and is uncommon in the adults. In this paper we report a case of fibular plastic deformity with ipsilateral tibia fracture in a 20 years old man that occurred after a direct hit. At the initial examination vital signs were stable and radiography of tibia and fibula fracture with plastic deformation were clear. In order to treat him we performed fib...

  9. Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    Denmark, DenmarkAbstractReplacement of extensive local bone loss especially in revision joint arthroplasty and spine fusion is a significant clinical challenge. Allograft and autograft have been considered as gold standard for bone replacement. However, there are several disadvantages such as donor site...... from human tissue were included (IsoTis OrthoBiologics, Inc. USA). Both materials are commercially available. Titanium alloy implants (Biomet Inc.) of 10 mm in length and 10 mm in diameter were inserted bilaterally into the femoral condyles of 8 skeletally mature sheep. Thus four implants...... with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: DBM; DBM/CB with ratio of 1/3; DBM/allograft with ratio of 1/3; or allograft (Gold standard), respectively. Standardised surgical procedure was used1. At sacrifice, 6 weeks after surgery, both distal femurs were harvested...

  10. Building bones in babies: can and should we exceed the human milk-fed infant's rate of bone calcium accretion?

    Science.gov (United States)

    Increasing calcium absorption and bone calcium accretion to levels above those achieved by human milk-fed, full-term infants is possible with infant formulas. However, no data support such a goal or suggest that it is beneficial to short- or long-term bone health. Small differences in the bioavailab...

  11. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  12. Latent inhibition in human adults without masking.

    Science.gov (United States)

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  13. Aerobic Exercise and Whole-Body Vibration in Offsetting Bone Loss in Older Adults

    Directory of Open Access Journals (Sweden)

    Pei-Yang Liu

    2011-01-01

    Full Text Available Osteoporosis and its associated fractures are common complications of aging and most strategies to prevent and/or treat bone loss focused on antiresorptive medications. However, aerobic exercise (AEX and/or whole-body vibration (WBV might have beneficial effect on bone mass and provide an alternative approach to increase or maintain bone mineral density (BMD and reduce the risk of fractures. The purpose of this paper was to investigate the potential benefits of AEX and WBV on BMD in older population and discuss the possible mechanisms of action. Several online databases were utilized and based on the available literature the consensus is that both AEX and WBV may increase spine and femoral BMD in older adults. Therefore, AEX and WBV could serve as nonpharmacological and complementary approaches to increasing/maintaining BMD. However, it is uncertain if noted effects could be permanent and further studies are needed to investigate sustainability of either type of the exercise.

  14. Elastic Comparison Between Human and Bovine Femural Bone

    Directory of Open Access Journals (Sweden)

    Mohamed S. Gaith

    2012-12-01

    Full Text Available In this study, the elastic stiffness and the degree of anisotropy will be compared for the femur human and bovine bones are presented. A scale for measuring the overall elastic stiffness of the bone at different locations is introduced and its correlation with the calculated bulk modulus is analyzed. Based on constructing orthonormal tensor basis elements using the form-invariant expressions, the elastic stiffness for orthotropic system materials is decomposed into two parts; isotropic (two terms and anisotropic parts. The overall elastic stiffness is calculated and found to be directly proportional to bulk modulus. A scale quantitative comparison of the contribution of the anisotropy to the elastic stiffness and to measure the degree of anisotropy in an anisotropic material is proposed using the Norm Ratio Criteria (NRC. It is found that bovine femure plexiform has the largest overall elastic stiffness and bovine has the most isotropic (least anisotropic symmetry.

  15. First histological observations on the incorporation of a novel nanocrystalline hydroxyapatite paste OSTIM® in human cancellous bone

    Directory of Open Access Journals (Sweden)

    Huber Colette

    2006-06-01

    Full Text Available Abstract Background: A commercially available nanocrystalline hydroxyapatite paste Ostim® has been reported in few recent studies to surpass other synthetic bone substitutes with respect to the observed clinical results. However, the integration of this implantable material has been histologically evaluated only in animal experimental models up to now. This study aimed to evaluate the tissue incorporation of Ostim® in human cancellous bone after reconstructive bone surgery for trauma. Methods: Biopsy specimens from 6 adult patients with a total of 7 tibial, calcaneal or distal radial fractures were obtained at the time of osteosynthesis removal. The median interval from initial operation to tissue sampling was 13 (range 3–15 months. Samples were stained with Masson-Goldner, von Kossa, and toluidine blue. Osteoid volume, trabecular width and bone volume, and cortical porosity were analyzed. Samples were immunolabeled with antibodies against CD68, CD56 and human prolyl 4-hydroxylase to detect macrophages, osteoblasts, and fibroblasts, respectively. TRAP stainings were used to identify osteoclasts. Results: Histomorphometric data indicated good regeneration with normal bone turnover: mean osteoid volume was 1.93% of the trabecular bone mass, trabecular bone volume – 28.4%, trabecular width – 225.12 μm, and porosity index – 2.6%. Cortical and spongious bone tissue were well structured. Neither inflammatory reaction, nor osteofibrosis or osteonecrosis were observed. The implanted material was widely absorbed. Conclusion: The studied nanocrystalline hydroxyapatite paste showed good tissue incorporation. It is highly biocompatible and appears to be a suitable bone substitute for juxtaarticular comminuted fractures in combination with a stable screw-plate osteosynthesis.

  16. Comparative study on seeding methods of human bone marrow stromal cells in bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    齐欣; 刘建国; 常颖; 徐莘香

    2004-01-01

    Background In general the traditional static seeding method has its limitation while the dynamic seeding method reveals its advantages over traditional static method. We compared static and dynamic seeding method for human bone marrow stromal cells (hBMSCs) in bone tissue engineering.Methods DNA assay was used for detecting the maximal initial seeding concentration for static seeding. Dynamic and static seeding methods were compared, when scaffolds were loaded with hBMSCs at this maximal initial cell seeding concentration. Histology and scanning electron microscope (SEM) were examined to evaluate the distribution of cells inside the constructs. Markers encoding osteogenic genes were measured by fluorescent RT-PCR. The protocol for dynamic seeding of hBMSCs was also investigated.Results DNA assay showed that the static maximal initial seeding concentration was lower than that in dynamic seeding. Histology and SEM showed even distribution and spread of cells in the dynamically seeded constructs, while their statically seeded counterparts showed cell aggregation.Fluorescent RT-PCR again showed stronger osteogenic potential of dynamically seeded constructs.Conclusion dynamic seeding of hBMSCs is a promising technique in bone tissue engineering.

  17. Pulmonary Langerhans Cell Histiocytosis with Lytic Bone Involvement in an Adult Smoker: Regression following Smoking Cessation

    Directory of Open Access Journals (Sweden)

    B. Routy

    2015-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare myeloid neoplasm characterized by the proliferation and dissemination of histiocytes. These in turn may cause symptoms ranging from isolated, infiltrative lesions to severe multisystem disease. Pulmonary Langerhans cell histiocytosis (PLCH presents as a localized polyclonal proliferation of Langerhans cells in the lungs causing bilateral cysts and fibrosis. In adults, this rare condition is considered a reactive process associated with cigarette smoking. Recently, clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation in a subset of PLCH patients. Spontaneous resolution was described; however, based on case series, smoking cessation remains the most effective way to achieve complete remission and prevent long term complications related to tobacco. Herein, we report the case of an adult woman with biopsy-proven PLCH presenting with thoracic (T8 vertebral bone destruction. Both the lung and the bone diseases regressed following smoking cessation, representing a rare case of synchronous disseminated PCLH with bone localization. This observation underscores the contribution of cigarette smoking as a systemic trigger of both pulmonary and extrapulmonary bone lesions. A review of similar cases in the literature is also presented.

  18. Pulmonary Langerhans Cell Histiocytosis with Lytic Bone Involvement in an Adult Smoker: Regression following Smoking Cessation

    Science.gov (United States)

    Routy, B.; Hoang, J.; Gruber, J.

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the proliferation and dissemination of histiocytes. These in turn may cause symptoms ranging from isolated, infiltrative lesions to severe multisystem disease. Pulmonary Langerhans cell histiocytosis (PLCH) presents as a localized polyclonal proliferation of Langerhans cells in the lungs causing bilateral cysts and fibrosis. In adults, this rare condition is considered a reactive process associated with cigarette smoking. Recently, clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation in a subset of PLCH patients. Spontaneous resolution was described; however, based on case series, smoking cessation remains the most effective way to achieve complete remission and prevent long term complications related to tobacco. Herein, we report the case of an adult woman with biopsy-proven PLCH presenting with thoracic (T8) vertebral bone destruction. Both the lung and the bone diseases regressed following smoking cessation, representing a rare case of synchronous disseminated PCLH with bone localization. This observation underscores the contribution of cigarette smoking as a systemic trigger of both pulmonary and extrapulmonary bone lesions. A review of similar cases in the literature is also presented. PMID:25789184

  19. Bone Mineral Density and Body Composition of Adult Premenopausal Women with Three Levels of Physical Activity

    Directory of Open Access Journals (Sweden)

    Fernando D. Saraví

    2013-01-01

    Full Text Available Weight-bearing and resistance physical activities are recommended for osteoporosis prevention, but it is unclear whether an intensity level above current recommendations has a positive effect on adult premenopausal women. Body composition and bone mineral density (BMD by DXA were compared in three groups of women as follows: Sedentary, Maintenance exercise, and federated Sport Team (n=16 for each group. Physical activity was estimated from the International Physical Activity Questionnaire (IPAQ. The groups did not differ in age, height, weight, or body mass index. Bone mineral content and non-fat soft tissue mass were higher and fat mass was lower in the Sport Team group than in the other groups. The same was true for BMD of total skeleton, lumbar spine, femoral neck, and total hip. A test for linear trend of body composition and BMD showed significant results when including all three groups. Simple and multiple regression analyses showed significant associations between physical activity level (or alternatively, years of participation in programmed physical activity and bone mass measures at all sites except for the middle third of radius. It is concluded that a level of physical activity higher than that usually recommended benefits bone health in adult premenopausal women.

  20. Comparison in Adherence to Osteoporosis Guidelines according to Bone Health Status in Korean Adult

    OpenAIRE

    Lim, Hee-Sook; Kim, Soon-Kyung; Lee, Hae-Hyeog; Byun, Dong Won; Park, Yoon-Hyung; Kim, Tae-Hee

    2016-01-01

    Background Osteoporosis one of the most serious disease to decrease the quality of life and cause economic loss. Thus, prevention of osteoporosis has become an important health concern. The study examined in adherence to osteoporosis guidelines and compared the levels of adherence to osteoporosis guidelines between bone health status in Korean adult. Methods This study used data from a nationally represented sample of Koreans (n=3,419) from 2008 to 2011 Korea National Health and Nutrition Exa...

  1. Advancing maternal age is associated with lower bone mineral density in young adult male offspring

    OpenAIRE

    Rudäng, R.; Mellström, D.; Clark, E.; Ohlsson, C; Lorentzon, M.

    2011-01-01

    Summary Advancing maternal age has been related to increased risk of fetal death and morbidity, as well as higher fracture risk during childhood, in the offspring. In the present study, we demonstrate that advancing maternal age is independently associated with reduced bone mass in the young adult male offspring. Introduction In Sweden the maternal age in both primi- and multipara mothers has steadily increased during the last three decades. It has been previously reported that advancing mate...

  2. Effects of resistance training and protein supplementation on bone turnover in young adult women

    Directory of Open Access Journals (Sweden)

    Sinning Wayne E

    2005-08-01

    enhance bone formation or inhibit bone resorption in young adult women, as assessed by biochemical markers of bone metabolism. (2 Subsequent maintenance of a high protein intake for 10 days in these regularly-training, calcium-replete women also showed no effects on bone metabolism.

  3. Dietary Silicon Intake of Korean Young Adult Males and Its Relation to their Bone Status.

    Science.gov (United States)

    Choi, Mi-Kyeong; Kim, Mi-Hyun

    2017-03-01

    Accumulated data suggests a positive effect of silicon on bone health; however, limited research exists on the silicon content of foods. To further the understanding of the relationship between dietary silicon intake and bone health, a food composition database of commonly consumed foods in Korea is required. For quantitative data on the intake levels of silicon, we analyzed the silicon content of 365 food items commonly consumed in Korea using inductively coupled plasma-atomic emission spectrometry following microwave-assisted digestion. To investigate the dietary silicon intake status and to examine the potential role of dietary silicon intake in the bone status of men, a total of 400 healthy Korean adult males aged 19-25 were observed for their diet intake and calcaneus bone density using the 24-h recall method and quantitative ultrasound, respectively. Clinical markers reflecting bone metabolism such as serum total alkaline phosphatase, N-mid osteocalcin, and type 1 collagen C-terminal telopeptide concentrations were also analyzed. Silicon intake of the subjects was estimated as 37.5 ± 22.2 mg/day. Major food sources of dietary silicon in the Korean male were cereal and cereal products (25.6 % of total silicon intake), vegetables (22.7 %), beverages and liquors (21.2 %), and milk and milk products (7.0 %). Silicon intake correlated positively with age, weight, energy intake, protein intake, calcium intake, and alcohol intake. After adjusted for age, weight, energy intake, protein intake, calcium intake, alcohol intake, smoking cigarettes, and regular exercise status, daily total silicon intake had no correlation with calcaneus bone density and the bone metabolism markers, but silicon intake from vegetables had a positive correlation with serum total alkaline phosphatase activity, a bone formation maker. These findings show the possible positive relationship between dietary silicon intake from vegetables and the bone formation of young adult males. Further

  4. Translational Research: Palatal-derived Ecto-mesenchymal Stem Cells from Human Palate: A New Hope for Alveolar Bone and Cranio-Facial Bone Reconstruction.

    Science.gov (United States)

    Grimm, Wolf Dieter; Dannan, Aous; Giesenhagen, Bernd; Schau, Ingmar; Varga, Gabor; Vukovic, Mark Alexander; Sirak, Sergey Vladimirovich

    2014-05-01

    The management of facial defects has rapidly changed in the last decade. Functional and esthetic requirements have steadily increased along with the refinements of surgery. In the case of advanced atrophy or jaw defects, extensive horizontal and vertical bone augmentation is often unavoidable to enable patients to be fitted with implants. Loss of vertical alveolar bone height is the most common cause for a non primary stability of dental implants in adults. At present, there is no ideal therapeutic approach to cure loss of vertical alveolar bone height and achieve optimal pre-implantological bone regeneration before dental implant placement. Recently, it has been found that specific populations of stem cells and/or progenitor cells could be isolated from different dental resources, namely the dental follicle, the dental pulp and the periodontal ligament. Our research group has cultured palatal-derived stem cells (paldSCs) as dentospheres and further differentiated into various cells of the neuronal and osteogenic lineage, thereby demonstrating their stem cell state. In this publication will be shown whether paldSCs could be differentiated into the osteogenic lineage and, if so, whether these cells are able to regenerate alveolar bone tissue in vivo in an athymic rat model. Furthermore, using these data we have started a proof of principle clinical- and histological controlled study using stem cell-rich palatal tissues for improving the vertical alveolar bone augmentation in critical size defects. The initial results of the study demonstrate the feasibility of using stem cell-mediated tissue engineering to treat alveolar bone defects in humans.

  5. Bone Mineral Density in Adults With Down Syndrome, Intellectual Disability, and Nondisabled Adults

    Science.gov (United States)

    Geijer, Justin R.; Stanish, Heidi I.; Draheim, Christopher C.; Dengel, Donald R.

    2014-01-01

    Individuals with intellectual disability (ID) or Down syndrome (DS) may be at greater risk of osteoporosis. The purpose of this study was to compare bone mineral density (BMD) of DS, ID, and non-intellectually disabled (NID) populations. In each group, 33 participants between the ages of 28 and 60 years were compared. BMD was measured with…

  6. Bone marrow accumulation in gallium scintigraphy in patients with adult still's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanegae, Futoshi; Tada, Yoshifumi; Ohta, Akihide; Ushiyama, Osamu; Suzuki; Noriaki; Koarada, Syuichi; Haruta, Yoshio; Yoshikai, Tomonori; Nagasawa, Kohei [Saga Medical School (Japan)

    2002-12-01

    We investigated the features and the usefulness of gallium scintigraphy in the diagnosis and the assessment of Adult Still's disease (ASD) by retrospective case review. Gallium scintigraphy have been done for 11 cases of ASD (3 males and 8 females) and 4 females were positive. Among these, 67 Ga-citrate was accumulated to the bone marrow in all 4 cases and to the major joints in 2 cases. Positive cases were rather serious and administered more immunosuppressants than negative cases. In order to characterize gallium scintigraphy findings of ASD, i.e. bone marrow accumulation, we analyzed 130 cases of collagen vascular disease. Although 101 cases (77.7%) were positive, only 7 cases (5.4%) showed the accumulation of {sup 67}Ga-citrate to the bone marrow. These include 3 cases with ASD, and 1 case with systemic lupus erythematosus, polyarteritis nodosa, Wegener's granulomatosis and Sjogren's syndrome. We also accumulated 18 patients who exhibited bone marrow accumulation of {sup 69}Ga-citrate, and found that 7 patients had collagen vascular and their related diseases. In conclusion, bone marrow accumulation in gallium scintigraphy is a specific feature of collagen vascular diseases, especially ASD, and it is suggested that cases with positive gallium scintigraphy in ASD can be serious and resistant to treatment. (author)

  7. Qualitative and quantitative analysis of bones in adult rats by repeated intraperitoneal administration of paclitaxel (taxol) using radioisotope EDXRF technique

    Energy Technology Data Exchange (ETDEWEB)

    Oezdemir, Y. E-mail: yozdemir25@yahoo.com; Iyiguen, Ibrahim; Durak, Ridvan

    2003-05-15

    Energy dispersive X-ray fluorescence analysis of right back leg bone samples taken from adult female rats administered paclitaxel (taxol) was carried out using standard addition method. Because qualitative and quantitative data analysis of rat bone samples is not found in the literature, comparison was not made with other experimental results. Our experimental results are presented and discussed in this study.

  8. Bone mineral density in children and young adults with neurofibromatosis type 1.

    Science.gov (United States)

    Lodish, Maya B; Dagalakis, Urania; Sinaii, Ninet; Bornstein, Ethan; Kim, Aerang; Lokie, Kelsey B; Baldwin, Andrea M; Reynolds, James C; Dombi, Eva; Stratakis, Constantine A; Widemann, Brigitte C

    2012-12-01

    Concern for impaired bone health in children with neurofibromatosis type 1 (NF-1) has led to increased interest in bone densitometry in this population. Our study assessed bone mineral apparent density (BMAD) and whole-body bone mineral content (BMC)/height in pediatric patients with NF-1 with a high plexiform neurofibroma burden. Sixty-nine patients with NF-1 (age range 5.2-24.8; mean 13.7 ± 4.8 years) were studied. Hologic dual-energy X-ray absorptiometry scans (Hologic, Inc., Bedford, MA, USA) were performed on all patients. BMD was normalized to derive a reference volume by correcting for height through the use of the BMAD, as well as the BMC. BMAD of the lumbar spine (LS 2-4), femoral neck (FN), and total body BMC/height were measured and Z-scores were calculated. Impaired bone mineral density was defined as a Z-score ≤-2. Forty-seven percent of patients exhibited impaired bone mineral density at any bone site, with 36% at the LS, 18% at the FN, and 20% total BMC/height. BMAD Z-scores of the LS (-1.60 ± 1.26) were more impaired compared with both the FN (-0.54 ± 1.58; P=0.0003) and the whole-body BMC/height Z-scores (-1.16 ± 0.90; P=0.036). Plexiform neurofibroma burden was negatively correlated with LS BMAD (r(s)=-0.36, P=0.01). In pediatric and young adult patients with NF-1, LS BMAD was more severely affected than the FN BMAD or whole-body BMC/height.

  9. Have you got any cholesterol? Adults' views of human nutrition

    Science.gov (United States)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  10. Adult neurogenesis in humans- common and unique traits in mammals.

    Directory of Open Access Journals (Sweden)

    Aurélie Ernst

    2015-01-01

    Full Text Available New neurons are continuously generated in specific regions in the adult brain. Studies in rodents have demonstrated that adult-born neurons have specific functional features and mediate neural plasticity. Data on the extent and dynamics of adult neurogenesis in adult humans are starting to emerge, and there are clear similarities and differences compared to other mammals. Why do these differences arise? And what do they mean?

  11. Nanoscale Bonding between Human Bone and Titanium Surfaces: Osseohybridization

    Directory of Open Access Journals (Sweden)

    Jun-Sik Kim

    2015-01-01

    Full Text Available Until now, the chemical bonding between titanium and bone has been examined only through a few mechanical detachment tests. Therefore, in this study, a sandblasted and acid-etched titanium mini-implant was removed from a human patient after 2 months of placement in order to identify the chemical integration mechanism for nanoscale osseointegration of titanium implants. To prepare a transmission electron microscopy (TEM specimen, the natural state was preserved as much as possible by cryofixation and scanning electron microscope/focused ion beam (SEM-FIB milling without any chemical treatment. High-resolution TEM (HRTEM, energy dispersive X-ray spectroscopy (EDS, and scanning TEM (STEM/electron energy loss spectroscopic analysis (EELS were used to investigate the chemical composition and structure at the interface between the titanium and bone tissue. HRTEM and EDS data showed evidence of crystalline hydroxyapatite and intermixing of bone with the oxide layer of the implant. The STEM/EELS experiment provided particularly interesting results: carbon existed in polysaccharides, calcium and phosphorus existed as tricalcium phosphate (TCP, and titanium existed as oxidized titanium. In addition, the oxygen energy loss near edge structures (ELNESs showed a possibility of the presence of CaTiO3. These STEM/EELS results can be explained by structures either with or without a chemical reaction layer. The possible existence of the osseohybridization area and the form of the carbon suggest that reconsideration of the standard definition of osseointegration is necessary.

  12. SYNCHROTRON RADIATION XRF MICROPROBE STUDY OF HUMAN BONE TUMOR SLICE

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described Using the bovine liver as the standard reference.the minimum detection limit(MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe.The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated The experimental result relation to the clinical medicine was also discussed.

  13. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    Science.gov (United States)

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  14. Optimized Cryopreservation and Banking of Human Bone-Marrow Fragments and Stem Cells.

    Science.gov (United States)

    Carnevale, Gianluca; Pisciotta, Alessandra; Riccio, Massimo; De Biasi, Sara; Gibellini, Lara; Ferrari, Adriano; La Sala, Giovanni B; Bruzzesi, Giacomo; Cossarizza, Andrea; de Pol, Anto

    2016-04-01

    Adult mesenchymal stem cells are a promising source for cell therapies and tissue engineering applications. Current procedures for banking of human bone-marrow mesenchymal stem cells (hBM-MSCs) require cell isolation and expansion, and thus the use of large amounts of animal sera. However, animal-derived culture supplements have the potential to trigger infections and severe immune reactions. The aim of this study was to investigate an optimized method for cryopreservation of human bone-marrow fragments for application in cell banking procedures where stem-cell expansion and use are not immediately needed. Whole trabecular fragments enclosing the bone marrow were stored in liquid nitrogen for 1 year in a cryoprotective solution containing a low concentration of dimethyl sulfoxide and a high concentration of human serum (HuS). After thawing, the isolation, colony-forming-unit ability, proliferation, morphology, stemness-related marker expression, cell senescence, apoptosis, and multi-lineage differentiation potential of hBM-MSCs were tested in media containing HuS compared with hBM-MSCs isolated from fresh fragments. Human BM-MSCs isolated from cryopreserved fragments expressed MSC markers until later passages, had a good proliferation rate, and exhibited the capacity to differentiate toward osteogenic, adipogenic, and myogenic lineages similar to hBM-MSCs isolated from fresh fragments. Moreover, the cryopreservation method did not induce cell senescence or cell death. These results imply that minimal processing may be adequate for the banking of tissue samples with no requirement for the immediate isolation and use of hBM-MSCs, thus limiting cost and the risk of contamination, and facilitating banking for clinical use. Furthermore, the use of HuS for cryopreservation and expansion/differentiation has the potential for clinical application in compliance with good manufacturing practice standards.

  15. Bone loss in adult offspring induced by low-dose exposure to teratogens.

    Science.gov (United States)

    Torchinsky, Arkady; Mizrahi, Limor; Savion, Shoshana; Shahar, Ron; Toder, Vladimir; Kobyliansky, Eugene

    2012-05-01

    Maternal malnutrition during pregnancy was shown by numerous studies to result in the birth of offspring exhibiting altered bone characteristics, which are indicative of bone loss. We hypothesized that not only maternal malnutrition but also some developmental toxicants (teratogens) given at a dose inducing neither structural anomalies nor growth retardation can detrimentally affect skeletal health in adult offspring. To check this hypothesis, pregnant mice were exposed to a single injection of 5-aza-2-deoxycytidine (5-AZA) (a teratogen capable of inducing phocomelia of the hind limbs) at a sub-threshold teratogenic dose. Micro-computed tomography scanning revealed that femora of 5-month-old male offspring exposed in uterus to 5-AZA had trabecular microarchitecture indicative of bone loss. Furthermore, exposure to 5-AZA increased the susceptibility of offspring to postnatal chronic mild stress, which has been shown to induce bone loss in mice. While exploring possible mechanisms underlying this phenomenon, we observed that the expression of some microRNAs, which have been demonstrated as regulators of key osteoblastogenic genes, was altered in hind limb buds of embryos exposed to 5-AZA. Furthermore, the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in femoral stromal/osteoblastic cells of 5-month-old offspring of 5-AZA-treated females was found to be increased. Collectively, this study implies for the first time that single low-dose exposure to a teratogen can induce bone loss in adult offspring, possibly via alteration of embryonic microRNAs and RANKL expression.

  16. Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

    Science.gov (United States)

    Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

    2016-01-01

    This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations.

  17. Bone regenerative properties of rat, goat and human platelet-rich plasma.

    NARCIS (Netherlands)

    Plachokova, A.S.; Dolder, J. van den; Beucken, J.J.J.P. van den; Jansen, J.A.

    2009-01-01

    To explore the reported contradictory osteogenic capacity of platelet-rich plasma (PRP), the aim of the study was to examine and compare the bone regenerative effect of: PRPs of different species (rat, goat, human); human bone graft (HB) vs. HB combined with human PRP (HB+hPRP); and HB+hPRP vs. synt

  18. The dynamics of adult neurogenesis in human hippocampus.

    Science.gov (United States)

    Ihunwo, Amadi O; Tembo, Lackson H; Dzamalala, Charles

    2016-12-01

    The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis in humans and makes comparison to animal data.

  19. Validation of adult height prediction based on automated bone age determination in the Paris Longitudinal Study of healthy children

    Energy Technology Data Exchange (ETDEWEB)

    Martin, David D. [Tuebingen University Children' s Hospital, Tuebingen (Germany); Filderklinik, Filderstadt (Germany); Schittenhelm, Jan [Tuebingen University Children' s Hospital, Tuebingen (Germany); Thodberg, Hans Henrik [Visiana, Holte (Denmark)

    2016-02-15

    An adult height prediction model based on automated determination of bone age was developed and validated in two studies from Zurich, Switzerland. Varied living conditions and genetic backgrounds might make the model less accurate. To validate the adult height prediction model on children from another geographical location. We included 51 boys and 58 girls from the Paris Longitudinal Study of children born 1953 to 1958. Radiographs were obtained once or twice a year in these children from birth to age 18. Bone age was determined using the BoneXpert method. Radiographs in children with bone age greater than 6 years were considered, in total 1,124 images. The root mean square deviation between the predicted and the observed adult height was 2.8 cm for boys in the bone age range 6-15 years and 3.1 cm for girls in the bone age range 6-13 years. The bias (the average signed difference) was zero, except for girls below bone age 12, where the predictions were 0.8 cm too low. The accuracy of the BoneXpert method in terms of root mean square error was as predicted by the model, i.e. in line with what was observed in the Zurich studies. (orig.)

  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. The relevance of mouse models for investigating age-related bone loss in humans.

    Science.gov (United States)

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  2. Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

    Science.gov (United States)

    Cobb, Kensi M.; Stuart, Andrew

    2016-01-01

    Purpose The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Method Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level…

  3. Role of purinergic receptor polymorphisms in human bone

    DEFF Research Database (Denmark)

    Wesselius, Anke; Bours, Martijn J L; Agrawal, Ankita;

    2011-01-01

    receptor subtypes have been identified on bone cells. Several cellular functions in bone tissue are coupled to P2-receptor activation, including bone resorption, cytokine release, apoptosis, bone formation, and mineral deposition. Furthermore, ATP release and P2 purinergic signalling is a key pathway...

  4. Low Bone Mineral Density in Chinese Adults with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Ran Cui

    2013-01-01

    Full Text Available Aim. To investigate bone metabolic characteristics in Chinese adults with nonalcoholic fatty liver disease (NAFLD. Methods. A total of 224 patients (99 males and 125 postmenopausal females were recruited and divided into 4 groups: males without NAFLD, males with NAFLD, females without NAFLD, and females with NAFLD. Bone mineral density (BMD was evaluated according to body mass index (BMI, waist circumference (WC, and serum biomarkers. β cell function was evaluated by HOMA2%B, HOMA2%S, and HOMA2IR. Results. Males in the NAFLD group had lower BMD of the right hip and the femoral neck (0.852±0.117 versus 0.930±0.123, P=0.002; 0.736±0.119 versus 0.812±0.132, P=0.004, and females had lower BMD of the right hip (0.725±0.141 versus 0.805±0.145, P=0.002 even after adjusted for weight, BMI, waist, HDL, and ALT. There was no significant difference in bone metabolic markers between patients with and without NAFLD. NAFLD was an important factor that affected the bone; moreover, the effect attenuated when HOMA2IR entered into the model (R2=0.160, β=−0.172, and P=0.008. Conclusions. NAFLD exerts a detrimental effect on BMD in both males and females. Insulin resistance may play an important role in this pathophysiological process.

  5. Adult Human Neurogenesis: from Microscopy to Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Amanda eSierra

    2011-04-01

    Full Text Available Neural stem cells reside in well-defined areas of the adult human brain and are capable of gene-rating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

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

    Directory of Open Access Journals (Sweden)

    Henk-Jan Prins

    2014-03-01

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

  7. 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.

  8. Pediatric and adult MRI atlas of bone marrow. Normal appearances, variants and diffuse disease states

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Sundaram, Murali [Cleveland Clinic Lerner College of Medicine, OH (United States); Cleveland Clinic Department of Radiology, OH (United States)

    2016-08-01

    This comprehensive atlas is unique in being devoted to the MRI appearances of bone marrow in the axial and appendicular skeleton of adults and children. Normal MRI findings, including common variants and degenerative changes, are first documented. MRI appearances in the entire spectrum of neoplastic and non-neoplastic infiltrative marrow disorders are then presented, with accompanying explanatory text. Among the conditions considered are multiple myeloma, the acute and chronic leukemias, diffuse metastases, diffuse lymphomas, the anemias, polycythemia vera, myelofibrosis, storage disorders, and infections. Characteristic changes to bone marrow following various forms of treatment are also displayed and discussed. The selected images reflect the use of a variety of sequences and techniques, such as fat suppression, and contrast-enhanced imaging.

  9. Building bones in babies: can and should we exceed the human milk-fed infant's rate of bone calcium accretion?

    Science.gov (United States)

    Abrams, Steven A

    2006-11-01

    Increasing calcium absorption and bone calcium accretion to levels above those achieved by human milk-fed, full-term infants is possible with infant formulas. However, no data support such a goal or suggest that it is beneficial to short- or long-term bone health. Small differences in the bioavailability of calcium between infant formulas are unlikely to have long-term consequences. Long-term studies of the effects of infant feeding type on ultimate bone mass are needed. For now, the vitamin-replete breast-fed infant's rate of calcium accretion during the first year of life should be the standard targeted for infant formulas.

  10. Bone marrow derived cells and alternative pathways of oogenesis in adult rodents.

    Science.gov (United States)

    Bukovsky, Antonin; Ayala, Maria E; Dominguez, Roberto; Svetlikova, Marta; Selleck-White, Rachel

    2007-09-15

    Oocyte generation in adult mouse ovaries by putative germ cells (PGCs) in bone marrow and peripheral blood has recently been proposed. It, however, remains unclear whether in laboratory rodents the PGCs reside in BM or the BM cells stimulate oogenesis from ovarian stem cells. We utilized immunoperoxidase staining to localize PGCs, oocytes, and BM derived cells in ovaries of adult (age 45-60 days) control and neonatally estrogenized rat females. In controls, BM derived cells accompanied emergence of PGCs from the ovarian surface epithelium (OSE) cells. The PGCs divided symmetrically, separated, and formed primordial follicles. A proportion (50%) of adult neonatally estrogenized rats lacked OSE. They exhibited occurrence of numerous BM derived cells and appearance of PGC precursors in the medulla. In juxtaposed deep ovarian cortex the emerging PGCs exhibited distinct pseudopodia and apparently migrated toward the mid cortex, where numerous primordial follicles were found. These observations indicate that BM derived cells accompany origination of PGCs from the OSE stem cells in normal adult rat females and from the medullary precursors in the adult neonatally estrogenized rats lacking OSE. An alternative origin of PGCs from the medullary region may explain why ovaries with destructed OSE are still capable of forming new primordial follicles.

  11. Correlation of vitamin D, bone mineral density and parathyroid hormone levels in adults with low bone density

    Directory of Open Access Journals (Sweden)

    Sunil Kota

    2013-01-01

    Full Text Available Background: Bone mineral densiy (BMD is known to be affected by serum 25-hydroxyvitamin D (25(OH D levels, intact parathyroid hormone (iPTH levels. Indian data pertinent to above observation is scant. Our study aimed to investigate the relationships between serum 25-hydroxyvitamin D (25(OH D levels, intact parathyroid hormone (iPTH levels and bone mineral density (BMD in a cohort of Indian patients. Materials and Methods: Adults with or without fragility fractures with low BMD at the hip or lumbar spine were evaluated clinically along with laboratory investigations. T-scores of the hip and spine were derived from BMD-DEXA (dual-energy X-ray absorptiometry. Multivariate regression models were used to investigate the relationships between serum 25(OH D, iPTH and BMD. Results: Total of 102 patients (male:female = 38:64 with a mean age of 62.5 ± 6.4 years were included in the study. Forty-four patients had osteopenia. Osteoporosis was present in 58 patients. The mean values for serum 25(OH D and iPTH levels were 21.3 ± 0.5 ng/ml and 53.1 ± 22.3 pg/ml, respectively. In 84.3% of patients, serum 25(OH D levels were below 30 ng/ml (Normal = 30-74 ng/ml, confirming vitamin D deficiency. There was no association between 25(OH D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353, respectively. Both at the hip and lumbar spine; iPTH levels, male gender, body mass index (BMI and age were found to be significant predictors of BMD. Patients with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml, 25(OH D was negatively associated with iPTH (P = 0.041. Conclusion: Among our cohort of patients with low BMD, no direct relationship between serum 25(OH D levels and BMD was observed. However, a negative correlation between iPTH and 25(OH D at serum 25(OH D concentrations <30 ng/ml. Serum iPTH levels showed a significant negative association with BMD at the hip and lumbar spine. Our findings underscore the critical role of

  12. Inner ear contribution to bone conduction hearing in the human.

    Science.gov (United States)

    Stenfelt, Stefan

    2015-11-01

    Bone conduction (BC) hearing relies on sound vibration transmission in the skull bone. Several clinical findings indicate that in the human, the skull vibration of the inner ear dominates the response for BC sound. Two phenomena transform the vibrations of the skull surrounding the inner ear to an excitation of the basilar membrane, (1) inertia of the inner ear fluid and (2) compression and expansion of the inner ear space. The relative importance of these two contributors were investigated using an impedance lumped element model. By dividing the motion of the inner ear boundary in common and differential motion it was found that the common motion dominated at frequencies below 7 kHz but above this frequency differential motion was greatest. When these motions were used to excite the model it was found that for the normal ear, the fluid inertia response was up to 20 dB greater than the compression response. This changed in the pathological ear where, for example, otosclerosis of the stapes depressed the fluid inertia response and improved the compression response so that inner ear compression dominated BC hearing at frequencies above 400 Hz. The model was also able to predict experimental and clinical findings of BC sensitivity in the literature, for example the so called Carhart notch in otosclerosis, increased BC sensitivity in superior semicircular canal dehiscence, and altered BC sensitivity following a vestibular fenestration and RW atresia.

  13. STUDY OF NUTRIENT FORAMINA OF ADULT FEMORA WITH ITS CORRELATION TO LENGTH OF THE BONE

    Directory of Open Access Journals (Sweden)

    Deepa Bhat.

    2015-12-01

    Full Text Available Introduction: Femur is the most richly vascularised long bone which derives its nourishment from various arteries of the lower limb. The quantum of blood supply is determined by the number and calibre of these arteries. Shaft of this bone is supplied by the vessels from perforators of the thigh which gives nutrient branches to it. Femoral shaft fractures are severe disabling injuries that demand critical evaluation as to the method of treatment. Since the success of these operations depends on a minimal interference with the blood supply of the bone, the knowledge of anatomy of the nutrient vessels is of considerable importance. Materials and Methods: The study was conducted on 300 adult femora available in the department of Anatomy. The study was undertaken to collect information on the variations in number, location, size of the nutrient foramina and if correlation exists between the length of femur and number of nutrient foramina. Results: 60% of the bones had double, 39.33% had single and only 0.67% had single nutrient foramina (NF. 52% of them were on medial lip of linea aspera followed by 41%on lateral lip and the rest scattered. 80% of NF was located on upper and middle segments of shaft and very meagre number in lower segment. No correlation was noted between number of NF and length of the bone. Discussion and Conclusions: The findings in the present study are compared and analyzed with previous researchers. The magnitude of care to be imparted while dealing with fractures of femoral shaft is discussed. The detailed knowledge on vascular anatomy of shaft would allow surgeon to preserve them during procedures.

  14. Gustofacial and olfactofacial responses in human adults.

    Science.gov (United States)

    Weiland, Romy; Ellgring, Heiner; Macht, Michael

    2010-11-01

    Adults' facial reactions in response to tastes and odors were investigated in order to determine whether differential facial displays observed in newborns remain stable in adults who exhibit a greater voluntary facial control. Twenty-eight healthy nonsmokers (14 females) tasted solutions of PROP (bitter), NaCl (salty), citric acid (sour), sucrose (sweet), and glutamate (umami) differing in concentration (low, medium, and high) and smelled different odors (banana, cinnamon, clove, coffee, fish, and garlic). Their facial reactions were video recorded and analyzed using the Facial Action Coding System. Adults' facial reactions discriminated between stimuli with opponent valences. Unpleasant tastes and odors elicited negative displays (brow lower, upper lip raise, and lip corner depress). The pleasant sweet taste elicited positive displays (lip suck), whereas the pleasant odors did not. Unlike newborns, adults smiled with higher concentrations of some unpleasant tastes that can be regarded as serving communicative functions. Moreover, adults expressed negative displays with higher sweetness. Except for the "social" smile in response to unpleasant tastes, adults' facial reactions elicited by tastes and odors mostly correspond to those found in newborns. In conclusion, adults' facial reactions to tastes and odors appear to remain stable in their basic displays; however, some additional reactions might reflect socialization influences.

  15. Scanning electron microscopy of human cortical bone failure surfaces.

    Science.gov (United States)

    Braidotti, P; Branca, F P; Stagni, L

    1997-02-01

    Undecalcified samples extracted from human femoral shafts are fractured by bending and the fracture surfaces are examined with a scanning electron microscope (SEM). The investigation is performed on both dry and wet (hydrated with a saline solution) specimens. SEM micrographs show patterns in many respects similar to those observed in fractography studies of laminated fiber-reinforced synthetic composites. In particular, dry and wet samples behave like brittle and ductile matrix laminates, respectively. An analysis carried out on the basis of the mechanisms that dominate the fracture process of laminates shows that a reasonable cortical bone model is that of a laminated composite material whose matrix is composed of extracellular noncollagenous calcified proteins, and the reinforcement is constituted by the calcified collagen fiber system.

  16. Adult Literacy Education and Human Rights: A View from Afghanistan

    Science.gov (United States)

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  17. Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

  18. Bone mineral density in young adult women with congenital adrenal hyperplasia

    Directory of Open Access Journals (Sweden)

    Nishant Raizada

    2016-01-01

    Full Text Available Background: There is equipoise regarding the status of bone mineral density (BMD in patients with congenital adrenal hyperplasia (CAH, where patients need to be on long-term low-dose steroids. Objective: We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range. Subjects and Methods: Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison. Results: The BMD at hip (0.85 ± 0.02 g/cm2 in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029. BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057. The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range. There was no history of fractures in CAH. Conclusion: Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored.

  19. Relationship between mechanical properties and bone mineral density of human femoral bone retrieved from patients with osteoarthritis.

    Science.gov (United States)

    Haba, Yvonne; Lindner, Tobias; Fritsche, Andreas; Schiebenhöfer, Ann-Kristin; Souffrant, Robert; Kluess, Daniel; Skripitz, Ralf; Mittelmeier, Wolfram; Bader, Rainer

    2012-01-01

    The objective of this study was to analyse retrieved human femoral bone samples using three different test methods, to elucidate the relationship between bone mineral density and mechanical properties. Human femoral heads were retrieved from 22 donors undergoing primary total hip replacement due to hip osteoarthritis and stored for a maximum of 24 hours postoperatively at + 6 °C to 8 °C.Analysis revealed an average structural modulus of 232±130 N/mm(2) and ultimate compression strength of 6.1±3.3 N/mm(2) with high standard deviations. Bone mineral densities of 385±133 mg/cm(2) and 353±172 mg/cm(3) were measured using thedual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), respectively. Ashing resulted in a bone mineral density of 323±97 mg/cm(3). In particular, significant linear correlations were found between DXA and ashing with r = 0.89 (p < 0.01, n = 22) and between structural modulus and ashing with r = 0.76 (p < 0.01, n = 22).Thus, we demonstrated a significant relationship between mechanical properties and bone density. The correlations found can help to determine the mechanical load capacity of individual patients undergoing surgical treatments by means of noninvasive bone density measurements.

  20. 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...

  1. Human bone hardness seems to depend on tissue type but not on anatomical site in the long bones of an old subject.

    Science.gov (United States)

    Ohman, Caroline; Zwierzak, Iwona; Baleani, Massimiliano; Viceconti, Marco

    2013-02-01

    It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

  2. Demineralized bone matrix and human cancellous bone enhance fixation of porous-coated titanium implants in sheep

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    2016-01-01

    Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic potential and the risk of disease transmission are clinical challenges. The use of osteoinductive materials, such as demineralized bone...... of DBM alone, DBM with CB, or allograft on the fixation of porous-coated titanium implants. DBM100 and CB produced from human tissue were included. Both materials are commercially available. DBM granules are placed in pure DBM and do not contain any other carrier. Titanium alloy implants, 10 mm long × 10...... (gold standard), respectively. A standardized surgical procedure was used. At sacrifice 6 weeks after implantation, both distal femurs were harvested. The implant fixation was evaluated by mechanical push-out testing to test shear mechanical properties between implant and the host bone...

  3. Relation Between Ghrelin Hormone Levels and Bone Mineral Density in Normal Adults

    Directory of Open Access Journals (Sweden)

    Y Naghiaee

    2011-08-01

    Full Text Available Introduction: Ghrelin hormone is a polypeptide with 28 amino acids that is secreted along the gastrointestinal tract, mainly in fundus of stomach. Some physiological functions of ghrelin include increase of appetite and food intake, energy balance, stimulation of growth hormone secretion and heart output and decrease in blood pressure. Recently, relation of ghrelin and bone mineral density has been considered. Methods: This descriptive study included 33 adult persons above 20 years of age. Bone mineral density was determined with dual energy x-ray absorptiometry in femur and lumbar regions. T-score over than -1 was considered as normal case. Ghrelin levels were determined by ELISA method. Results: The mean of age, body mass index and serum ghrelin were 40±10.6years, 27±3.6 kg/m² and 100.5±128 pg/ml, respectively. Correlation of ghrelin and variables was not statistically significant except weight (p=0.05. Conclusion: Range of serum ghrelin levels varies with age. In the present research, there was no relationship between ghrelin levels and bone mineral density in femur and lumbar regions. More studies with larger number of samples are proposed.

  4. 1H MAS and 1H --> 31P CP/MAS NMR study of human bone mineral.

    Science.gov (United States)

    Kaflak-Hachulska, A; Samoson, A; Kolodziejski, W

    2003-11-01

    Chemical structure of human bone mineral was studied by solid-state nuclear magnetic resonance (NMR) with magic-angle spinning (MAS). Trabecular and cortical bone samples from adult subjects were compared with mineral standards: hydroxyapatite (HA), hydrated and calcined, carbonatoapatite of type B with 9 wt% of CO3(2-) (CHA-B), brushite (BRU) and mixtures of HA with BRU. Proton spectra were acquired with excellent spectral resolution provided by ultra-high speed MAS at 40 kHz. 2D 1H-31P NMR heteronuclear correlation was achieved by cross-polarization (CP) under fast MAS at 12 kHz. 31P NMR was applied with CP from protons under slow MAS at 1 kHz. Appearance of 31P rotational sidebands together with their CP kinetics were analyzed. It was suggested that the sidebands of CP spectra are particularly suitable for monitoring the state of apatite crystal surfaces. The bone samples appeared to be deficient in structural hydroxyl groups analogous to those in HA. We found no direct evidence that the HPO4(2-) brushite-like ions are present in bone mineral. The latter problem is extensively discussed in the literature. The study proves there is a similarity between CHA-B and bone mineral expressed by their similar NMR behavior.

  5. Engineering new bone via a minimally invasive route using human bone marrow-derived stromal cell aggregates, microceramic particles, and human platelet-rich plasma gel.

    Science.gov (United States)

    Chatterjea, Anindita; Yuan, Huipin; Fennema, Eelco; Burer, Ruben; Chatterjea, Supriyo; Garritsen, Henk; Renard, Auke; van Blitterswijk, Clemens A; de Boer, Jan

    2013-02-01

    There is a rise in the popularity of arthroscopic procedures in orthopedics. However, the majority of cell-based bone tissue-engineered constructs (TECs) rely on solid preformed scaffolding materials, which require large incisions and extensive dissections for placement at the defect site. Thus, they are not suitable for minimally invasive techniques. The aim of this study was to develop a clinically relevant, easily moldable, bone TEC, amenable to minimally invasive techniques, using human mesenchymal stromal cells (hMSCs) and calcium phosphate microparticles in combination with an in situ forming platelet-rich plasma gel obtained from human platelets. Most conventional TECs rely on seeding and culturing single-cell suspensions of hMSCs on scaffolds. However, for generating TECs amenable to the minimally invasive approach, it was essential to aggregate the hMSCs in vitro before seeding them on the scaffolds as unaggregated MSCs did not generate any bone. Twenty four hours of in vitro aggregation was determined to be optimal for maintaining cell viability in vitro and bone formation in vivo. Moreover, no statistically significant difference was observed in the amount of bone formed when the TECs were implanted via an open approach or a minimally invasive route. TECs generated using MSCs from three different human donors generated new bone through the minimally invasive route in a reproducible manner, suggesting that these TECs could be a viable alternative to preformed scaffolds employed through an open surgery for treating bone defects.

  6. HISTOLOGICAL SEXUAL DIFFERENCES IN ADULT HUMAN PARATHYROID GLANDS

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    Fating Anita

    2014-07-01

    Full Text Available CONTEXT (BACKGROUND: Increasing problems of calcium deficiency with physiological conditions like pregnancy, lactation etc. it becomes the need of time to focus attention towards these glands as one of the essential entity. Hence we have undertaken this study to have an idea about normal variation in the gland as per sex. AIMS: To reveal sexual differences in adult human parathyroid glands. METHODS AND MATERIAL: Parathyroid glands from 25 autopsied cases of 20 to 59 years were studied after staining with Hematoxylin & Eosin, Masson’s Trichrome & Reticulin stains. STATISTICAL ANALYSIS: Data is analyzed on statistical software intercooled STATA version 8.0. Data was presented in mean± standard deviation & categorical variables were expressed in percentages. Comparison of oxyphil scores in male & female was done by unpaired‘t’ test. P < 0.05 was taken as statistical significance. RESULTS: Stroma composed of short often branching reticular fibres along with blood vessels and fat cells. By statistical examination the amount of fat was more in case of females than in males of same age groups. Oxyphil cells being less numerous than chief cells were distinguished by their dark eosinophilic, granular cytoplasm and were arranged mostly in closely packed groups without interstitial fat in between the cells. Oxyphil cells also found as placed singly among chief cells. It was also observed as continuous masses or anastomosing columns. As compared with males oxyphil cells are more in females. CONCLUSIONS: By statistical analysis 1 Percentage of stromal fat in case of females was slightly greater than in males of same age group. 2 The score of oxyphil cells in females was double to more than triple as compared to male score of same age group. 3 This study is clinically important as hormonal changes occurs early in females than in males and it is in favor of providing supplementary calcium with D3 along with minimal dose of estrogen as age advances in

  7. Three-dimensional microstructure of human alveolar trabecular bone: a micro-computed tomography study

    Science.gov (United States)

    2017-01-01

    Purpose The microstructural characteristics of trabecular bone were identified using micro-computed tomography (micro-CT), in order to develop a potential strategy for implant surface improvement to facilitate osseointegration. Methods Alveolar bone specimens from the cadavers of 30 humans were scanned by high-resolution micro-CT and reconstructed. Volumes of interest chosen within the jaw were classified according to Hounsfield units into 4 bone quality categories. Several structural parameters were measured and statistically analyzed. Results Alveolar bone specimens with D1 bone quality had significantly higher values for all structural parameters than the other bone quality categories, except for trabecular thickness (Tb.Th). The percentage of bone volume, trabecular separation (Tb.Sp), and trabecular number (Tb.N) varied significantly among bone quality categories. Tb.Sp varied markedly across the bone quality categories (D1: 0.59±0.22 mm, D4: 1.20±0.48 mm), whereas Tb.Th had similar values (D1: 0.30±0.08 mm, D4: 0.22±0.05 mm). Conclusions Bone quality depended on Tb.Sp and number—that is, endosteal space architecture—rather than bone surface and Tb.Th. Regardless of bone quality, Tb.Th showed little variation. These factors should be taken into account when developing individualized implant surface topographies. PMID:28261521

  8. Is the corticomedullary index valid to distinguish human from nonhuman bones: a multislice computed tomography study.

    Science.gov (United States)

    Rérolle, Camille; Saint-Martin, Pauline; Dedouit, Fabrice; Rousseau, Hervé; Telmon, Norbert

    2013-09-10

    The first step in the identification process of bone remains is to determine whether they are of human or nonhuman origin. This issue may arise when only a fragment of bone is available, as the species of origin is usually easily determined on a complete bone. The present study aims to assess the validity of a morphometric method used by French forensic anthropologists to determine the species of origin: the corticomedullary index (CMI), defined by the ratio of the diameter of the medullary cavity to the total diameter of the bone. We studied the constancy of the CMI from measurements made on computed tomography images (CT scans) of different human bones, and compared our measurements with reference values selected in the literature. The measurements obtained on CT scans at three different sites of 30 human femurs, 24 tibias, and 24 fibulas were compared between themselves and with the CMI reference values for humans, pigs, dogs and sheep. Our results differed significantly from these reference values, with three exceptions: the proximal quarter of the femur and mid-fibular measurements for the human CMI, and the proximal quarter of the tibia for the sheep CMI. Mid-tibial, mid-femoral, and mid-fibular measurements also differed significantly between themselves. Only 22.6% of CT scans of human bones were correctly identified as human. We concluded that the CMI is not an effective method for determining the human origin of bone remains.

  9. Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available BACKGROUND: Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied. METHODOLOGY AND PRINCIPAL FINDINGS: In this report, we show that feeding a high quality diet supplemented with blueberries (BB to pre-pubertal rats throughout development or only between postnatal day 20 (PND20 and PND34 prevented ovariectomy (OVX-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation. CONCLUSIONS/SIGNIFICANCE: These results indicate: 1 a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2 the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

  10. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

    Science.gov (United States)

    Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

    2017-02-14

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  11. The three-dimensional microstructure of trabecular bone: Analysis of site-specific variation in the human jaw bone

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jo Eun; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul; Huh, Kyung Hoe [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Shin, Jae Myung [Dept. of Oral and Maxillofacial Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of); Oh, Sung Ook [A Plus Dental Clinic, Seoul (Korea, Republic of)

    2013-12-15

    This study was performed to analyze human maxillary and mandibular trabecular bone using the data acquired from micro-computed tomography (micro-CT), and to characterize the site-specific microstructures of trabeculae. Sixty-nine cylindrical bone specimens were prepared from the mandible and maxilla. They were divided into 5 groups by region: the anterior maxilla, posterior maxilla, anterior mandible, posterior mandible, and mandibular condyle. After the specimens were scanned using a micro-CT system, three-dimensional microstructural parameters such as the percent bone volume, bone specific surface, trabecular thickness, trabecular separation, trabecular number, structure model index, and degrees of anisotropy were analyzed. Among the regions other than the condylar area, the anterior mandibular region showed the highest trabecular thickness and the lowest value for the bone specific surface. On the other hand, the posterior maxilla region showed the lowest trabecular thickness and the highest value for the bone specific surface. The degree of anisotropy was lowest at the anterior mandible. The condyle showed thinner trabeculae with a more anisotropic arrangement than the other mandibular regions. There were microstructural differences between the regions of the maxilla and mandible. These results suggested that different mechanisms of external force might exist at each site.

  12. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia;

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin...... (human adult skin stromal cells, (hASSCs) and human new-born skin stromal cells (hNSSCs)) grew readily in culture and the growth rate was highest in hNSSCs and lowest in hATSCs. Compared with phenotype of hBM-MSC, all cell populations were CD34(-), CD45(-), CD14(-), CD31(-), HLA-DR(-), CD13(+), CD29...

  13. Ancient Human Bone Microstructure in Medieval England: Comparisons between Two Socio-Economic Groups

    OpenAIRE

    Miszkiewicz, Justyna J.; Mahoney, Patrick

    2016-01-01

    Understanding the links between bone microstructure and human lifestyle is critical for clinical and anthropological research into skeletal\\ud growth and adaptation. The present study is the first to report correspondence between socio-economic status and variation in bone microstructure\\ud in ancient humans. Products of femoral cortical remodeling were assessed using histological methods in a large human medieval\\ud sample (N:450) which represented two distinct socio-economic groups. Osteona...

  14. Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.

    Directory of Open Access Journals (Sweden)

    Kentaro Yoshioka

    Full Text Available Prep1, a TALE-family homeodomain transcription factor, has been demonstrated to play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis. In the present study, we generated hematopoietic- and endothelial cell-specific Prep1-deficient mice and demonstrated that expression of Prep1 in the hematopoietic cell compartment is not essential for either embryonic or adult hematopoiesis, although its absence causes significant hematopoietic abnormalities in the adult bone marrow. Loss of Prep1 promotes cell cycling of hematopoietic stem/progenitor cells (HSPC, leading to the expansion of the HSPC pool. Prep1 deficiency also results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation. Maturation of T cells and B cells is also perturbed in Prep-deficient mice. These findings provide novel insight into the pleiotropic roles of Prep1 in adult hematopoiesis that were unrecognized in previous studies using germline Prep1 hypomorphic mice.

  15. One Million Bones: Measuring the Effect of Human Rights Participation in the Social Work Classroom

    Science.gov (United States)

    McPherson, Jane; Cheatham, Leah P.

    2015-01-01

    This article describes the integration of human rights content and a national arts-activism initiative--One Million Bones--into a bachelor's-level macro practice class as a human rights teaching strategy. Two previously validated scales, the Human Rights Exposure (HRX) in Social Work and the Human Rights Engagement (HRE) in Social Work (McPherson…

  16. The effects of different maceration techniques on nuclear DNA amplification using human bone.

    Science.gov (United States)

    Lee, Esther J; Luedtke, Jennifer G; Allison, Jamie L; Arber, Carolyn E; Merriwether, D Andrew; Steadman, Dawnie Wolfe

    2010-07-01

    Forensic anthropologists routinely macerate human bone for the purposes of identity and trauma analysis, but the heat and chemical treatments used can destroy genetic evidence. As a follow-up to a previous study on nuclear DNA recovery that used pig ribs, this study utilizes human skeletal remains treated with various bone maceration techniques for nuclear DNA amplification using the standard Combined DNA Index System (CODIS) markers. DNA was extracted from 18 samples of human lower leg bones subjected to nine chemical and heat maceration techniques. Genotyping was carried out using the AmpFlSTR COfiler and AmpFlSTR Profiler Plus ID kits. Results showed that heat treatments via microwave or Biz/Na(2)CO(3) in sub-boiling water efficiently macerate bone and produce amplifiable nuclear DNA for genetic analysis. Long-term use of chemicals such as hydrogen peroxide is discouraged as it results in poor bone quality and has deleterious effects on DNA amplification.

  17. Effects of Escherichia Coli-derived Recombinant Human Bone Morphogenetic Protein-2 Loaded Porous Hydroxyaptite-based Ceramics on Calvarial Defect in Rabbits

    Science.gov (United States)

    Kim, Shin-Young; Lee, Youngkyun; Seo, Seung-Jun; Lim, Jae-Hong

    2017-01-01

    Background Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli (E. coli) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli-derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits. Methods Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone. Results HA-BMP showed significantly higher degree of bone formation compared with BO and HA group (Pceramics can promote new bone formation. PMID:28326298

  18. GATA1 mutation negative acute megakaryoblastic leukemia with acquired trisomy 21 presenting with extensive bone marrow necrosis in an adult: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Todd P. Williams

    2016-03-01

    Conclusions: To our knowledge, this is the first reported case of an adult with AMKL with acquired trisomy 21 in which the GATA1 mutation was investigated and the second reported case of AMKL presenting with extensive bone marrow necrosis. We will present a diagnostic approach to AMKL in which extensive bone marrow necrosis renders examination of the bone marrow difficult. Furthermore, we will examine the absence of the GATA1 mutation in a case of AMKL with trisomy 21 in an adult.

  19. Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

    NARCIS (Netherlands)

    S. James (Sally); J. Fox (James); F. Afsari (Farinaz); J. Lee (Jennifer); S. Clough (Sally); C. Knight (Charlotte); J. Ashmore (James); P. Ashton (Peter); O. Preham (Olivier); M.J. Hoogduijn (Martin); R.D.A.R. Ponzoni (Raquel De Almeida Rocha); Y. Hancock; M. Coles (Mark); P.G. Genever (Paul)

    2015-01-01

    textabstractBone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis

  20. Relation between in vitro and in vivo osteogenic potential of cultured human bone marrow stromal cells

    NARCIS (Netherlands)

    Mendes, SC; Tibbe, JM; Veenhof, M; Both, S; Oner, FC; van Blitterswijk, CA; de Bruijn, Joost D.

    2004-01-01

    The use of cell therapies in bone reconstruction has been the subject of extensive research. It is known that human bone marrow stromal cell (HBMSC) cultures contain a population of progenitor cells capable of differentiation towards the osteogenic lineage. In the present study, the correlation betw

  1. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    Science.gov (United States)

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  2. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults

    NARCIS (Netherlands)

    Boot, Annemieke M.; Krenning, Eric P.; Keizer-Schrama, Sabine M. P. F. de Muinck

    2011-01-01

    Objective: The associations between peak bone mineral density (BMD) and body composition with 25 hydroxyvitamin D (25OHD) levels in healthy young adults were evaluated. Methods: The number of participants was 464; 347 women and 117 men. The mean age was 24.3 years (range 17-31 years). BMD of the lum

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro

    Institute of Scientific and Technical Information of China (English)

    杨林; 陶天遵; 王新婷; 杜宁; 陈伟珍; 陶树清; 王志成; 吴丽萍

    2003-01-01

    Objective To observe the effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro. Methods Iliac trabecular bone specimens were obtained from adult patients undergoing necessary surgery. After the bone pieces were digested with collagenase-trypsin, osteoblasts were released and incubated at 37℃ in a relative humidity of 95% and 5% CO2. Then, the cells were purified, and their passages were given DMEM-F12 and fetal bovine serum medium. Subsequently, 10-8 mol/L dexamethasone was added into the culture medium to incubate the osteoblasts for three days, and the cells from control groups were incubated without any drugs. All cells were observed continually with phase contrast microscope and transmission electron microscope. Finally, apoptosis was detected by the use of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and biochemical indices, alkaline phosphatase (ALP) and osteocalcin (OCN) were used to determine the effects of dexamethasone on proliferation, differentiation and apoptosis of adult osteoblasts in vitro. Results In the adult osteoblasts obtained by collagenase-trypsin digestion, it achieved high survial, stable biochemical indices and excellent purification. Under the condition of dexamethasone 10-8 mol/L and osteoblasts 10 000/ml, there was significant promotion of ALP and OCN secretion without cell apoptosis.Conclusions Dexamethasone has a significant effect on the proliferation and differentiation of adult osteoblasts in vitro without apoptosis, and dexamethasone at the suggested concentration can be used as positive control in drug studies for osteoporosis treatment.

  5. Differentiated human stem cells resemble fetal, not adult, β cells.

    Science.gov (United States)

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  6. Screening, prevention and management of osteoporosis and bone loss in adult and pediatric hematopoietic cell transplant recipients.

    Science.gov (United States)

    McClune, B L; Polgreen, L E; Burmeister, L A; Blaes, A H; Mulrooney, D A; Burns, L J; Majhail, N S

    2011-01-01

    Long-term survivors of hematopoietic cell transplantation (HCT) are at risk for loss of bone mineral density (BMD) and subsequent osteoporosis. There is a lack of clear guidelines for the screening, prevention and treatment of bone loss after HCT. We reviewed the prevailing literature and provide guidelines developed by our center for the screening and management of this complication. Bone loss occurs predominantly within the first 6-12 months after autologous and allogeneic HCT. Recovery first occurs in the lumbar spine and is followed by a slower recovery of BMD in the femoral neck. BMD may not return to baseline levels in patients with continuing exposure to corticosteroids and calcineurin inhibitors. All HCT recipients should be advised general interventions to reduce fracture risk including adequate intake of calcium and vitamin D. We recommend screening all adult allogeneic and autologous HCT recipients with dual-energy X-ray absorptiometry 1 year after transplantation. Patients at high risk for bone loss (for example, patients receiving ≥ 5 mg of prednisone equivalent daily for > 3 months) can be screened earlier (for example, 3-6 months after HCT). Where indicated, bisphosphonates or other anti-resorptive agents (for example, calcitonin) can be used for prevention or treatment of osteoporosis in adult HCT recipients. Pediatric HCT recipients should be referred to a pediatric endocrinologist for evaluation and treatment of bone loss. There remain several areas of uncertainty that need further research in adult and pediatric HCT recipients, such as the optimal timing and frequency of screening for loss of bone mineral density, relationship of bone loss with risk of fractures, selection of appropriate patients for pharmacologic therapy, and optimal dosing schedule and duration of therapy with anti-resorptive agents.

  7. Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

    Science.gov (United States)

    Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

    2011-03-01

    Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

  8. Human embryonic and fetal mesenchymal stem cells differentiate toward three different cardiac lineages in contrast to their adult counterparts.

    Science.gov (United States)

    Ramkisoensing, Arti A; Pijnappels, Daniël A; Askar, Saïd F A; Passier, Robert; Swildens, Jim; Goumans, Marie José; Schutte, Cindy I; de Vries, Antoine A F; Scherjon, Sicco; Mummery, Christine L; Schalij, Martin J; Atsma, Douwe E

    2011-01-01

    Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.

  9. AGE-RELATED CHANGES OF BONE MARROW OF NORMAL ADULT MAN ON DIFFUSION WEIGHTED IMAGING

    Institute of Scientific and Technical Information of China (English)

    Chun-yan Zhang; Rong Rong; Xiao-ying Wang

    2008-01-01

    Objective To investigate the signal intensity and apparent diffusion coefficient (ADC) of bone marrow of normal adult man on diffusion weighted imaging (DWI).Methods Fifteen healthy volunteers and thirty-eight patients with benign prostatic hyperplasia or normal prostate were enrolled in this study, with age range 28-82 years old (mean 55.26 ± 18.05 years). All people were examined with large field DWI on a 3.0T magnetic resonance scanner, which ranges from the top of head to the lower limb. The signal-to-noise ratio (SNR) on the DWI and ADC of lumber vertebra at renal hilum level, left ilium and superior segment of left femur were measured. The measured SNR and ADC value of the above sites were compared by one way analysis of variance and their correlations with age were investigated by Pearson's correlation analysis. Results The SNR of lumber vertebra, left ilium and left femur showed no significant difference (F = 0.271, P = 0.763). The SNR of lumber vertebra (r = 0.309, P = 0.024) and left ilium (r = 0.359, P = 0.008) showed positive correlation with age, while the SNR of left femur showed no correlation with age (r = -0.163, P = 0.283). The ADC of lumber vertebra [(0.617 ± 0.177) ×10-3 mm2/s] was significantly higher than that of left ilium [(0.404 ± 0.112)×10-3 mm2/ P < 0.001] and left femur [(0.362 ± 0.092)×10-3mm2/s, P < 0.001], while the ADC of left ilium and left femur had no significant difference. The ADC of lumber vertebra, left ilium and left femur showed no correlation with age. Conclusion Understanding of age-related changes of normal adult bone marrow on DWI is very important to differentiate the normal bone marrow and abnormal lesions.

  10. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by means...... normal donors aged 16-83 years were tested in compression. The deformation was measured simultaneously in bone and cartilage to obtain the mechanical properties of both tissues. RESULTS: The stiffnesses and elastic energies of both cartilage and bone showed an initial increase, with maxima at 40 years......, followed by a steady decline. The viscoelastic energy was maximal at younger ages (16-29 years), followed by a steady decline. The energy absorption capacity did not vary with age. Stiffnesses and elastic energies were correlated significantly between cartilage and bone. CONCLUSIONS: The present study...

  11. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    Science.gov (United States)

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.

  12. Study on the Microstructure of Human Articular Cartilage/Bone Interface

    Institute of Scientific and Technical Information of China (English)

    Yaxiong Liu; Qin Lian; Jiankang He; Jinna Zhao; Zhongmin Jin; Dichen Li

    2011-01-01

    For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope (SEM), histological sections and MicroCT were used to observe, measure and model the microstructure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified cartilage and subchondral bone are in the manner of"protrusion-pore" with average diameter of 17.0 μm and 34.1 μm respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

  13. Adult mesenchymal stem cells for bone and cartilage engineering: effect of scaffold materials

    Directory of Open Access Journals (Sweden)

    A Gigante

    2009-08-01

    Full Text Available Bone marrow is a useful cell source for skeletal tissue engineering approaches. In vitro differentiation of marrow mesenchymal stem cells (MSCs to chondrocytes or osteoblasts can be induced by the addition of specific growth factors to the medium. The present study evaluated the behaviour of human MSCs cultured on various scaffolds to determine whether their differentiation can be induced by cell-matrix interactions. MSCs from bone marrow collected from the acetabulum during hip arthroplasty procedures were isolated by cell sorting, expanded and characterised by a flow cytometry system. Cells were grown on three different scaffolds (type I collagen, type I + II collagen and type I collagen + hydroxyapatite membranes and analysed by histochemistry, immunohistochemistry and spectrophotometry (cell proliferation, alkaline phosphatase activity at 15 and 30 days. Widely variable cell adhesion and proliferation was observed on the three scaffolds. MSCs grown on type I+II collagen differentiated to cells expressing chondrocyte markers, while those grown on type I collagen + hydroxyapatite differentiated into osteoblast-like cells. The study highlighted that human MSCs grown on different scaffold matrices may display different behaviours in terms of cell proliferation and phenotype expression without growth factor supplementation.

  14. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells

    OpenAIRE

    Islam, Mohammad S; Stemig, Melissa E.; Takahashi, Yutaka; Hui, Susanta K.

    2014-01-01

    Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harv...

  15. Effects of intermittent negative pressure on osteogenesis in human bone marrow-derived stroma cells

    Institute of Scientific and Technical Information of China (English)

    Zhi YANG; Miao LIU; Yin-gang ZHANG; Xiong GUO; Peng XU

    2009-01-01

    Objective: We investigated the effects of intermittent negative pressure on osteogenesis in human bone marrow-derived stroma cells (BMSCs) in vitro. Methods: BMSCs were isolated from adult marrow donated by a hip osteoarthritis patient with prosthetic replacement and cultured in vitro. The third passage cells were divided into negative pressure treatment group and control group. The treatment group was induced by negative pressure intermittently (pressure: 50 kPa, 30 rain/times, and twice daily). The control was cultured in conventional condition. The osteogenesis of BMSCs was examined by phase-contrast mi-croscopy, the determination of alkaline phosphatase (ALP) activities, and the immunohistochemistry of collagen type I. The mRNA expressions of osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) in BMSCs were analyzed by real-time poly-merase chain reaction (PCR). Results: BMSCs showed a typical appearance of osteoblast after 2 weeks of induction by intermit-tent negative pressure, the activity of ALP increased significantly, and the expression of collagen type 1 was positive. In the treatment group, the mRNA expression of OPG increased significantly (P<0.05) and the mRNA expression of OPGL decreased significantly (P<0.05) after 2 weeks, compared with the control. Conclusion: Intermittent negative pressure could promote os-teogenesis in human BMSCs in vitro.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

  17. INCIDENCE OF WORMIAN BONE IN HUMAN SKULLS IN RAJAST HAN

    Directory of Open Access Journals (Sweden)

    William F.

    2013-02-01

    Full Text Available ABSTRACT: Wormian bones are formations associated with insuff icient growth at suture closure and are regarded as epigenetic and hypostatic traits. There exists racial variation in its incidence. AIM : To find the incidence of wormian bone and compare with other study. MATERIAL AND METHOD : This was autopsy study on 150 dead bodies of both sexes of all age groups. RESULT - Incidence of wormian bone in Rajasthan was 4.7 % (4.1% in males & 3.6 % in females. This is comparable with study in other par t of India & abroad and it is in accordance with racial variation. CONCLUSION - knowledge of wormian bone is important to neuroanatomist, neurosurgeon, radiologist, anthropol ogist and morphologist

  18. Analysis of fatty acid composition in human bone marrow aspirates.

    Science.gov (United States)

    Deshimaru, Ryota; Ishitani, Ken; Makita, Kazuya; Horiguchi, Fumi; Nozawa, Shiro

    2005-09-01

    In the present study, the fatty acid composition of bone marrow aspirates and serum phospholipids in nine patients with hematologic diseases was investigated, and the effect of fatty acids on osteoblast differentiation in ST2 cells was examined. The concentrations of oleic acid and palmitic acid were significantly higher in bone marrow aspirates than in serum phospholipids, but the concentrations of other fatty acids did not differ. The rate of alkaline phosphatase positive ST2 cells induced by BMP2 was significantly increased by oleic acid, but was unaffected by the presence or absence of palmitic acid. We conclude that the fatty acid composition of bone marrow aspirates differs from that of serum phospholipids. This difference may affect osteoblast differentiation in the bone marrow microenvironment.

  19. First forensic records of termite activity on non-fossilized human bones in Brazil

    Directory of Open Access Journals (Sweden)

    R. A. Queiroz

    Full Text Available Abstract The aim of this study was to describe the first records of termite activity on non-fossilized human bones in Brazil. The cases reported in this study resulted from forensic analysis of six human skeletons found in northeastern Brazil between 2012 and 2014. Traces of tunnels and nests commonly produced by termites were found on several human bone surfaces as well as the specimens and characteristic signs of osteophagic activity. In four cases, the species were identified: Amitermes amifer Silvestri, 1901, Nasutitermes corniger (Motschulsky, 1855 (on two skeletons, and Microcerotermes indistinctus Mathews, 1977. In two other cases, the activity of termites on bone surfaces was evidenced by remains of nests and tunnels produced by these insects. At least in the samples of human remains available for this report, the number of termites collected was greater on bones found during autumn, the rainy season in the Northeast of Brazil. The human bones examined showed termites like insects with lots of strength at bone degradation, capable of continuing the process of decomposition of human remains even in completely skeletonized bodies.

  20. First forensic records of termite activity on non-fossilized human bones in Brazil.

    Science.gov (United States)

    Queiroz, R A; Soriano, E P; Carvalho, M V D; Caldas-Junior, A F; Souza, E H A; Coelho-Junior, L G T M; Campello, R I C; Almeida, A C; Farias, R C A P; Vasconcellos, A

    2016-07-25

    The aim of this study was to describe the first records of termite activity on non-fossilized human bones in Brazil. The cases reported in this study resulted from forensic analysis of six human skeletons found in northeastern Brazil between 2012 and 2014. Traces of tunnels and nests commonly produced by termites were found on several human bone surfaces as well as the specimens and characteristic signs of osteophagic activity. In four cases, the species were identified: Amitermes amifer Silvestri, 1901, Nasutitermes corniger (Motschulsky, 1855) (on two skeletons), and Microcerotermes indistinctus Mathews, 1977. In two other cases, the activity of termites on bone surfaces was evidenced by remains of nests and tunnels produced by these insects. At least in the samples of human remains available for this report, the number of termites collected was greater on bones found during autumn, the rainy season in the Northeast of Brazil. The human bones examined showed termites like insects with lots of strength at bone degradation, capable of continuing the process of decomposition of human remains even in completely skeletonized bodies.

  1. Association between Sleep Duration, Insomnia Symptoms and Bone Mineral Density in Older Boston Puerto Rican Adults.

    Directory of Open Access Journals (Sweden)

    Jinya Niu

    Full Text Available To examine the association between sleep patterns (sleep duration and insomnia symptoms and total and regional bone mineral density (BMD among older Boston Puerto Rican adults.We conducted a cross-sectional study including 750 Puerto Rican adults, aged 47-79 y living in Massachusetts. BMD at 3 hip sites and the lumbar spine were measured using dual-energy X-ray absorptiometry. Sleep duration (≤5 h, 6 h, 7 h, 8 h, or ≥9 h/d and insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early-morning awaking, and non-restorative sleep were assessed by a questionnaire. Multivariable regression was used to examine sex-specific associations between sleep duration, insomnia symptoms and BMD adjusting for standard confounders and covariates.Men who slept ≥9h/d had significantly lower femoral neck BMD, relative to those reporting 8 h/d sleep, after adjusting for age, education level, smoking, physical activity, depressive symptomatology, comorbidity and serum vitamin D concentration. This association was attenuated and lost significance after further adjustment for urinary cortisol and serum inflammation biomarkers. In contrast, the association between sleep duration and BMD was not significant in women. Further, we did not find any significant associations between insomnia symptoms and BMD in men or women.Our study does not support the hypothesis that shorter sleep duration and insomnia symptoms are associated with lower BMD levels in older adults. However, our results should be interpreted with caution. Future studies with larger sample size, objective assessment of sleep pattern, and prospective design are needed before a conclusion regarding sleep and BMD can be reached.

  2. Human Bone Matrix Changes During Deep Saturation Dives

    Science.gov (United States)

    2008-08-08

    agreement notwithstanding, much remains unknown about its pathogenesis, prevention, and treatment . DON is currently disqualifying for U.S. Navy divers...recourse for symptomatic treatment is surgical joint replacement.7 The principal mechanism of bone injury is generally accepted to be bubble formation...urine concentrations of Ntx have been demonstrated in bone diseases such as osteoporosis, primary hyperthyroidism , and Paget’s disease. Also

  3. Influence of bone volume fraction and architecture on computed large-deformation failure mechanisms in human trabecular bone.

    Science.gov (United States)

    Bevill, Grant; Eswaran, Senthil K; Gupta, Atul; Papadopoulos, Panayiotis; Keaveny, Tony M

    2006-12-01

    Large-deformation bending and buckling have long been proposed as failure mechanisms by which the strength of trabecular bone can be affected disproportionately to changes in bone density, and thus may represent an important aspect of bone quality. We sought here to quantify the contribution of large-deformation failure mechanisms on strength, to determine the dependence of these effects on bone volume fraction and architecture, and to confirm that the inclusion of large-deformation effects in high-resolution finite element models improves predictions of strength versus experiment. Micro-CT-based finite element models having uniform hard tissue material properties were created from 54 cores of human trabecular bone taken from four anatomic sites (age = 70+/-11; 24 male, 27 female donors), which were subsequently biomechanically tested to failure. Strength predictions were made from the models first including, then excluding, large-deformation failure mechanisms, both for compressive and tensile load cases. As expected, strength predictions versus experimental data for the large-deformation finite element models were significantly improved (p deformation models in both tension and compression. Below a volume fraction of about 0.20, large-deformation failure mechanisms decreased trabecular strength from 5-80% for compressive loading, while effects were negligible above this volume fraction. Step-wise nonlinear multiple regression revealed that structure model index (SMI) and volume fraction (BV/TV) were significant predictors of these reductions in strength (R2 = 0.83, p deformation failure mechanisms on trabecular bone strength is highly heterogeneous and is not well explained by standard architectural metrics.

  4. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

  5. Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Minieri, Valentina; Saviozzi, Silvia; Gambarotta, Giovanna; Lo Iacono, Marco; Accomasso, Lisa; Cibrario Rocchietti, Elisa; Gallina, Clara; Turinetto, Valentina; Giachino, Claudia

    2015-04-01

    Human mesenchymal stem cells (hMSCs) are adult multipotent stem cells located in various tissues, including the bone marrow. In contrast to terminally differentiated somatic cells, adult stem cells must persist and function throughout life to ensure tissue homeostasis and repair. For this reason, they must be equipped with DNA damage responses able to maintain genomic integrity while ensuring their lifelong persistence. Evaluation of hMSC response to genotoxic insults is of great interest considering both their therapeutic potential and their physiological functions. This study aimed to investigate the response of human bone marrow MSCs to the genotoxic agent Actinomycin D (ActD), a well-known anti-tumour drug. We report that hMSCs react by undergoing premature senescence driven by a persistent DNA damage response activation, as hallmarked by inhibition of DNA synthesis, p21 and p16 protein expression, marked Senescent Associated β-galactosidase activity and enlarged γH2AX foci co-localizing with 53BP1 protein. Senescent hMSCs overexpress several senescence-associated secretory phenotype (SASP) genes and promote motility of lung tumour and osteosarcoma cell lines in vitro. Our findings disclose a multifaceted consequence of ActD treatment on hMSCs that on the one hand helps to preserve this stem cell pool and prevents damaged cells from undergoing neoplastic transformation, and on the other hand alters their functional effects on the surrounding tissue microenvironment in a way that might worsen their tumour-promoting behaviour.

  6. Impact of chronic nicotine administration on bone mineral content in young and adult rats: a comparative study.

    Science.gov (United States)

    Farag, Mahmoud M; Selima, Eman A; Salama, Mona A

    2013-11-15

    The aim of this study was to evaluate the effects of chronic nicotine administration on bone mineral homeostasis in rapidly growing young rats in comparison to effects in adult male rats. Two doses of nicotine (3 and 4.5mg/kg/day, as nicotine hydrogen tartrate) were used and rat treatment was continued for 6 months. In this study, all nicotine-treated rats weighed less than control rats and the effect was dose-dependent. Also, rats treated with nicotine had lower femoral wet weight and showed a significant reduction in femoral mid-shaft cortical width and femoral and lumbar vertebral ash weights. These effects were associated with a significant reduction of ash calcium and phosphorus contents of the femora and lumbar vertebrae. The bone mineral-lowering effects of nicotine were more severe in the lumbar vertebral spongy bone than in the femoral compact bone and these changes were more marked in adult rats than in young rats. An additional interesting observation was that the femora of young rats treated with nicotine were significantly shorter than those of control young rats. Also, the values of the femoral ash weight per unit length were significantly decreased in nicotine-treated adult rats but not in nicotine-treated young rats. Thus, these results show that nicotine-induced changes in bone vary with age. The clinical relevance of this study is that it may provide justification to insist that all people in general and the risky young group in particular should be warned against the hazards of the negative effects of nicotine on bone.

  7. Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I.; Astrakas, Loukas; Metafratzi, Zafiria; Efremidis, Stavros C. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios N. [University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece); Chalissos, Nikolaos [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece)

    2007-12-15

    Thirty-seven patients with {beta}-thalassemia major, including 14 adolescents (15.2 {+-} 3.0 years) and 23 adults (26.4 {+-} 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 {+-} 15 ms) than in adults (45.3 {+-} 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 {+-} 10.3 ms) than in adults (54.4 {+-} 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62, P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. (orig.)

  8. Living with cracks: Damage and repair in human bone

    Science.gov (United States)

    Taylor, David; Hazenberg, Jan G.; Lee, T. Clive

    2007-04-01

    Our bones are full of cracks, which form and grow as a result of daily loading activities. Bone is the major structural material in our bodies. Although weaker than many engineering materials, it has one trick that keeps it ahead - it can repair itself. Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. This article reviews the work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner. This is truly an interdisciplinary research field, requiring the close cooperation of materials scientists, biologists and engineers.

  9. Oogenesis in adult mammals, including humans: a review.

    Science.gov (United States)

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Wimalasena, Jay; Ayala, Maria E; Dominguez, Roberto

    2005-04-01

    The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries

  10. Impact of Growth Hormone on Adult Bone Quality in Turner Syndrome: A HR-pQCT Study.

    Science.gov (United States)

    Nour, Munier A; Burt, Lauren A; Perry, Rebecca J; Stephure, David K; Hanley, David A; Boyd, Steven K

    2016-01-01

    Women with Turner syndrome (TS) are known to be at risk of osteoporosis. While childhood growth hormone (GH) treatment is common in TS, the impact of this therapy on bone health has been poorly understood. The objective of this study was to determine the influence of childhood GH treatment on adult bone quality in women with TS. 28 women aged 17-45 with confirmed TS (12 GH-treated) agreed to participate in this cross-sectional study. Dual X-ray absorptiometry (DXA) of lumbar spine, hip, and radius and high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia were used to determine standard morphological and micro-architectural parameters of bone health. Finite element (FE) analysis and polar moment of inertia (pMOI) were used to estimate bone strength. GH-treated subjects were +7.4 cm taller (95% CI 2.5-12.3 cm, p = 0.005). DXA-determined areal BMD of hip, spine, and radius was similar between treatment groups. Both tibial and radial total bone areas were greater among GH-treated subjects (+20.4 and +21.2% respectively, p < 0.05), while other micro-architectural results were not different between groups. pMOI was significantly greater among GH-treated subjects (radius +35.0%, tibia +34.0%, p < 0.05). Childhood GH treatment compared to no treatment in TS was associated with an increased height, larger bones, and greater pMOI, while no significant difference in DXA-derived BMD, HR-pQCT micro-architectural parameters, or FE-estimated bone strength was detected. The higher pMOI and greater bone size may confer benefit for fracture reduction in these GH-treated patients.

  11. Undifferentiated Human Adipose-derived Stromal/Stem Cells loaded onto Wet-Spun Starch-polycaprolactone Scaffolds Enhance Bone Regeneration: Nude Mice Calvarial Defect in vivo Study

    Science.gov (United States)

    Carvalho, Pedro P.; Leonor, Isabel B.; Smith, Brenda J.; Dias, Isabel R.; Reis, Rui L.; Gimble, Jeffrey M.; Gomes, Manuela E.

    2014-01-01

    The repair of large bony defects remains challenging in the clinical setting. Human adipose-derived stromal/stem cells (hASCs) have been reported to differentiate along different cell lineages, including the osteogenic. The objective of the present study was to assess the bone regeneration potential of undifferentiated hASCs loaded in starch-polycaprolactone (SPCL) scaffolds, in a critical-sized nude mice calvarial defect. Human ASCs were isolated from lipoaspirate of five female donors, cryopreserved and pooled together. Critical-sized (4 mm) calvarial defects were created in the parietal bone of adult male nude mice. Defects were either left empty, treated with an SPCL scaffold alone, or SPCL scaffold with human ASCs. Histological analysis and Micro-CT imaging of the retrieved implants were performed. Improved new bone deposition and osseointegration was observed in SPCL loaded with hASC engrafted calvarial defects as compared to control groups that showed little healing. Non differentiated human ASCs enhance ossification of non-healing nude mice calvarial defects, and wet-spun SPCL confirmed its suitability for bone tissue engineering. This study supports the potential translation for ASC use in the treatment of human skeletal defects. PMID:24123913

  12. Human parvovirus PARV4 DNA in tissues from adult individuals: a comparison with human parvovirus B19 (B19V

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    Rotellini Matteo

    2010-10-01

    Full Text Available Abstract Background PARV4 is a new member of the Parvoviridae family not closely related to any of the known human parvoviruses. Viremia seems to be a hallmark of PARV4 infection and viral DNA persistence has been demonstrated in a few tissues. Till now, PARV4 has not been associated with any disease and its prevalence in human population has not been clearly established. This study was aimed to assess the tissue distribution and the ability to persist of PARV4 in comparison to parvovirus B19 (B19V. Results PARV4 and B19V DNA detection was carried out in various tissues of individuals without suspect of acute viral infection, by a real time PCR and a nested PCR, targeting the ORF2 and the ORF1 respectively. Low amount of PARV4 DNA was found frequently (>40% in heart and liver of adults individuals, less frequently in lungs and kidneys (23,5 and 18% respectively and was rare in bone marrow, skin and synovium samples (5,5%, 4% and 5%, respectively. By comparison, B19V DNA sequences were present in the same tissues with a higher frequency (significantly higher in myocardium, skin and bone marrow except than in liver where the frequency was the same of PARV4 DNA and in plasma samples where B19V frequency was significantly lower than that of PARV4 Conclusions The particular tropism of PARV4 for liver and heart, here emerged, suggests to focus further studies on these tissues as possible target for viral replication and on the possible role of PARV4 infection in liver and heart diseases. Neither bone marrow nor kidney seem to be a common target of viral replication.

  13. Trabecular bone histomorphometry in humans with Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Armas, Laura A G; Akhter, Mohammed P; Drincic, Andjela; Recker, Robert R

    2012-01-01

    Patients with Type 1 Diabetes Mellitus (DM) have markedly increased risk of fracture, but little is known about abnormalities in bone microarchitecture or remodeling properties that might give insight into the pathogenesis of skeletal fragility in these patients. We report here a case-control study comparing bone histomorphometric and micro-CT results from iliac biopsies in 18 otherwise healthy subjects with Type 1 Diabetes Mellitus with those from healthy age- and sex-matched non-diabetic control subjects. Five of the diabetics had histories of low-trauma fracture. Transilial bone biopsies were obtained after tetracycline labeling. The biopsy specimens were fixed, embedded, and scanned using a desktop μCT at 16 μm resolution. They were then sectioned and quantitative histomorphometry was performed as previously described by Recker et al. [1]. Two sections, >250 μm apart, were read from the central part of each biopsy. Overall there were no significant differences between diabetics and controls in histomorphometric or micro-CT measurements. However, fracturing diabetics had structural and dynamic trends different from nonfracturing diabetics by both methods of analysis. In conclusion, Type 1 Diabetes Mellitus does not result in abnormalities in bone histomorphometric or micro-CT variables in the absence of manifest complications from the diabetes. However, diabetics suffering fractures may have defects in their skeletal microarchitecture that may underlie the presence of excess skeletal fragility.

  14. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans

    DEFF Research Database (Denmark)

    Nissen, Anne; Christensen, Mikkel; Knop, Filip K

    2014-01-01

    -minute glucose clamps with co-infusion of GIP (4 pmol/kg/min for 15 min, followed by 2 pmol/kg/min for 45 min) or placebo. The samples were analyzed for concentrations of degradation products of C-terminal telopeptide of type I collagen (CTX), a bone resorption marker. RESULTS regarding effects...

  15. Bone mineral measurement, experiment M078. [space flight effects on human bone composition

    Science.gov (United States)

    Rambaut, P. C.; Vogel, J. M.; Ullmann, J.; Brown, S.; Kolb, F., III

    1973-01-01

    Measurement tests revealed few deviations from baseline bone mineral measurements after 56 days in a Skylab-type environment. No mineral change was observed in the right radius. One individual, however, showed a possible mineral loss in the left os calcis and another gained mineral in the right ulna. The cause of the gain is unclear but may be attributable to the heavy exercise routines engaged in by the crewmember in question. Equipment problems were identified during the experiment and rectified.

  16. The interactions between rat-adipose-derived stromal cells, recombinant human bone morphogenetic protein-2, and beta-tricalcium phosphate play an important role in bone tissue engineering.

    Science.gov (United States)

    E, Ling-Ling; Xu, Lu-Lu; Wu, Xia; Wang, Dong-Sheng; Lv, Yan; Wang, Jia-Zhu; Liu, Hong-Chen

    2010-09-01

    Cells, scaffolds, and growth factors are the three main factors for creating a stem-cell-based tissue-engineered construct, but the interactions between three factors are not very clear. We hereby explored the interactions between rat-adipose-derived stromal cells (rASCs), recombinant human bone morphogenetic protein-2 (rhBMP-2), and beta-tricalcium phosphate (beta-TCP) to provide evidence for their application in bone tissue engineering by evaluating the protein adsorption of beta-TCP, the cell attachment, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, mineral formation, calcium content, phosphonium content, cell vitality, gene expression, and implantation in the backs of severe combined immunodeficient mice of rhBMP-2 preinducing rASCs seeded onto beta-TCP. The results showed that beta-TCP could adsorb the proteins from the media. The attachment, proliferation, and osteogenic properties of rASCs were supported by beta-TCP, as revealed using scanning electron microscopy. Compared with rASCs cultured on the culture plate, rASCs cultured on beta-TCP had significantly higher ALP activity/protein, OCN content, and mineral formation. These values for rASCs cultured on beta-TCP with rhBMP-2 increased most significantly. The rhBMP-2 significantly increased the calcium content, phosphonium content, and ALP, type I collagen, and OCN mRNA levels of rASCs cultured on beta-TCP. The methylthiazol tetrazolium method revealed that the vitality of rASCs cultured on beta-TCP with or without rhBMP-2 for 4, 7, and 28 days in vitro was insignificantly different. After 8 and 12 weeks of implantation, each group displayed increased bone formation over the 12-week period. The percentage of the new bone formed areas for beta-TCP/rhBMP-2 and beta-TCP was not significantly different. This value for rASCs/beta-TCP construct was significantly higher than that for beta-TCP group, but the maximal and robust bone formation was presented in rASCs/beta-TCP with rhBMP-2

  17. Is There a Role for an Ultrasonic Bone-Cutting Device in Adult Spinal Deformity: A Safety and Reproducibility Study

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    Pooria Hosseini

    2016-07-01

    Full Text Available Background Ultrasonic bone-cutting devices (UBC are new cutting tools and have low frequency ultrasonic blade. There is limited data on the safety and effectiveness of using ultrasonic bone-cutting devices in the treatment of adult spinal deformities (ASD. Objectives This Retrospective review of prospectively collected data was designed to determine if the use of an ultrasonic bone-cutting device is safe in the adult spinal deformity population and to compare its effectiveness in blood loss reduction by using a comparison group from a prospective multicenter database of adult spinal deformity patients. Methods Nineteen consecutive surgical ASD cases in which the UBC was used were compared with 19 propensity-matched cases from a prospective ASD database in which conventional bone cutting instruments were used. The two groups were matched based on age, ASA, and number of levels fused posteriorly. The need for blood transfusion, volume of blood transfusion if required, estimated blood loss (EBL, and total operating time were compared between the two groups. Data were analyzed using non-parametric Mann-Whitney U test and Spearman’s Correlation test (P < 0.05. Results There was no statistically significant difference in any measured parameter between the two groups. While the EBL difference between the two groups (925 mL in the study group vs. 1628 mL in the control group was not statistically significant (P = 0.142, the 703 mL difference is clinically relevant. In addition, no complications directly related to the use of the UBC were reported. Conclusions The use of an ultrasonic bone-cutting device was shown to be safe and effective in the surgical treatment of ASD. It resulted in a 43% reduction in EBL, which was clinically relevant and statistically non-significant, without the addition of any complications. We did not identify statistical differences in transfusion rates, EBL, or operative time, which may be due to our small sample size.

  18. Cell Expansion-Dependent Inflammatory and Metabolic Profile of Human Bone Marrow Mesenchymal Stem Cells

    Science.gov (United States)

    Prieto, Patricia; Fernández-Velasco, María; Fernández-Santos, María E.; Sánchez, Pedro L.; Terrón, Verónica; Martín-Sanz, Paloma; Fernández-Avilés, Francisco; Boscá, Lisardo

    2016-01-01

    Stem cell therapy has emerged as a promising new area in regenerative medicine allowing the recovery of viable tissues. Among the many sources of adult stem cells, bone marrow-derived are easy to expand in culture via plastic adherence and their multipotentiality for differentiation make them ideal for clinical applications. Interestingly, several studies have indicated that MSCs expansion in vitro may be limited mainly due to “cell aging” related to the number of cell divisions in culture. We have determined that MSCs exhibit a progressive decline across successive passages in the expression of stem cell markers, in plasticity and in the inflammatory response, presenting low immunogenicity. We have exposed human MSCs after several passages to TLRs ligands and analyzed their inflammatory response. These cells responded to pro-inflammatory stimuli (i.e., NOS-2 expression) and to anti-inflammatory cytokines (i.e., HO1 and Arg1) until two expansions, rapidly declining upon subculture. Moreover, in the first passages, MSCs were capable to release IL1β, IL6, and IL8, as well as to produce active MMPs allowing them to migrate. Interestingly enough, after two passages, anaerobic glycolysis was enhanced releasing high levels of lactate to the extracellular medium. All these results may have important implications for the safety and efficacy of MSCs-based cell therapies. PMID:27899899

  19. CELL EXPANSION-DEPENDENT INFLAMMATORY AND METABOLIC PROFILE OF HUMAN BONE MARROW MESENCHYMAL STEM CELLS

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    PATRICIA PRIETO

    2016-11-01

    Full Text Available Stem cell therapy has emerged as a promising new area in regenerative medicine allowing the recovery of viable tissues. Among the many sources of adult stem cells, bone marrow-derived are easy to expand in culture via plastic adherence and their multipotentiality for differentiation make them ideal for clinical applications. Interestingly, several studies have indicated that MSCs expansion in vitro may be limited mainly due to cell aging related to the number of cell divisions in culture. We have determined that MSCs exhibit a progressive decline across successive passages in the expression of stem cell markers, in plasticity and in the inflammatory response, presenting low immunogenicity. We have exposed human MSCs after several passages to TLRs ligands and analyzed their inflammatory response. These cells responded to pro-inflammatory stimuli (i.e., NOS-2 expression and to anti-inflammatory cytokines (i.e., HO1 and Arg1 until two expansions, rapidly declining upon subculture. Moreover, in the first passages, MSCs were capable to release IL1β, IL6 and IL8, as well as to produce active MMPs allowing them to migrate. Interestingly enough, after two passages, anaerobic glycolysis was enhanced releasing high levels of lactate to the extracellular medium. All these results may have important implications for the safety and efficacy of MSCs-based cell therapies.

  20. Ex vivo expansion and pluripotential differentiation of cryopreserved human bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    XIANG Ying; ZHENG Qiang; JIA Bing-bing; HUANG Guo-ping; Xu Yu-lin; WANG Jin-fu; PAN Zhi-jun

    2007-01-01

    This study is aimed at investigating the potentials of ex vivo expansion and pluri-differentiation of cryopreservation of adult human bone marrow mesenchymal stem cells (hMSCs) into chondrocytes, adipocytes and neurocytes. Cryopreserved hMSCs were resuscitated and cultured for 15 passages, and then induced into chondrocytes, adipocytes and neurocytes with corresponding induction medium. The induced cells were observed for morphological properties and detected for expressions of type II collagen, triglyceride or neuron-specific enolase and nestin. The result showed that the resuscitated cells could differentiate into chondrocytes after exposure to transforming growth factor β1 (TGF-β1), insulin-like growth factor I (IGF-I) and vitamin C (Vc), and uniformly changed morphologically from a spindle-like fibroblastic appearance to a polygonal shape in three weeks. The induced cells were heterochromatic to safranin O and expressed cartilage matrix-procollagenal (II) mRNA. The resuscitated cells cultured in induction medium consisting of dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin and IGF-I showed adipogenesis, and lipid vacuoles accumulation was detectable after 21 d. The resuscitated hMSCs were also induced into neurocytes and expressed nestin and neuron specific endolase (NSE) that were special surface markers associated with neural cells at different stage. This study suggested that the resuscitated hMSCs should be still a population of pluripotential cells and that it could be used for establishing an abundant hMSC reservoir for further experiment and treatment of various clinical diseases.

  1. Bone morphogenetic protein-4 enhances vascular endothelial growth factor secretion by human retinal pigment epithelial cells.

    Science.gov (United States)

    Vogt, Rhonda R; Unda, Richard; Yeh, Lee-Chuan C; Vidro, Eileen K; Lee, John C; Tsin, Andrew T

    2006-08-01

    Retinal pigment epithelial (RPE) cells secrete vascular endothelial growth factor (VEGF), a cytokine known to promote angiogenesis. Results from RNase protection assays (RPAs) show that RPE from non-diabetic human donors and from adult retinal pigment epithelium-19 (ARPE-19) cells expressed significant bone morphogenetic protein-4 (BMP-4) message. In addition, ARPE-19 cells cultured in high glucose (25 mM), compared to those in physiological glucose (5.5 mM) released significantly more BMP-4 into the conditioned media (CM). However, the effect of BMP-4 on the release of VEGF by ARPE-19 cells has not been studied. Accordingly, ARPE-19 cells were treated with BMP-4 to determine VEGF secretion. BMP-4 and VEGF levels in the CM and cell lysates were measured by enzyme-linked immunosorbent assay (ELISA). Cells treated with exogenous BMP-4 had higher VEGF in the CM and this treatment effect was dose- and time-dependent, while cell lysates had low levels of VEGF. Addition of cycloheximide (CHX) or actinomycin-D (ACT) significantly reduced VEGF secretion from cells treated with BMP-4, suggesting that the BMP-4-induced secretion of VEGF requires new RNA and protein synthesis. Our results suggest that BMP-4 may play a role in the regulation of ocular angiogenesis associated with diabetic retinopathy (DR) by stimulating VEGF release from RPE cells.

  2. Predicting low bone density in children and young adults with quadriplegic cerebral palsy.

    Science.gov (United States)

    Henderson, Richard C; Kairalla, John; Abbas, Almas; Stevenson, Richard D

    2004-06-01

    Many children and young adults with cerebral palsy (CP) have diminished bone mineral density (BMD) and a propensity to fracture with minimal trauma. The aim of this study was to identify variables which are routinely assessed as part of standard clinical care and that might be used to identify those individuals with CP who are most likely to have low BMD. One hundred and seven participants (ages 2 years 1 month to 21 years 1 month; mean age 10 years 11 months, SD 4 years 2 months) with moderate to severe spastic CP were assessed in detail. This included gathering clinical data, taking anthropometric measures of growth and nutrition, as well as dual energy X-ray absorptiometry measures of BMD. Seventeen participants were ambulatory with assistance (Gross Motor Function Classification System [GMFCS] level III), and 90 were capable of little or no ambulation even with assistance (26 GMFCS level IV and 64 GMFCS level V). Weight z score proved to be the best predictor of BMD z score. Declining BMD z scores also correlated with increasing age and greater severity of involvement. It can be predicted, with reasonable reliability, that a 10-year-old non-ambulatory child with quadriplegic CP and a 'typical' weight z score of -2 will have a BMD z score that is at best -2. Prior fractures, use of anticonvulsants, and feeding difficulties further reduce predicted BMD.

  3. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

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    Verônica Fernandes Vianna

    2013-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term “stem cell,” this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells and those that did not adhere by three days but did by six days (L-cells. Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics.

  4. Gene Expression Changes in Femoral Head Necrosis of Human Bone Tissue

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    Bernadett Balla

    2011-01-01

    Full Text Available Osteonecrosis of the femoral head (ONFH is the result of an interruption of the local circulation and the injury of vascular supply of bone. Multiple factors have been implicated in the development of the disease. However the mechanism of ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our investigation was to identify genes that are differently expressed in ONFH vs. non-ONFH human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from ONFH male patients and 8 bone tissue samples from non-ONFH men were examined. The expression differences of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time RT-PCR system. The significance test indicated marked differences in the expression of nine genes between ONFH and non-ONFH individuals. These altered genes code for collagen molecules, an extracellular matrix digesting metalloproteinase, a transcription factor, an adhesion molecule, and a growth factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via canonical TGFB pathway as well as genes coding for extracellular matrix composing collagen type molecules. The markedly altered gene expression profile observed in the ONFH of human bone tissue may provide further insight into the pathogenetic process of osteonecrotic degeneration of bone.

  5. Local origins impart conserved bone type-related differences in human osteoblast behaviour.

    Science.gov (United States)

    Shah, M; Gburcik, V; Reilly, P; Sankey, R A; Emery, R J; Clarkin, C E; Pitsillides, A A

    2015-03-04

    Osteogenic behaviour of osteoblasts from trabecular, cortical and subchondral bone were examined to determine any bone type-selective differences in samples from both osteoarthritic (OA) and osteoporotic (OP) patients. Cell growth, differentiation; alkaline phosphatase (TNAP) mRNA and activity, Runt-related transcription factor-2 (RUNX2), SP7-transcription factor (SP7), bone sialoprotein-II (BSP-II), osteocalcin/bone gamma-carboxyglutamate (BGLAP), osteoprotegerin (OPG, TNFRSF11B), receptor activator of nuclear factor-κβ ligand (RANKL, TNFSF11) mRNA levels and proangiogenic vascular endothelial growth factor-A (VEGF-A) mRNA and protein release were assessed in osteoblasts from paired humeral head samples from age-matched, human OA/OP (n = 5/4) patients. Initial outgrowth and increase in cell number were significantly faster (p origins in OA and trabecular origins in OP. We found virtually identical bone type-related differences, however, in TNFRSF11B:TNFSF11 in OA and OP, consistent with greater potential for paracrine effects on osteoclasts in trabecular osteoblasts. Subchondral osteoblasts (OA) exhibited highest VEGF-A mRNA levels and release. Our data indicate that human osteoblasts in trabecular, subchondral and cortical bone have inherent, programmed diversity, with specific bone type-related differences in growth, differentiation and pro-angiogenic potential in vitro.

  6. Age variations in the properties of human tibial trabecular bone and cartilage

    DEFF Research Database (Denmark)

    Ding, Ming

    2000-01-01

    such as osteoarthrosis and osteoporosis, and for the design, fixation and durability of total joint prosthesis. The specific aims of the present studies were: 1) to investigate normal age-related variations in the mechanical, physical/compositional, and structural properties of human tibial trabecular bone; and 2......) to investigate the age-related and osteoarthrosis-related changes in the mechanical properties of the human tibial cartilage-bone complex; and 3) to evaluate mutual associations among various properties. Normal specimens from human autopsy proximal tibiae were used for investigation of age variations...

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

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    Ji-fu LIU

    2012-04-01

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

  8. Bone health in adults treated with endocrine therapy for early breast or prostate cancer.

    Science.gov (United States)

    Van Poznak, Catherine H

    2015-01-01

    Bone is a hormonally responsive organ. Sex hormones and calcium regulating hormones, including parathyroid hormone, 1-25 dihydroxy vitamin D, and calcitonin, have effects on bone resorption and bone deposition. These hormones affect both bone quality and bone quantity. The sex hormone estrogen inhibits bone resorption, and estrogen therapy has been developed to prevent and treat osteoporosis. Androgens are an important source of estrogen through the action of the enzyme aromatase and may themselves stimulate bone formation. Hence, the sex steroids play a role in bone metabolism. Breast cancer and prostate cancer are frequently hormonally responsive and may be treated with antiestrogens or antiandrogens respectfully. In addition, chemotherapy and supportive medications may alter the patient's endocrine system. In general, the suppression of sex hormones has a predictable affect on bone health, as seen by loss of bone mineral density and increased risk of fragility fractures. The bone toxicity of cancer-directed endocrine therapy can be mitigated through screening, counseling on optimization of calcium and vitamin D intake, exercise, and other lifestyle/behavioral actions, as well as the use of medications when the fracture risk is high. Maintaining bone health in patients who are treated with endocrine therapy for breast and prostate cancer is the focus of this review.

  9. RT-PCR standardization and bone mineralization after low-level laser therapy on adult osteoblast cells

    Science.gov (United States)

    do Bomfim, Fernando R. C.; Sella, Valéria R. G.; Zanaga, Jéssica Q.; Pereira, Nayara S.; Nouailhetas, Viviane L. A.; Plapler, Hélio

    2014-03-01

    Purpose: Osteoblasts are capable to produce different compounds directly connected to bone mineralization process. This study aims to standardize the reverse transcriptase polymerase chain reaction (RT-PCR) for adult osteoblasts to observe the effect of low level laser therapy on bone mineralization. Methods: Five-millimeter long fragments obtained from the mead femoral region of male Wistar rats were assigned into group A (n=10, laser) and group B (n=10, no laser), submitted to mechanic and enzymatic digestion. After 7 days, cultures of group A were irradiated daily on a single spot with a GaInAs laser, λ=808nm, 200mW/cm2, 2J/cm2, bean diameter of 0,02mm, 5 seconds for 6 days. Group B was manipulated but received no laser irradiation. After 13 days the cells were trypsinized for 15 minute and stabilized with RNA later® for RNA extraction with Trizol®. cDNA synthesis used 10μg of RNA and M-MLV® enzyme. PCR was accomplished using the β-actin gene as a control. Another aliquot was fixed for Hematoxylin-Eosin and Von Kossa staining to visualize bone mineralization areas. Results: Under UV light we observed clearly the amplification of β-actin gene around 400bp. HE and Von Kossa staining showed osteoblast clusters, a higher number of bone cells and well defined mineralization areas in group A. Conclusion: The cell culture, RNA extraction and RT-PCR method for adult osteoblasts was effective, allowing to use these methods for bone mineralization studies. Laser improved bone mineralization and further studies are needed involving osteogenesis, calcium release mechanisms and calcium related channels.

  10. Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury.

    Science.gov (United States)

    Liebler, Janice M; Lutzko, Carolyn; Banfalvi, Agnes; Senadheera, Dinithi; Aghamohammadi, Neema; Crandall, Edward D; Borok, Zea

    2008-08-01

    We studied the capacity of adult human bone marrow-derived cells (BMDC) to incorporate into distal lung of immunodeficient mice following lung injury. Immunodeficient NOD/SCID and NOD/SCID/beta(2) microglobulin (beta(2)M)(null) mice were administered bleomycin (bleo) or saline intranasally. One, 2, 3 and 4 days after bleo or saline, human BMDC labeled with CellTracker Green CMFDA (5-chloromethylfluorescein diacetate) were infused intravenously. Retention of CMFDA(+) cells was maximal when delivered 4 days after bleo treatment. Seven days after bleo, cells from NOD/SCID mice were CMFDA(+), which increased 10- to 100-fold in NOD/SCID/beta(2)M(null) mice. Preincubation of BMDC with Diprotin A, a reversible inhibitor of CD26 peptidase activity that enhances the stromal-derived factor-1 (SDF-1/CXCL12)/CXCR4 axis, resulted in a 30% increase in the percentage of CMFDA(+) cells retained in the lung. These data indicate that human BMDC can be identified in lungs of mice following injury, albeit at low levels, and this may be modestly enhanced by manipulation of the SDF-1/CXCR4 axis. Given the overall low number of human cells detected, methods to increase homing and retention of adult BMDC, and consideration of other stem cell populations, will likely be required to facilitate engraftment in the treatment of lung injury.

  11. Research Sees Potential to Make Bone, Muscle from Human Stem Cells

    Science.gov (United States)

    ... Sees Potential to Make Bone, Muscle From Human Stem Cells Could be a major advance for regenerative medicine, scientists say To use the ... the ability to quickly coax human embryonic (pluripotent) stem cells to ... a major advance in regenerative medicine. Pluripotent means the cells can ...

  12. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    Science.gov (United States)

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes.

  13. IFITM1 increases osteogenesis through Runx2 in human alveolar-derived bone marrow stromal cells.

    Science.gov (United States)

    Kim, Beom-Su; Kim, Hyung-Jin; Kim, Jin Seong; You, Yong-Ouk; Zadeh, Homa; Shin, Hong-In; Lee, Seung-Jin; Park, Yoon-Jeong; Takata, Takashi; Pi, Sung-Hee; Lee, Jun; You, Hyung-Keun

    2012-09-01

    The exact molecular mechanisms governing the differentiation of bone marrow stromal stem/progenitor cells (BMSCs) into osteoblasts remain largely unknown. In this study, a highly expressed protein that had a high degree of homology with interferon-induced transmembrane protein 1 (IFITM1) was identified using differentially expressed gene (DEG) screening. We sought to determine whether IFITM1 influenced osteoblast differentiation. During differentiation, IFITM1 expression gradually increased from 5 to 10days and subsequently decreased at 15 days in culture. Analysis of IFITM1 protein expression in several cell lines as well as in situ studies on human tissues revealed its selective expression in bone cells and human bone. Proliferation of human alveolar-derived bone marrow stromal cells (hAD-BMSCs) was significantly inhibited by IFITM1 knockdown by using short hairpin RNA, as were bone specific markers such as alkaline phosphatase, collagen type I α 1, bone sialoprotein, osteocalcin, and osterix were decreased. Calcium accumulation also decreased following IFITM1 knockdown. Moreover, IFITM1 knockdown in hAD-BMSCs was associated with inhibition of Runx2 mRNA and protein expression. Collectively, the present data provide evidence for the role of IFITM1 in osteoblast differentiation. The exact mechanisms of IFITM1's involvement in osteoblast differentiation are still under investigation.

  14. Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

    Directory of Open Access Journals (Sweden)

    Sanna Maria

    2006-02-01

    Full Text Available Abstract Background It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC. Cells were treated with: (1 TPA, forskolin, IBMX, FGF-1 or (2 retinoic acid and 2-mercaptoethanol (BME. Treatment (1 induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1 compared with treatment (2. In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.

  15. Human maxillary sinus floor elevation as a model for bone regeneration enabling the application of one-step surgical procedures

    NARCIS (Netherlands)

    Farre-Guasch, E.; Prins, H.J.; Overman, J.R.; ten Bruggenkate, C.M.; Schulten, E.A.J.M.; Helder, M.N.; Klein-Nulend, J.

    2013-01-01

    Bone loss in the oral and maxillofacial region caused by trauma, tumors, congenital disorders, or degenerative diseases is a health care problem worldwide. To restore (reconstruct) these bone defects, human or animal bone grafts or alloplastic (synthetic) materials have been used. However, several d

  16. Editorial: Technology for higher education, adult learning and human performance

    Directory of Open Access Journals (Sweden)

    Minhong Wang

    2013-09-01

    Full Text Available This special issue is dedicated to technology-enabled approaches for improving higher education, adult learning, and human performance. Improvement of learning and human development for sustainable development has been recognized as a key strategy for individuals, institutions, and organizations to strengthen their competitive advantages. It becomes crucial to help adult learners and knowledge workers to improve their self-directed and life-long learning capabilities. Meanwhile, advances in technology have been increasingly enabling and facilitating learning and knowledge-related initiatives.. They have largely extended learning opportunities through the provision of resource-rich and learner-centered environment, computer-based learning support, and expanded social interactions and networks. Papers in this special issue are representative of ongoing research on integration of technology with learning for innovation and sustainable development in higher education institutions and organizational and community environments.

  17. A Phase 2 Trial on the Effect of Low-Dose Versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

    Science.gov (United States)

    2015-10-01

    Supplementation on Bone Mass in Adults with Neurofibromatosis 1 ( NF1 ) PRINCIPAL INVESTIGATOR: David Viskochil, MD, PhD CONTRACTING ORGANIZATION: University...versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 ( NF1 ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1...regulatory processes have taken more time than anticipated in the Statement of Work. An IND from the FDA to use high-dose vitamin D in the NF1

  18. The relationship between the mechanical anisotropy of human cortical bone tissue and its microstructure

    Science.gov (United States)

    Espinoza Orias, Alejandro A.

    Orthopedics research has made significant advances in the areas of biomechanics, bone implants and bone substitute materials. However, to date there is no definitive model to explain the structure-property relationships in bone as a material to enable better implant designs or to develop a true biomechanical analog of bone. The objective of this investigation was to establish a relationship between the elastic anisotropy of cortical bone tissue and its microstructure. Ultrasonic wave propagation was used to measure stiffness coefficients for specimens sectioned along the length of a human femur. The elastic constants were orthotropic and varied with anatomical location. Stiffness coefficients were generally largest at the midshaft and stiffness anisotropy ratios were largest at the distal and proximal ends. These tests were run on four additional human femurs to assess the influence of phenotypic variation, and in most cases, it was found that phenotypes do not exert a significant effect. Stiffness coefficients were shown to be correlated as a power law relation to apparent density, but anisotropy ratios were not. Texture analysis was performed on selected samples to measure the orientation distribution of the bone mineral crystals. Inverse pole figures showed that bone mineral crystals had a preferred crystallographic orientation, coincident with the long axis of the femur, which is its principal loading direction. The degree of preferred orientation was represented in Multiples of a Random Distribution (MRD), and correlated to the anisotropy ratios. Variation in elastic anisotropy was shown to be primarily due to the bone mineral orientation. The results found in this work can be used to incorporate anisotropy into structural analysis for bone as a material.

  19. Thermal Conductivity of Human Bone in Cryoprobe Freezing as Related to Density.

    Science.gov (United States)

    Walker, Kyle E; Baldini, Todd; Lindeque, Bennie G

    2016-12-09

    Cryoprobes create localized cell destruction through freezing. Bone is resistant to temperature flow but is susceptible to freezing necrosis at warmer temperatures than tumor cells. Few studies have determined the thermal conductivity of human bone. No studies have examined conductivity as related to density. The study goal was to examine thermal conductivity in human bone while comparing differences between cancellous and cortical bone. An additional goal was to establish a relationship between bone density and thermal conductivity. Six knee joints from 5 cadavers were obtained. The epiphyseal region was sliced in half coronally prior to inserting an argon-circulating cryoprobe directed away from the joint line. Thermistor thermometers were placed perpendicularly at measured increments, and the freezing cycle was recorded until steady-state conditions were achieved. For 2 cortical samples, the probe was placed intramedullary in metaphyseal samples and measurements were performed radially from the central axis of each sample. Conductivity was calculated using Fournier's Law and then plotted against measured density of each sample. Across samples, density of cancellous bone ranged from 0.86 to 1.38 g/mL and average thermal conductivity ranged between 0.404 and 0.55 W/mK. Comparatively, cortical bone had a density of 1.70 to 1.86 g/mL and thermal conductivity of 0.0742 to 0.109 W/mK. A strong 2-degree polynomial correlation was seen (R(2)=0.8226, P<.001). Bone is highly resistant to temperature flow. This resistance varies and inversely correlates strongly with density. This information is clinically relevant to maximize tumor ablation while minimizing morbidity through unnecessary bone loss and damage to surrounding structures. [Orthopedics. 201x; xx(x):xx-xx.].

  20. Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China.

    Science.gov (United States)

    Guo, Qinyue; Fan, Ping; Luo, Jing; Wu, Shufang; Sun, Hongzhi; He, Lan; Zhou, Bo

    2017-03-01

    Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20-30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (β-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum β-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and β-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1-L4 and BMD total hip (see Table 3). Osteocalcin and β-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and β-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.

  1. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment of a var......Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  2. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  3. Characterization of a Composite Material to Mimic Human Cranial Bone

    Science.gov (United States)

    2015-09-01

    a general population. These file formats can be sent directly to additive manufacturing machines , generically referred to as 3-D printers, to...Illustration of the SLA additive manufacturing process. The SLA machine used in this study to manufacture specimens was a Viper Si (3D Systems, Rock...architectures while possessing physical and mechanical characteristics similar to that of bone. We are utilizing additive manufacturing , more generally

  4. Targeted regeneration of bone in the osteoporotic human femur.

    Directory of Open Access Journals (Sweden)

    Kenneth E S Poole

    Full Text Available We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness.

  5. Late effects on human bone marrow after extended field radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Parmentier, C.; Morardet, N.; Tubiana, M.

    1983-09-01

    Thirty-two patients with lymphoma were treated by extended radiotherapy (RT) at a dose of 40 Gy and were studied by ferrokinetic studies and surface counting at various times following irradiation. Loss of hematopoietic activity in the irradiated areas is compensated by increased activity in the non-irradiated areas. Despite the return of peripheral blood counts to normal, the hyperactivity of the non-irradiated bone marrow persists over up to 13 years after RT, while the hematopoietic activity of the irradiated areas remains depressed and is only slightly higher than immediately after RT. The hypoactivity persisted even when the hemopoietic tissues had been subjected to the intense stimulation provoked by an aplasia caused by chemotherapy. However, a recovery was observed for dose of 20 Gy or lower. The hemopoietic activity of the irradiated bone marrow appears to be related to the volume of the marrow irradiated and is higher after a mantle + inverted Y field than after a mantle field. Bone marrow scintigraphies with /sup 59/Fe in 7 out of 9 patients studied revealed an extension of hematopoiesis into a normally dormant area of the marrow, such as the femora. In 2 patients an erythropoietic activity was observed in spleens which had received a dose of 40 Gy, and extra medullary erythropoiesis was found in approximately two-thirds of the patients.

  6. Optical detection of carotenoid antioxidants in human bone and surrounding tissue.

    Science.gov (United States)

    Ermakov, Igor V; Ermakova, Maia R; Rosenberg, Thomas D; Gellermann, Werner

    2013-11-01

    Carotenoids are known to play an important role in health and disease state of living human tissue based on their antioxidant and optical filtering functions. In this study, we show that carotenoids exist in human bone and surrounding fatty tissue both in significant and individually variable concentrations. Measurements of biopsied tissue samples with molecule-specific Raman spectroscopy and high-performance liquid chromatography reveal that all carotenoids that are known to exist in human skin are also present in human bone. This includes all carotenes, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. We propose quantitative reflection imaging as a noncontact optical method suitable for the measurement of composite carotenoid levels in bone and surrounding tissue exposed during open surgeries such as total knee arthroplasty, and as a proof of concept, demonstrate carotenoid measurements in biopsied bone samples. This will allow one to establish potential correlations between internal tissue carotenoid levels and levels in skin and to potentially use already existing optical skin carotenoid tests as surrogate marker for bone carotenoid status.

  7. T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.

    Science.gov (United States)

    Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F

    2016-09-01

    TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

  8. Effect of boundary conditions on yield properties of human femoral trabecular bone.

    Science.gov (United States)

    Panyasantisuk, J; Pahr, D H; Zysset, P K

    2016-10-01

    Trabecular bone plays an important mechanical role in bone fractures and implant stability. Homogenized nonlinear finite element (FE) analysis of whole bones can deliver improved fracture risk and implant loosening assessment. Such simulations require the knowledge of mechanical properties such as an appropriate yield behavior and criterion for trabecular bone. Identification of a complete yield surface is extremely difficult experimentally but can be achieved in silico by using micro-FE analysis on cubical trabecular volume elements. Nevertheless, the influence of the boundary conditions (BCs), which are applied to such volume elements, on the obtained yield properties remains unknown. Therefore, this study compared homogenized yield properties along 17 load cases of 126 human femoral trabecular cubic specimens computed with classical kinematic uniform BCs (KUBCs) and a new set of mixed uniform BCs, namely periodicity-compatible mixed uniform BCs (PMUBCs). In stress space, PMUBCs lead to 7-72 % lower yield stresses compared to KUBCs. The yield surfaces obtained with both KUBCs and PMUBCs demonstrate a pressure-sensitive ellipsoidal shape. A volume fraction and fabric-based quadric yield function successfully fitted the yield surfaces of both BCs with a correlation coefficient [Formula: see text]. As expected, yield strains show only a weak dependency on bone volume fraction and fabric. The role of the two BCs in homogenized FE analysis of whole bones will need to be investigated and validated with experimental results at the whole bone level in future studies.

  9. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Science.gov (United States)

    Meier, Raphael P H; Seebach, Jörg D; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H; Muller, Yannick D

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  10. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Directory of Open Access Journals (Sweden)

    Raphael P H Meier

    Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  11. Noninvasive optical measurement of bone marrow lesions: a Monte Carlo study on visible human dataset

    Science.gov (United States)

    Su, Yu; Li, Ting

    2016-03-01

    Bone marrow is both the main hematopoietic and important immune organ. Bone marrow lesions (BMLs) may cause a series of severe complications and even myeloma. The traditional diagnosis of BMLs rely on mostly bone marrow biopsy/ puncture, and sometimes MRI, X-ray, and etc., which are either invasive and dangerous, or ionizing and costly. A diagnosis technology with advantages in noninvasive, safe, real-time continuous detection, and low cost is requested. Here we reported our preliminary exploration of feasibility verification of using near-infrared spectroscopy (NIRS) in clinical diagnosis of BMLs by Monte Carlo simulation study. We simulated and visualized the light propagation in the bone marrow quantitatively with a Monte Carlo simulation software for 3D voxelized media and Visible Chinese Human data set, which faithfully represents human anatomy. The results indicate that bone marrow actually has significant effects on light propagation. According to a sequence of simulation and data analysis, the optimal source-detector separation was suggested to be narrowed down to 2.8-3.2cm, at which separation the spatial sensitivity distribution of NIRS cover the most region of bone marrow with high signal-to-noise ratio. The display of the sources and detectors were optimized as well. This study investigated the light transport in spine addressing to the BMLs detection issue and reported the feasibility of NIRS detection of BMLs noninvasively in theory. The optimized probe design of the coming NIRS-based BMLs detector is also provided.

  12. Tumour necrosis factor-alpha (TNFα stimulates the growth of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    F. Rougier

    1997-01-01

    Full Text Available This study reports that TNF-α is a potent mitogen for human bone marrow sternal cells in vitro (assessed by [3H]-thymidine incorporation into DNA and cell counts. In contrast, cytokines such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, LIF, SCF, M-CSF, G-CSF and GM-CSF had no effect. The effect of TNF-α on the growth of human bone marrow stromal cells could be of importance during inflammatory processes which take place in the marrow, for example marrow fibrosis.

  13. Doses to the red bone marrow of young people and adults from radiation of natural origin

    Energy Technology Data Exchange (ETDEWEB)

    Kendall, G M [Childhood Cancer Research Group, University of Oxford, Richards Building, Old Road Campus, Headington, Oxford OX3 7LG (United Kingdom); Fell, T P, E-mail: Gerald.Kendall@ccrg.ox.ac.uk [Health Protection Agency, CRCE, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom)

    2011-09-01

    Natural radiation sources comprise cosmic rays, terrestrial gamma rays, radionuclides in food and inhaled isotopes of radon with their decay products. These deliver doses to all organs and tissues including red bone marrow (RBM), the tissue in which leukaemia is thought to originate. In this paper we calculate the age-dependent annual RBM doses from natural radiation sources to young people and to adults at average levels of exposure in the UK. The contributions to dose are generally less complex than in the case of doses to foetuses and young children where it is necessary to take into account transfer of radionuclides across the placenta, intakes in mother's milk and changes in gut uptake in young infants. However, there is high uptake of alkaline earths and of similar elements in the developing skeleton and this significantly affects the doses from radioisotopes of these elements, not just in the teens and twenties but through into the fifth decade of life. The total equivalent dose to the RBM from all natural sources of radiation at age 15 years is calculated to be about 1200 {mu}Sv a year at average UK levels, falling to rather less than 1100 {mu}Sv per year in later life; the gentle fall from the late teens onwards reflects the diminishing effect of the high uptakes of radioisotopes of the alkaline earths and of lead in this period. About 60% of the equivalent dose is contributed by the low linear energy transfer (LET) component. Radionuclides in food make the largest contribution to equivalent doses to RBM and much the largest contribution to the absorbed dose from high LET radiation (mainly alpha particles).

  14. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P growth.

  15. On the multiscale origins of fracture resistance in human bone and its biological degradation

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Barth, Holly D.; Ritchie, Robert O.

    2012-03-09

    Akin to other mineralized tissues, human cortical bone can resist deformation and fracture due to the nature of its hierarchical structure, which spans the molecular to macroscopic length-scales. Deformation at the smallest scales, mainly through the composite action of the mineral and collagen, contributes to bone?s strength or intrinsic fracture resistance, while crack-tip shielding mechanisms active on the microstructural scale contribute to the extrinsic fracture resistance once cracking begins. The efficiency with which these structural features can resist fracture at both small and large length-scales becomes severely degraded with such factors as aging, irradiation and disease. Indeed aging and irradiation can cause changes to the cross-link profile at fibrillar length-scales as well as changes at the three orders of magnitude larger scale of the osteonal structures, both of which combine to inhibit the bone's overall resistance to the initiation and growth of cracks.

  16. In vivo measurement of mechanical properties of human long bone by using sonic sound

    Science.gov (United States)

    Hossain, M. Jayed; Rahman, M. Moshiur; Alam, Morshed

    2016-07-01

    Vibration analysis has evaluated as non-invasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, long bone geometry and mechanical properties can be obtained by vibration analysis. In vivo measurements were performed on human ulna as a simple beam model with an experimental technique and associated apparatus. The resonant frequency of the ulna was obtained by Fast Fourier Transformation (FFT) analysis of the vibration response of piezoelectric accelerometer. Both elastic modulus and speed of the sound were inferred from the resonant frequency. Measurement error in the improved experimental setup was comparable with the previous work. The in vivo determination of bone elastic response has potential value in screening programs for metabolic bone disease, early detection of osteoporosis and evaluation of skeletal effects of various therapeutic modalities.

  17. Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

    Science.gov (United States)

    Tian, Yuke; Li, Haifeng; Zhang, Dengwen; Sun, Qiang

    2017-01-01

    Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model. Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1β and IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans. PMID:28286408

  18. Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Yi Sun

    2017-01-01

    Full Text Available Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs genetically engineered with the human proenkephalin (hPPE gene to treat bone cancer pain (BCP in a rat model. Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106 were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1β and IL-6 were ameliorated, and leucine-enkephalin (L-EK secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.

  19. Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty

    Institute of Scientific and Technical Information of China (English)

    TIAN Xiao-bin; SUN Li; YANG Shu-hua; ZHANG Yu-kun; HU Ru-yin; FU De-hao

    2008-01-01

    Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2(hBMP2)gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putry on repairing bone defects. Methods Twenty four Kunming mice were randomly divided into two groups. The nanobone putty+hBMP2 plasmid was injected into the right thigh muscle pouches of the mice(experiment side). The nanobone putty+blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1(control side 1)or group 2(control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty+hBMP2 plasmid;Group B, putty+blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. Results The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level

  20. Bone-Like Hydroxyapatite Formation in Human Blood

    Science.gov (United States)

    Titov, Anatoly T.; Larionov, Peter M.; Ivanova, Alexandra S.; Zaikovskii, Vladimir I.; Chernyavskiy, Mikhail A.

    2016-01-01

    The purpose of this study was to prove the mechanism of mineralization, when hydroxyapatite (HAP) is formed in blood plasma. These observations were substantiated by in vitro simulation of HAP crystallization in the plasma of healthy adults in a controllable quasi-physiological environment (T = 37°C, pH = 7.4) and at concentrations of dissolved Ca…

  1. Strontium-90 concentration measurements in human bones and teeth in Greece.

    Science.gov (United States)

    Stamoulis, K C; Assimakopoulos, P A; Ioannides, K G; Johnson, E; Soucacos, P N

    1999-05-19

    Strontium-90 concentration was measured in human bones and teeth collected in Greece during the period 1992-1996. One hundred and five bone samples, mainly cancellous bone, and 108 samples, taken from a total of 896 individual teeth were processed. Samples were classified according to the age and sex of the donors. Samples were chemically pre-treated according to a specially devised method to enable extraction of 90Y, at equilibrium with 90Sr in the original sample. Subsequently, 90Y beta activity was measured with a gas proportional counter. Radiostrontium concentration in bone samples showed small variations with respect to age or sex, with an average value of 30 mBq 90Sr/g Ca. However, 90Sr concentration measurements in teeth demonstrated a pronounced structure, which clearly reflects contamination from the 1960s atmospheric nuclear weapons tests and the more recent Chernobyl accident. This difference is attributed to the different histological structure of skeletal bones and teeth, the later consisting mainly of compact bone. An age-dependent model for radiostrontium concentration in human bones and teeth is developed which is able to successfully reproduce the experimental data. Through a fitting process, the model also yielded calcium turnover rates for compact bone, as a function of age, as well as an estimate of radiostrontium contamination of foodstuffs in Greece for the past four decades. The results obtained in this study indicate that radiostrontium environmental contamination which resulted from the atmospheric nuclear weapons tests in the 1960s, exceed by far that caused by the Chernobyl accident.

  2. Human dental pulp stem cell is a promising autologous seed cell for bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    LI Jing-hui; LIU Da-yong; ZHANG Fang-ming; WANG Fan; ZHANG Wen-kui; ZHANG Zhen-ting

    2011-01-01

    Background The seed cell is a core problem in bone tissue engineering research.Recent research indicates that human dental pulp stem cells (hDPSCs) can differentiate into osteoblasts in vitro,which suggests that they may become a new kind of seed cells for bone tissue engineering.The aim of this study was to evaluate the osteogenic differentiation of hDPSCs in vitro and bone-like tissue formation when transplanted with three-dimensional gelatin scaffolds in vivo,and hDPSCs may become appropriate seed cells for bone tissue engineering.Methods We have utilized enzymatic digestion to obtain hDPSCs from dental pulp tissue extracted during orthodontic treatment.After culturing and expansion to three passages,the cells were seeded in 6-well plates or on three-dimensional gelatin scaffolds and cultured in osteogenic medium.After 14 days in culture,the three-dimensional gelatin scaffolds were implanted subcutaneously in nude mice for 4 weeks.In 6-well plate culture,osteogenesis was assessed by alkaline phosphatase staining,Von Kossa staining,and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the osteogenesis-specific genes type I collagen (COL l),bone sialoprotein (BSP),osteocalcin (OCN),RUNX2,and osterix (OSX).In three-dimensional gelatin scaffold culture,X-rays,hematoxylin/eosin staining,and immunohistochemical staining were used to examine bone formation.Results In vitro studies revealed that hDPSCs do possess osteogenic differentiation potential.In vivo studies revealed that hDPSCs seeded on gelatin scaffolds can form bone structures in heterotopic sites of nude mice.Conclusions These findings suggested that hDPSCs may be valuable as seed cells for bone tissue engineering.As a special stem cell source,hDPSCs may blaze a new path for bone tissue engineering.

  3. Current data with inulin-type fructans and calcium, targeting bone health in adults.

    Science.gov (United States)

    Coxam, Véronique

    2007-11-01

    In humans, there is increasing evidence that the colon can absorb nutritionally significant amounts of calcium, and this process may be susceptible to dietary manipulation by fermentable substrates, especially inulin-type fructans. Inulin-type fructans can modulate calcium absorption because they are resistant to hydrolysis by mammalian enzymes and are fermented in the large intestine to produce short-chain fatty acids, which in turn reduce luminal pH and modify calcium speciation, and hence solubility, or exert a direct effect on the mucosal transport pathway. Quite a few intervention studies showed an improvement of calcium absorption in adolescents or young adults by inulin-type fructans. In the same way, a positive effect has been reported in older women.

  4. The nutrition intervention improved adult human capital and economic productivity.

    Science.gov (United States)

    Martorell, Reynaldo; Melgar, Paul; Maluccio, John A; Stein, Aryeh D; Rivera, Juan A

    2010-02-01

    This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children.

  5. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  6. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by {sup 99m}Tc-MDP bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yang Shunfang [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China)], E-mail: yzyg@sh163.net; Dong Qianggang [Laboratory of Mol-diagnosis, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Yao Ming [Laboratory of Pathology, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Shi Meiping [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Ye Jianding [Department of Radiology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Zhao Langxiang [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Su Jianzhong; Gu Weiyong [Shanghai Thoracic Tumor Institute, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Xie Wenhui [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Wang Kankan; Du Yanzhi [State Key Laboratory of Medical Genomics, Ruijin Hospital of Shanghai Jiaotong University, Shanghai 200025 (China); Li Yao [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China); Huang Yan [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China)], E-mail: huangyan@fudan.edu.cn

    2009-04-15

    Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with {sup 99m}Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with {sup 99m}Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as

  7. Relationships of human plasma fluoride and bone fluoride to age

    Energy Technology Data Exchange (ETDEWEB)

    Parkins, F.M.; Tinanoff, N.; Moutinho, M.; Anstey, M.B.; Waziri, M.H.

    1976-04-01

    There is evidence that fluoride levels in plasma correlate with the fluoride content in bones. The authors determined whether or not fluoride in plasma and bones might correlate with age. In 41 in-patients at the University Hospital, Iowa City, 36 of whom had been residing in fluoridated communities plasma fluoride was determined in the fasting stage by the fluoride ion selective electrode. The teeth of these children were compared with those of a neighboring city where the natural fluoride content in drinking water was 0.1 ppm. For the second sampling 42 months following the beginning of the program only 10 and 11 year old children - who had been 6 and 7 years old at the beginning of the experiment - were selected. Twenty-five boys and girls in each group were compared with a similar group of children as controls. After 28 months (approximately 33 rinsing with sodium fluoride solution) the DMF index in the fluoride-treated children was 18.4% less than in the controls. In the second group among 10 and 11 year old children after 42 months with 55 rinsings the difference was 35.0%. The author acknowledged that factors other than applications of sodium fluoride may have contributed to the prevention of caries in the fluoride-treated groups.

  8. Characteristics of porous zirconia coated with hydroxyapatite as human bones

    Indian Academy of Sciences (India)

    V V Narulkar; S Prakash; K Chandra

    2007-08-01

    Since hydroxyapatite has excellent biocompatibility and bone bonding ability, porous hydroxyapatite ceramics have been intensively studied. However, porous hydroxyapatite bodies are mechanically weak and brittle, which makes shaping and implantation difficult. One way to solve this problem is to introduce a strong porous network onto which hydroxyapatite coating is applied. In this study, porous zirconia and alumina-added zirconia ceramics were prepared by ceramic slurry infiltration of expanded polystyrene bead compacts, followed by firing at 1500°C. Then slurry of hydroxyapatite–borosilicate glass mixed powder was used to coat the porous ceramics, followed by firing at 1200°C. The porous structures without the coating had high porosities of 51–69%, high pore interconnectivity, and sufficiently large pore window sizes (300–500 m). The porous ceramics had compressive strengths of 5.3∼36.8 MPa, favourably comparable to the mechanical properties of cancellous bones. In addition, porous hydroxyapatite surface was formed on the top of the composite coating, whereas a borosilicate glass layer was found on the interface. Thus, porous zirconia-based ceramics were modified with a bioactive composite coating for biomedical applications.

  9. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  10. An animal model of adult T-cell leukemia: humanized mice with HTLV-1-specific immunity.

    Science.gov (United States)

    Tezuka, Kenta; Xun, Runze; Tei, Mami; Ueno, Takaharu; Tanaka, Masakazu; Takenouchi, Norihiro; Fujisawa, Jun-ichi

    2014-01-16

    Human T-cell leukemia virus type 1 (HTLV-1) is causally associated with adult T-cell leukemia (ATL), an aggressive T-cell malignancy with a poor prognosis. To elucidate ATL pathogenesis in vivo, a variety of animal models have been established; however, the mechanisms driving this disorder remain poorly understood due to deficiencies in each of these animal models. Here, we report a novel HTLV-1-infected humanized mouse model generated by intra-bone marrow injection of human CD133(+) stem cells into NOD/Shi-scid/IL-2Rγc null (NOG) mice (IBMI-huNOG mice). Upon infection, the number of CD4(+) human T cells in the periphery increased rapidly, and atypical lymphocytes with lobulated nuclei resembling ATL-specific flower cells were observed 4 to 5 months after infection. Proliferation was seen in both CD25(-) and CD25(+) CD4 T cells with identical proviral integration sites; however, a limited number of CD25(+)-infected T-cell clones eventually dominated, indicating an association between clonal selection of infected T cells and expression of CD25. Additionally, HTLV-1-specific adaptive immune responses were induced in infected mice and might be involved in the control of HTLV-1-infected cells. Thus, the HTLV-1-infected IBMI-huNOG mouse model successfully recapitulated the development of ATL and may serve as an important tool for investigating in vivo mechanisms of ATL leukemogenesis and evaluating anti-ATL drug and vaccine candidates.

  11. Wrapped omentum with periosteum concurrent with adipose derived adult stem cells for bone tissue engineering in dog model.

    Science.gov (United States)

    Sadegh, Amin Bigham; Basiri, Ehsan; Oryan, Ahmad; Mirshokraei, Pezhman

    2014-03-01

    Adipose derived adult stem cells (ASCs) are multipotent cells that are able to differentiate into osteoblasts in presence of certain factors. The histological characteristics of periosteum makes it a specific tissue with a unique capacity to be engineered. Higher flexibility of the greater omentum is useful for reconstructive surgery. These criteria make it suitable for tissue engineering. The present study was designed to evaluate bone tissue engineering with periosteal free graft concurrent with ASCs and pedicle omentum in dog model. Twelve young female indigenous dogs were used in this experiment. In omental group (n = 4), end of omentum was wrapped by periosteum of the radial bone in abdomen of each dog. In omental-autogenously ASCs group (n = 4), 1 ml of ASCs was injected into the wrapped omentum with periosteum while in omental-allogenously ASCs group (n = 4), 1 ml of allogenous ASCs was injected. Lateral view radiographs were taken from the abdominal cavity postoperatively at the 2nd, 4th, 6th and 8th weeks post-surgery. Eight weeks after operation the dogs were re-anesthetized and the wrapped omenum by periosteum in all groups was found and removed for histopathological evaluation. Our results showed that omentum-periosteum, omental-periosteum-autogenous ASCs and omental-periosteum-allogenous ASCs groups demonstrated bone tissue formation in the abdominal cavity in dog model. The radiological, macroscopical and histological findings of the present study by the end of 8 weeks post-surgery indicate bone tissue engineering in all three groups in an equal level. The present study has shown that the wrapped omentum with periosteum concurrent with ASCs (autogenous or allogenous ASCs) lead to a favorable bone tissue formation. We suggested that it may be useful when pedicle graft omentum used concurrent with periosteum in the bone defect reconstruction, and this phenomenon should be studied in future.

  12. Comparison of mesenchymal stem cells from human placenta and bone marrow

    Institute of Scientific and Technical Information of China (English)

    张毅; 李长东; 江小霞; 李荷莲; 唐佩弦; 毛宁

    2004-01-01

    Background Nowadays bone marrow represents the main source of mesenchymal stem cells (MSCs). We identified a new population of MSCs derived from human placenta and compared its biological characterization with bone marrow derived MSCs.Methods Mononucleated cells (MNC) were isolated from the human placenta tissue perfusate by density gradient fractionation. Individual colonies were selected and cultured in tissue dishes. At the same time, human bone marrow derived MSCs were identified. Culture-expanded cells were characterized by immune phenotyping and cultured under conditions promoting differetiation to osteoblasts or adipocytes. The hematopoietic cytokines were assayed using reverse transcriptase polymerase chain reaction (RT-PCR). Results Human placental MSCs exhibited fibroblastoid morphology. Flow cytometric analyses showed that the placental MSC were CD29, CD44, CD73, CD105, CD166, HLA-ABC positive; but were negative for CD34, CD45, and HLA-DR. Functionally, they could be induced into adipocytes or osteocytes. Moreover, several hematopoietic cytokine mRNA was found in placenta-derived MSCs by RT-PCR analysis, including IL-6, M-CSF, Flt3-ligand and SCF. These results were consistent with the properties of bone marrow derived MSCs.Conclusion These observations implicate the postpartum human placenta as an important and novel source of multipotent stem cells that could potentially be used for investigating mesenchymal differentiation and regulation of hematopoiesis.

  13. Fe and Cu stable isotopes in archeological human bones and their relationship to sex.

    Science.gov (United States)

    Jaouen, Klervia; Balter, Vincent; Herrscher, Estelle; Lamboux, Aline; Telouk, Philippe; Albarède, Francis

    2012-07-01

    Accurate sex assignment of ancient human remains usually relies on the availability of coxal bones or well-preserved DNA. Iron (Fe) and copper (Cu) stable isotope compositions ((56)Fe/(54)Fe and (65)Cu/(63)Cu, respectively) were recently measured in modern human blood, and an unexpected result was the discovery of a (56)Fe-depletion and a (65)Cu-enrichment in men's blood compared to women's blood. Bones, being pervasively irrigated by blood, are expected to retain the (56)Fe/(54)Fe and (65)Cu/(63)Cu signature of blood, which in turn is useful for determining the sex of ancient bones. Here, we report the (56)Fe/(54)Fe, (65)Cu/(63)Cu, and (66)Zn/(64)Zn ratios from a suite of well-preserved phalanxes (n = 43) belonging to individuals buried in the 17th and 18th centuries at the necropolis of Saint-Laurent de Grenoble, France, and for which the sex was independently estimated from pelvic bone morphology. The metals were purified from the bone matrix by liquid chromatography on ion exchange resin and the isotope compositions were measured by multiple-collector inductively coupled plasma mass spectrometry. The results show that, as expected from literature data on blood, male bone iron is depleted in (56)Fe and enriched in (65)Cu relative to female. No sex difference is found in the (66)Zn/(64)Zn ratios of bone. The concentration and isotopic data show no evidence of soil contamination. Four samples of five (77%) can be assigned their correct sex, a result comparable to sex assignment using Fe and Cu isotopes in blood (81%). Isotopic analysis of metals may therefore represent a valid method of sex assignment applicable to incomplete human remains.

  14. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Melanie Werner-Klein

    Full Text Available Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null (NSG and HLA-I expressing NSG mice (NSG-HLA-A2/HHD comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  15. Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

    Science.gov (United States)

    Qi, Xin; Liu, Yang; Ding, Zhen-Yu; Cao, Jia-Qing; Huang, Jing-Huan; Zhang, Jie-Yuan; Jia, Wei-Tao; Wang, Jing; Liu, Chang-Sheng; Li, Xiao-Lin

    2017-02-01

    In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration.

  16. The water jet as a new tool for endoprosthesis revision surgery--an in vitro study on human bone and bone cement.

    Science.gov (United States)

    Honl, Matthias; Rentzsch, Reemt; Schwieger, Karsten; Carrero, Volker; Dierk, Oliver; Dries, Sebastian; Louis, Hartmut; Pude, Frank; Bishop, Nick; Hille, Ekkehard; Morlock, Michael

    2003-01-01

    In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis.

  17. Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

    Science.gov (United States)

    Qi, Xin; Liu, Yang; Ding, Zhen-yu; Cao, Jia-qing; Huang, Jing-huan; Zhang, Jie-yuan; Jia, Wei-tao; Wang, Jing; Liu, Chang-sheng; Li, Xiao-lin

    2017-01-01

    In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration. PMID:28230059

  18. Low-trauma fractures and bone mineral density testing in adults with and without intellectual and developmental disabilities: a population study.

    Science.gov (United States)

    Balogh, R; Wood, J; Dobranowski, K; Lin, E; Wilton, A; Jaglal, S B; Gemmill, M; Lunsky, Y

    2017-02-01

    Individuals with intellectual and developmental disabilities (IDD) are at risk for low-trauma fractures. We investigated the rate of low-trauma fractures and the odds of BMD testing in adults with/without IDD. Adults with IDD were more likely to have a low-trauma fracture, but there was no difference in bone mineral density (BMD) testing rates.

  19. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    Institute of Scientific and Technical Information of China (English)

    Donnahue; Dennie; Jean-Pierre; Louboutin; David; S; Strayer

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors

  20. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    Science.gov (United States)

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  1. Biological Characteristics of Human Bone Marrow Mesenchymal Stem Cell Cultured in Vitro

    Institute of Scientific and Technical Information of China (English)

    FA Xian'en; WANG Lixia; HOU Jianfeng; ZHANG Ruicheng; WANG Haiyong; YANG Chenyuan

    2005-01-01

    Summary: Some biological characteristics of human bone marrow mesenchymal stem cells (MSCs) cultured in vitro were observed. hMSCs were isolated from bone marrow and purified by density gradient centrifugation method, and then cultured in vitro. The proliferation and growth characteristics of hMSCs were observed in primary and passage culture. MSCs of passage 3 were examined for the purify by positive rate of CD29 and CD44 through flow cytometry. Human bone marrow MSCs showed active proliferation capacity in vitro. The purify of MSCs separated by our method was higher than 90 %. It was concluded that hMSCs have been successfully cultured and expanded effectively. It provided a foundation for further investigation and application of MSCs.

  2. Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.

    Science.gov (United States)

    Yao, Xiaomei; Carleton, Stephanie M; Kettle, Arin D; Melander, Jennifer; Phillips, Charlotte L; Wang, Yong

    2013-06-01

    Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by bone fragility and deformities. Though the oim mouse model has been the most widely studied of the OI models, it has only recently been suggested to exhibit gender-dependent differences in bone mineralization. To characterize the impact of gender on the morphometry/ultra-structure, mechanical properties, and biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month-old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated using micro-computed tomography, three-point bending, and Raman spectroscopy. Dramatic gender differences were evident in both cortical and trabecular bone morphological and geometric parameters. Male mice had inherently more bone and increased moment of inertia than genotype-matched female counterparts with corresponding increases in bone biomechanical strength. The primary influence of gender was structure/geometry in bone growth and mechanical properties, whereas the mineral/matrix composition and hydroxyproline content of bone were influenced primarily by the oim collagen mutation. This study provides evidence of the importance of gender in the evaluation and interpretation of potential therapeutic strategies when using mouse models of OI.

  3. The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.

    Science.gov (United States)

    Guerrero, Julien; Oliveira, Hugo; Catros, Sylvain; Siadous, Robin; Derkaoui, Sidi-Mohammed; Bareille, Reine; Letourneur, Didier; Amédée, Joëlle

    2015-03-01

    Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.

  4. Determinants of bone mass and bone size in a large cohort of physically active young adult men

    Directory of Open Access Journals (Sweden)

    Garrett P

    2006-02-01

    Full Text Available Abstract The determinants of bone mineral density (BMD at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA. Peripheral-quantitative computed tomography (pQCT was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159. Mean BMD at all sites was approximately one standard deviation above young normal (p

  5. CCM2 expression during prenatal development and adult human neocortex.

    Science.gov (United States)

    Tanriover, Gamze; Sozen, Berna; Gunel, Murat; Demir, Necdet

    2011-08-01

    Cerebral cavernous malformation (CCM) is one of the most common types of vascular malformations of the central nervous system, affecting nearly one in 200 people. CCM lesions are characterized by grossly dilated vascular channels lined by a single layer of endothelium. Genetic linkage analyses have mapped three CCM loci to CCM1, CCM2 and CCM3. All three causative genes have now been identified allowing new insights into CCM pathophysiology. We focused on the CCM2 protein that might take place in blood vessel formation; we report here the expression patterns of CCM2 in prenatal development and adult human neocortex by means of immunohistochemistry and Western blot analysis. CCM2 was obviously detected in vascular endothelium and neuroglial precursor cells during development and also observed in arterial endothelium, neurons, some of the glial cells in adult neocortex. The expression patterns suggest that it could be one of the arterial markers whether this is a cause or a consequence of an altered vascular identity. CCM2 might play a role during vasculogenesis and angiogenesis during human brain development. Furthermore, with this study, CCM2 have been described for the first time in developing human neocortex.

  6. Mineralization of human bone tissue under hypokinesia and physical exercise with calcium supplements

    Science.gov (United States)

    Zorbas, Yan G.; Verentsov, Grigori E.; Abratov, Nikolai I.

    It has been suggested that physical exercise and calcium supplements may be used to prevent demineralization of bone tissue under hypokinesia (diminished muscular activity). Thus, the aim of this study was to determine mineral content of bones of 12 physically healthy men aged 19-24 years under 90 days of hypokinesia and intensive physical exercise (PE) with calcium lactate (C) supplements. They were divided into experimental and control groups with 6 men in each. The experimental group of men were subjected to hypokinesia (HK) and intensive PE and took 650 mg C 6 times per day; the control group was placed under pure HK, i.e. without the use of any preventive measures. The mineral content of different bone tissues was measured with a densitometric X-ray method in milligrams of calcium per 1 mm 3 before and after exposure to HK. The level of bone density of the examined bone tissues decreased by 7-9% and 5-7% for the control and experimental groups of men, respectively. A statistical analysis revealed that the reduction of bone mineralization was significant with P human organisms, since the entire animal kingdom had been formed in an environment of high motor activity which left its imprint on the evolution, structure, function and behaviour of animals and men. The impossibility of the body tissues to retain optimum amounts of fluid and electrolytes is the dominant hypokinetic effect.

  7. How Tough is Human Cortical Bone? In-Situ Measurements on Realistically Short Cracks

    Energy Technology Data Exchange (ETDEWEB)

    Ritchie, Robert O; Koester, K. J.; Ager III, J. W.; Ritchie, R.O.

    2008-05-10

    Bone is more difficult to break than to split. Although this is well known, and many studies exist on the behavior of long cracks in bone, there is a need for data on the orientation-dependent crack-growth resistance behavior of human cortical bone which accurately assesses its toughness at appropriate size-scales. Here we use in-situ mechanical testing in the scanning electron microscope and x-ray computed tomography to examine how physiologically-pertinent short (<600 mu m) cracks propagate in both the transverse and longitudinal orientations in cortical bone, using both crack-deflection/twist mechanics and nonlinear-elastic fracture mechanics to determine crack-resistance curves. We find that after only 500 mu m of cracking, the driving force for crack propagation was more than five times higher in the transverse (breaking) direction than in the longitudinal (splitting) direction due to major crack deflections/twists principally at cement sheathes. Indeed, our results show that the true transverse toughness of cortical bone is far higher than previously reported. However, the toughness in the longitudinal orientation, where cracks tend to follow the cement lines, is quite low at these small crack sizes; it is only when cracks become several millimeters in length that bridging mechanisms can develop leading to the (larger-crack) toughnesses generally quoted for bone.

  8. In Vitro Fracture of Human Cortical Bone: Local Fracture Criteria and Toughening Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Nalla, R; Stolken, J; Kinney, J; Ritchie, R

    2004-08-18

    A micro-mechanistic understanding of bone fracture that encompasses how cracks interact with the underlying microstructure and defines their local failure mode is lacking, despite extensive research on the response of bone to a variety of factors like aging, loading, and/or disease. Micro-mechanical models for fracture incorporating such local failure criteria have been widely developed for metallic and ceramic materials systems; however, few such deliberations have been undertaken for the fracture of bone. In fact, although the fracture event in mineralized tissues such as bone is commonly believed to be locally strain controlled, until recently there has been little experimental evidence to support this widely held belief. In the present study, a series of in vitro experiments involving a double-notch bend test geometry are performed in order to shed further light on the nature of the local cracking events that precede catastrophic fracture in bone and to define their relationship to the microstructure. Specifically, crack-microstructure interactions are examined to determine the salient toughening mechanisms in human cortical bone and to characterize how these may affect the anisotropy in fracture properties. Based on preliminary micro-mechanical models of these processes, in particular crack deflection and uncracked ligament bridging, the relative importance of these toughening mechanisms is established.

  9. Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone

    Directory of Open Access Journals (Sweden)

    Natalia Lanocha-Arendarczyk

    2016-01-01

    Full Text Available The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V, chromium (Cr, and calcium (Ca and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C, cortical bone (CB, and spongy bone (SB samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i the amount of consumed beer and (ii seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone.

  10. [Diagnostics of the skeletal massiveness and human somatotype using hand bones].

    Science.gov (United States)

    Zviagin, V N; Zamiatina, A O; Galitskaia, O I

    2003-01-01

    The skeleton massiveness (SM) and the somatotype of human constitution were determined on the basis of osteometry of bones of carpal and metacarpal bones (MB) and of phalanxes. Seventy male and 13 female skeletons from the collection of the chair for anthropology, Moscow State University, were investigated. Described are the results of examinations of 8 carpal bones made according to 3 signs (length, width, and height), and of 5 metacarpal bones made according to 4 signs (length, base and head width, and base height); investigation findings of finger phalanxes (in full) are also presented. Methods of current multidimensional statistics were used within the case study, i.e. related with the key components--for SM specification and the discriminative analysis--for constitution specification. The SM determination accuracy according to type A was 40%, according to type B--80%, according to type C--37.5% and according to type D--52.9%. The classification accuracy of constitutions by carpal bones was 50.0%, by MB--46.4%, and by MB plus finger phalanxes--48.1%. It is pointed out that it was for the first time that the elaborated quantitative criteria of osteometry of hand bones could be used in the expertise practice for the purpose of personality identification by osseous remains.

  11. Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone.

    Science.gov (United States)

    Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

    2016-01-01

    The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone).

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  13. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injur y in stroke rats

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Shiwei Du; Xinguang Yu; Xiao Han; Jincai Hou; Hao Guo

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

  14. The Human Figure Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

    Science.gov (United States)

    Packman, Wendy L.; Beck, Vanessa L.; VanZutphen, Kelly H.; Long, Janet K.; Spengler, Gisele

    2003-01-01

    There is little research on the psychological impact of bone marrow transplantation (BMT) on family members. This study uses the Human Figure Drawing (HFD) to measure siblings' emotional distress toward BMT. Among the siblings, feelings of isolation, anger, depression, anxiety, and low self-esteem emerged as major themes. Findings indicate the…

  15. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

    DEFF Research Database (Denmark)

    Jafari Kermani, Abbas; Qanie, Diyako; Andersen, Thomas L

    2017-01-01

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells...

  16. 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.

  17. Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide.

    Science.gov (United States)

    Mosna, Federico; Sensebé, Luc; Krampera, Mauro

    2010-10-01

    Mesenchymal stem cells (MSCs) are adult stem cells that hold great promise in the field of regenerative medicine. They can be isolated from almost any tissue of the body and display, after expansion, very similar properties and minor differences, probably due to their microenvironment of origin. Expansion in vitro can be obtained in cytokine-free, serum-enriched media, as well as in serum-free, basic fibroblast growth factor-enriched media. A detailed immunophenotypic analysis is required to test the purity of the preparation, but no unique distinguishing marker has been described as yet. Functional assays, that is, differentiation studies in vitro, are needed to prove multilineage differentiation of expanded cells, and demonstration of pluripotency is necessary to identify most immature precursors. MSCs show powerful immunomodulative properties toward most of the cells of the immune system: this strengthens the theoretical rationale for their use also in an allogeneic setting across the major histocompatibility complex (MHC) immunological barriers. Systemic intravenous injection and local use have been tried: after systemic injection, MSCs show a high degree of chemotaxis based on pro-inflammatory cytokines, and localize at inflamed and neoplastic tissues; local regeneration has been improved using synthetic, as well as organic scaffolds. On the other hand, inadequate heterotopic in vivo differentiation and neoplastic transformation are potential risks of this form of cell therapy, even if evidence of this sort has been collected only from studies in mice, and generally after prolonged in vitro expansion. This review tries to provide a detailed technical overview of the methods used for human bone-marrow (BM)-derived and adipose-tissue (AT)-derived MSC isolation, in vitro expansion, and characterization for tissue repair. We chose to use BM-MSCs as a model to describe techniques that have been used for MSC isolation and expansion from very different sources, and

  18. Effects of ionizing radiation on proteins in demineralized, lyophilized or frozen human bone

    Energy Technology Data Exchange (ETDEWEB)

    Antebi, Uri; Mathor, Monica B., E-mail: uri@usp.br, E-mail: mathor@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Guimaraes, Rodrigo P., E-mail: clinicaguimaraes@gmail.com [Santa Casa de Sao Paulo (FCM/SCSP), Sao Paulo, SP (Brazil). Faculdade de Ciencias Medicas

    2015-07-01

    The aim is the study of the application of ionizing radiation (gamma and electron) as sterilizing agents at doses of 15 kGy, 25 kGy and 50 kGy, the demineralized bone tissue frozen and freeze-dried for use in transplants. Five human femoral diaphysis of different donors demineralized bone tissues were preserved as lyophilized or frozen at - 80 deg C. The samples were divided into non-irradiated groups (control) and irradiated by gamma rays or electron beam. The bone proteins were extracted and used to determine the concentrations of total protein, BMP 2 and 7. It was observed a decrease in total protein concentrations, and BMP 2 and 7. The decrease in total protein concentrations, as compared to respective control groups was significant in the lyophilized and frozen samples irradiated at a dose of 50 kGy gamma radiation and beam electrons with greater than 30% reduction. The significant decrease in the levels of BMP 2 and 7 were also observed in higher doses and especially by electron beam. The reductions in the concentrations of total protein and osteoinductive proteins (BMP 2 and 7), were related to the radiation dose, i.e., increase with higher doses of ionizing radiation type and the type of preservation of the bones. The largest reductions in concentrations were observed in bone irradiated by electron beam and at a dose of 50 kGy. But this type of radiation and this high dose are not usual practice for the sterilization of bone tissue. Keywords: demineralized bone tissue, ionizing radiation, Tissue Bank, BMP 2, BMP 7, bone proteins. (author)

  19. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering.

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A; Janeczek, Agnieszka A; Kontouli, Nasia; Kanczler, Janos M; Evans, Nicholas D; Oreffo, Richard Oc

    2016-08-31

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

  20. The Relationship of Age, Body Mass Index, and Individual Habit to Bone Mineral Density in Adults

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soung Ock; Lee, In Ja; Shin, Gwi Soon [Dept. of Radiologic Techology, Dongnam Health College, Suwon (Korea, Republic of)

    2008-12-15

    We studied the change of bone mineral density (BMD) by age, body mass index (BMI), coffee, carbonated drink, alcohol, smoking, and exercise in adults who checked in health center. The number of study subjects was total 268 persons (women of 136 persons and men of 132 persons). The BMD was determined in lumbar spine and femoral neck by dual energy x-ray absorptiometry. And we got some results as below : 1. In women, mean body height was , mean body weight was 155.8{+-}6.0 cm, and mean BMI was 56.8{+-}7.9 kg. In men, mean body height was 169.1{+-}6.0 cm, mean body weight was 69.0{+-}9.5 kg, and mean BMI was 24.1{+-}2.7 kg/m{sup 2}. 2. BMD decreased as age increased, and the age was the most determinant factor for BMD (p<0.01). Women's BMD decreased rapidly in the groups aged {>=}50s, while men's BMD decreased gradually with age. In addition, for both sex, lower BMD was measured in lumbar spine than in femoral neck. 3. BMD increased in high BMI, and BMD with BMI increased distinctly in the group aged 50s. But their relationship was not significant. 4. In view of the distribution by three BMD categories, women's BMD was mostly normal in the groups aged {>=}40s but the rate of osteopenia and osteoporosis was similar in the group aged 50s, and the rate of osteoporosis was the highest in the groups aged 60s and 70s. Men's BMD was mostly normal through all groups except the group aged 70s. 5. Coffee and carbonated drink were not influenced in BMD. But alcohol-drinking group showed higher BMD than non-drinking group, and alcohol was statistically significant determinant for BMD (p<0.05). Smoking and exercise were not statistically significant determinant of BMD.

  1. Ontogeny of morningness-eveningness across the adult human lifespan

    Science.gov (United States)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  2. 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.

  3. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  4. Contour changes in human alveolar bone following tooth extraction of the maxillary central incisor.

    Science.gov (United States)

    Li, Bei; Wang, Yao

    2014-12-01

    The purpose of this study was to apply cone-beam computed tomography (CBCT) to observe contour changes in human alveolar bone after tooth extraction of the maxillary central incisor and to provide original morphological evidence for aesthetic implant treatment in the maxillary anterior area. Forty patients were recruited into the study. Each patient had two CBCT scans (CBCT I and CBCT II), one taken before and one taken three months after tooth extraction of maxillary central incisor (test tooth T). A fixed anatomic reference point was used to orient the starting axial slice of the two scans. On three CBCT I axial slices, which represented the deep, middle, and shallow layers of the socket, labial and palatal alveolar bone widths of T were measured. The number of sagittal slices from the start point to the pulp centre of T was recorded. On three CBCT II axial slices, the pulp centres of extracted T were oriented according to the number of moved sagittal slices recorded in CBCT I. Labial and palatal alveolar bone widths at the oriented sites were measured. On the CBCT I axial slice which represented the middle layer of the socket, sagittal slices were reconstructed. Relevant distances of T on the sagittal slice were measured, as were the alveolar bone width and tooth length of the opposite central incisor. On the CBCT II axial slice, which represented the middle layer of the socket, relevant distances recorded in CBCT I were transferred on the sagittal slice. The height reduction of alveolar bone on labial and palatal sides was measured, as were the alveolar bone width and tooth length of the opposite central incisor at the oriented site. Intraobserver reliability assessed by intraclass correlation coefficients (ICCs) was high. Paired sample t-tests were performed. The alveolar bone width and tooth length of the opposite central incisor showed no statistical differences (P<0.05). The labial alveolar bone widths of T at the deep, middle, and shallow layers all showed

  5. Lactase gene c/t(-13910) polymorphism, calcium intake, and pQCT bone traits in Finnish adults.

    Science.gov (United States)

    Tolonen, Sanna; Laaksonen, Marika; Mikkilä, Vera; Sievänen, Harri; Mononen, Nina; Räsänen, Leena; Viikari, Jorma; Raitakari, Olli T; Kähönen, Mika; Lehtimäki, Terho J

    2011-02-01

    Genetic lactase nonpersistence may influence calcium intake and thereby bone health. We investigated in the Cardiovascular Risk in Young Finn Study whether young adults aged 31-46 years with the C/C(-13910) genotype are more susceptible to reduced bone phenotypes, low-energy fractures, and low calcium intake than subjects with other lactase genotypes. We also analyzed the gene-environment interactions on bone with calcium intake and physical activity. Peripheral quantitative computed tomography bone traits were measured from the distal and shaft sites of the radius and tibia. The total number of those subjects whose nondominant forearm was measured and the lactase genotype was defined was 1551. Information on diet, lifestyle factors, and fractures was collected with questionnaires. The mean intake of calcium was the lowest in men with the C/C(-13910) genotype (P = 0.001). Men with the T/T(-13910) genotype had ~3% higher trabecular density at the distal radius and distal tibia compared to other lactase genotypes (P = 0.03 and 0.02, respectively). In women, we found no evidence of the gene effect at the radius and tibia. No major interactions of the C/T(-13910) polymorphism with calcium intake or physical activity on bone phenotypes were found in either sex. In conclusion, the C/T(-13910) polymorphism was associated with trabecular density at the distal radius and tibia in men. These differences may be due to the differences in calcium intake between the lactase genotypes.

  6. HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

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    Hila Haskelberg

    Full Text Available BACKGROUND: There are limited data regarding the influence of human leukocyte antigen (HLA polymorphisms on reduced bone mineral density (BMD. We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC or abacavir-lamivudine (ABC-3TC in the STEAL study. METHODS: Lumbar spine and right hip BMD were measured by Dual-energy X-ray absorptiometry (DXA. HLA genotypes at the 2-digit level were classified into class I and II supertypes. Student's t-tests were used to test the association between HLA supertypes and changes in hip and spine BMD over 96 weeks for the whole cohort and stratified by randomised groups. The relationship between HLA supertypes and BMD was also assessed in the subgroup of participants that were naïve to both ABC and TDF at study entry. RESULTS: Class II supertypes were mainly associated with hip BMD change. Overall, compared to participants not carrying HLA-DQ3, participants expressing DQ3 had less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. -0.006 g/cm2, 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. -0.006 g/cm2, 95%CI 0.001 to 0.023, p = 0.041. In participants that were naïve to both ABC and TDF at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less bone loss compared with those not carrying DQ3 (hip: 0.001 vs. -0.032 g/cm2; diff 0.033; 95%CI 0.017 to 0.049; p<0.001; spine: 0.007 vs. -0.023 g/cm2; diff 0.035; 95%CI 0.014 to 0.056; p = 0.001. CONCLUSIONS: In this cohort of HIV-infected adults, there was an association between bone status and HLA supertypes, particularly HLA-DQ3. TRIAL REGISTRATION: Clinicaltrials.gov NCT00192634.

  7. Effect of phylloquinone (vitamin K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn's disease.

    Science.gov (United States)

    O'Connor, Eibhlís M; Grealy, Geraldine; McCarthy, Jane; Desmond, Alan; Craig, Orla; Shanahan, Fergus; Cashman, Kevin D

    2014-10-14

    Although epidemiological findings support a role for vitamin K status in the improvement of bone indices in adult patients with Crohn's disease (CD), this needs to be confirmed in double-blind, randomised controlled trials (RCT) with phylloquinone (vitamin K1). By conducting two RCT, the present study aimed to first establish whether supplementation with 1000 μg of phylloquinone daily near-maximally suppresses the percentage of undercarboxylated osteocalcin in serum (%ucOC; marker of vitamin K status) in adult patients with CD currently in remission as it does in healthy adults and second determine the effect of supplementation with phylloquinone at this dose for 12 months on the indices of bone turnover and bone mass. The initial dose-ranging RCT was conducted in adult patients with CD (n 10 per group) using 0 (placebo), 1000 or 2000 μg of phylloquinone daily for 2 weeks. In the main RCT, the effect of placebo v. 1000 μg vitamin K/d (both co-administered with Ca (500 mg/d) and vitamin D3 (10 μg/d)) for 12 months (n 43 per group) on the biochemical indices of bone turnover (determined by enzyme immunoassay) and bone mass (determined by dual-energy X-ray absorptiometry) were investigated. At baseline, the mean %ucOC was 47 %, and this was suppressed upon supplementation with 1000 μg of phylloquinone daily ( - 81 %; P0·1) on bone turnover markers or on the bone mass of the lumbar spine or femur, but modestly increased (Pvitamin D3) had no effect on the indices of bone health in adult CD patients with likely vitamin K insufficiency.

  8. Does physical activity in adolescence have site-specific and sex-specific benefits on young adult bone size, content, and estimated strength?

    Science.gov (United States)

    Duckham, Rachel L; Baxter-Jones, Adam D G; Johnston, James D; Vatanparast, Hassanali; Cooper, David; Kontulainen, Saija

    2014-02-01

    The long-term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSIp ) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSIc ) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z-scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSIp , p adolescence had 10% larger adjusted CoA (p adolescence seemed to persist into young adulthood, with greater ToA and SSIp in males, and greater CoA, CoC, and TrC in females.

  9. Histological study of granulocytic series in the bone marrow of adult goat (Caprus Hircus

    Directory of Open Access Journals (Sweden)

    Yahia Dahash Hamdi

    2016-09-01

    Conclusion The developmental process of granulocytopioesis series of bone marrow in goat encompasses a lineage of successive morphological alterations involves nuclear and cytoplasmic changes as well as granule transformation resulting in the production of granulocytes.

  10. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

    DEFF Research Database (Denmark)

    Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J

    2010-01-01

    Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control....... Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag...... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies...

  11. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

    2016-08-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p animal research and a step towards a humanized in vivo model for tissue engineering.

  12. From Adult Bone Marrow Cells to Other Cell Lineages:Transdifferentiation or Cells Fusion

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Recent studies have demonstrated that intravenous transplantation or local injection of bone marrow cells can induce unexpected changes of their fate. The results of these experiments showed that after transplantation or injecton, some of tissue specific somatic cells such as hepatocytes, skeleton, cardiac muscle cells and brain cells expressed the donor cell-specific genes, such as Y chromosome. There are two hypotheses that can explain this phenomenon. One is bone marrow stem cell transdifferentiation and the other is spontaneous cell fusion.

  13. Resorption of monetite granules in alveolar bone defects in human patients.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesus; Bassett, David; Barralet, Jake; Cabarcos, Enrique L

    2010-04-01

    Bone grafting is often required to restore mandibular or maxillary bone volume prior to prosthetic tooth root implantation. Preclinical animal models are often used to study the in vivo properties of new bone graft products designed for human use. Although animal studies may offer valuable data regarding bioperformance, materials do not necessarily perform the same in human patients. In this study we implanted bovine hydroxyapatite (BH), a widely used porous apatite granule, and dicalcium phosphate anhydrous (monetite) granules, bilaterally in human patients post extraction alveolar sockets. After six months, histomorphometrical analysis of the biopsies revealed that the amount of bone regenerated with monetite (59.5 +/- 13%) was significantly higher than that obtained with BH (33.1% +/- 4.9), while the amount of unresorbed graft was higher in the sockets treated with BH (37.8 +/- 6.1) than in those implanted with monetite (25.8 +/- 14.3). Resorption of calcium phosphate ceramics is discussed by applying the Hixon-Crowell dissolution model.

  14. Biochemical and physical correlates of DNA contamination in archaeological human bones and teeth excavated at Matera, Italy

    DEFF Research Database (Denmark)

    Gilbert, M. T. P.; Rudbeck, L.; Willerslev, E.

    2005-01-01

    The majority of ancient DNA studies on human specimens have utilised teeth and bone as a source of genetic material. In this study the levels of endogenous contamination (i.e. present within the sample prior to sampling for the DNA analysis) are assessed within human bone and teeth specimens...... sampled from the cemetery of Santa Lucia alle Malve, Matera, Italy. This site is of exceptional interest, because the samples have been assayed for IS measures of biochemical and physical preservation, and it is the only one identified in a study of more than 107 animal and 154 human bones from 43 sites...... across Europe, where a significant number of human bones was well preserved. The findings demonstrate several important issues: (a) although teeth are more resilient to contamination than bone, both are readily contaminated (presumably through handling or washing), and (b) once contaminated in this way...

  15. Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow

    DEFF Research Database (Denmark)

    Potocnik, A J; Brakebusch, C; Fässler, R

    2000-01-01

    Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had...... hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta1 integrin null HSCs isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for beta1 integrin expression by retroviral cre transduction...... failed to engraft irradiated recipient mice. Moreover, absence of beta1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define beta1 integrin as an essential adhesion receptor for the homing of HSCs....

  16. Human talus bones from the Middle Pleistocene site of Sima de los Huesos (Sierra de Atapuerca, Burgos, Spain).

    Science.gov (United States)

    Pablos, Adrián; Martínez, Ignacio; Lorenzo, Carlos; Gracia, Ana; Sala, Nohemi; Arsuaga, Juan Luis

    2013-07-01

    Here we present and describe comparatively 25 talus bones from the Middle Pleistocene site of the Sima de los Huesos (SH) (Sierra de Atapuerca, Burgos, Spain). These tali belong to 14 individuals (11 adult and three immature). Although variation among Middle and Late Pleistocene tali tends to be subtle, this study has identified unique morphological characteristics of the SH tali. They are vertically shorter than those of Late Pleistocene Homo sapiens, and show a shorter head and a broader lateral malleolar facet than all of the samples. Moreover, a few shared characters with Neanderthals are consistent with the hypothesis that the SH population and Neanderthals are sister groups. These shared characters are a broad lateral malleolar facet, a trochlear height intermediate between modern humans and Late Pleistocene H. sapiens, and a short middle calcaneal facet. It has been possible to propose sex assignment for the SH tali based on their size. Stature estimates based on these fossils give a mean stature of 174.4 cm for males and 161.9 cm for females, similar to that obtained based on the long bones from this same site.

  17. Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting

    Institute of Scientific and Technical Information of China (English)

    Han-Tso Lin; Shih-Hwa Chiou; Chung-Lan Kao; Yi-Ming Shyr; Chien-Jen Hsu; Yih-Wen Tarng; Larry L-T Ho; Ching-Fai Kwok; Hung-Hai Ku

    2006-01-01

    AIM: To isolate putative pancreatic stem cells (PSCs)from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well.METHODS: By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting (FACS)was used to detect the phenotypic markers of putative PSCs.RESULTS: A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin.They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29,CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 (SH2),CD81, CD105(SH3).CONCLUSION: In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.

  18. A 3D in vitro bone organ model using human progenitor cells

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    A Papadimitropoulos

    2011-05-01

    Full Text Available Three-dimensional (3D organotypic culture models based on human cells may reduce the use of complex and costly animal models, while gaining clinical relevance. This study aimed at developing a 3D osteoblastic-osteoclastic-endothelial cell co-culture system, as an in vitro model to mimic the process of bone turnover. Osteoprogenitor and endothelial lineage cells were isolated from the stromal vascular fraction (SVF of human adipose tissue, whereas CD14+ osteoclast progenitors were derived from human peripheral blood. Cells were co-cultured within 3D porous ceramic scaffolds using a perfusion-based bioreactor device, in the presence of typical osteoclastogenic factors. After 3 weeks, the scaffolds contained cells with endothelial (2.0 ±0.3%, pre/osteoclastic (14.0 ±1.4% and mesenchymal/osteoblastic (44.0 ±8.4% phenotypes, along with tartrate-resistant acid phosphatase-positive (TRAP+ osteoclastic cells in contact with deposited bone-like matrix. Supernatant analysis demonstrated sustained matrix deposition (by C-terminus procollagen-I propeptides, resorption (by N-terminus collagen-I telopeptides and phosphate levels and osteoclastic activity (by TRAP-5b only when SVF and CD14+ cells were co-cultured. Scanning electron microscopy and magnetic resonance imaging confirmed the pattern of matrix deposition and resorption. The effectiveness of Vitamin D in replacing osteoclastogenic factors indicated a functional osteoblast-osteoclast coupling in the system. The formation of human-origin bone-like tissue, blood vessels and osteoclasts upon ectopic implantation validated the functionality of the developed cell types. The 3D co-culture system and the associated non-invasive analytical tools can be used as an advanced model to capture some aspects of the functional coupling of bone-like matrix deposition and resorption and could be exploited toward the engineering of multi-functional bone substitute implants.

  19. Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

    Science.gov (United States)

    Xia, Yi

    Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in

  20. The quartic piecewise-linear criterion for the multiaxial yield behavior of human trabecular bone.

    Science.gov (United States)

    Sanyal, Arnav; Scheffelin, Joanna; Keaveny, Tony M

    2015-01-01

    Prior multiaxial strength studies on trabecular bone have either not addressed large variations in bone volume fraction and microarchitecture, or have not addressed the full range of multiaxial stress states. Addressing these limitations, we utilized micro-computed tomography (lCT) based nonlinear finite element analysis to investigate the complete 3D multiaxial failure behavior of ten specimens (5mm cube) of human trabecular bone, taken from three anatomic sites and spanning a wide range of bone volume fraction (0.09–0.36),mechanical anisotropy (range of E3/E1¼3.0–12.0), and microarchitecture. We found that most of the observed variation in multiaxial strength behavior could be accounted for by normalizing the multiaxial strength by specimen-specific values of uniaxial strength (tension,compression in the longitudinal and transverse directions). Scatter between specimens was reduced further when the normalized multiaxial strength was described in strain space.The resulting multiaxial failure envelope in this normalized-strain space had a rectangular boxlike shape for normal–normal loading and either a rhomboidal box like shape or a triangular shape for normal-shear loading, depending on the loading direction. The finite element data were well described by a single quartic yield criterion in the 6D normalized strain space combined with a piecewise linear yield criterion in two planes for normalshear loading (mean error SD: 4.660.8% for the finite element data versus the criterion).This multiaxial yield criterion in normalized-strain space can be used to describe the complete 3D multiaxial failure behavior of human trabecular bone across a wide range of bone volume fraction, mechanical anisotropy, and microarchitecture.

  1. Evaluation of facial nerve and its landmarks in adult temporal bones

    Directory of Open Access Journals (Sweden)

    Saeid Soheilipour

    2010-06-01

    Full Text Available Introduction: The aim of this study was to identify variations of different segments of facial nerve in temporal bone. Materials and Methods: In this descriptive study that conducted on drilled bones in the temporal bone center of the Al-Zahra Hospital of Isfahan University of Medical Sciences, the landmarks of facial nerve in temporal bone were identified as separate variables and their distances from outer cortex of temporal bone and Henles spine and distances between different segments of nerve were recorded. Results: In the 50 temporal bones dissected, the distance between the tip of incus short process to the cortex was 14.2±1.96 mm, the distance between the facial recess from the facial nerve to the cortex was 14.5±2.58 mm, the distance between the stylomastoid foramen to the cortex was 20.6±2.49 mm, the distance between the lateral semicircular canal to the cortex was 15.9±2.31 mm and the distance between the sigmoid sinus dome to the cortex was 14.08±2.83 mm. The mean length of tympanic and mastoid segments (2nd and 3rd segments of facial nerve were 11.35±0.68 mm and 13.28±1.11mm, respectively. Conclusion: The mean lengths of segment of facial nerve and distant of landmarks from outer cortex of temporal bone are partially similar compared to those described in the western literature and text books, but different compared to eastern researches.

  2. Site-specific, adult bone benefits attributed to loading during youth: A preliminary longitudinal analysis.

    Science.gov (United States)

    Scerpella, Tamara A; Bernardoni, Brittney; Wang, Sijian; Rathouz, Paul J; Li, Quefeng; Dowthwaite, Jodi N

    2016-04-01

    We examined site-specific bone development in relation to childhood and adolescent artistic gymnastics exposure, comparing up to 10years of prospectively acquired longitudinal data in 44 subjects, including 31 non-gymnasts (NON) and 13 gymnasts (GYM) who participated in gymnastics from pre-menarche to ≥1.9years post-menarche. Subjects underwent annual regional and whole-body DXA scans; indices of bone geometry and strength were calculated. Anthropometrics, physical activity, and maturity were assessed annually, coincident with DXA scans. Non-linear mixed effect models centered growth in bone outcomes at menarche and adjusted for menarcheal age, height, and non-bone fat-free mass to evaluate GYM-NON differences. A POST-QUIT variable assessed the withdrawal effect of quitting gymnastics. Curves for bone area, mass (BMC), and strength indices were higher in GYM than NON at both distal radius metaphysis and diaphysis (pGYM BMC (pGYM endosteal diameter (pGYM advantages in narrow neck cortical thickness and buckling ratio (both pGYM than NON (pGYM slopes increased for distal radius diaphysis parameters (p≤0.01) and for narrow neck BR (p=0.02). At the distal radius metaphysis, GYM BMC and compressive strength slopes decreased, as did slopes for lumbar spine BMC, femoral neck BMC, and narrow neck cortical thickness (p<0.02). In conclusion, advantages in bone mass, geometry, and strength at multiple skeletal sites were noted across growth and into young adulthood in girls who participated in gymnastics loading to at least 1.9years post-menarche. Following gymnastics cessation, advantages at cortical bone sites improved or stabilized, while advantages at corticocancellous sites stabilized or diminished. Additional longitudinal observation is necessary to determine whether residual loading benefits enhance lifelong skeletal strength.

  3. Engineering a human bone marrow model: a case study on ex vivo erythropoiesis.

    Science.gov (United States)

    Mantalaris, A; Keng, P; Bourne, P; Chang, A Y; Wu, J H

    1998-01-01

    Bone marrow, with its intricate, three-dimensional tissue structure facilitating cell-cell interactions, provides a microenvironment supporting the production of hundreds of billions of multilineal blood cells everyday. We have developed a three-dimensional bone marrow culture system in which marrow cells are cultured in a reactor packed with porous microspheres. The culture supports a three-dimensional growth configuration and multilineal hemopoiesis mimicking the bone marrow in vivo. We studied ex vivo human erythropoiesis using the three-dimensional culture system. The system sustained extensive erythropoiesis at low erythropoietin concentrations (0.2 U/mL), plus stem cell factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and insulin-like growth factor-I. Erythroid cell production lasted for more than 5 weeks, and the percentage of erythroid cells in the nonadherent cell population was approximately 60%. Flow cytometric analysis using cell surface markers specific for erythroid cells (CD71 and glycophorin-A) indicated that the culture produced early, intermediate, and late erythroid cells. As the culture progressed, the erythroid cell population shifted gradually toward mature cell types. When compared to the three-dimensional culture, the traditional flask cultures failed to support extensive erythropoiesis under the same conditions. This indicates that the three-dimensional bone marrow culture system provides a microenvironment conducive to erythropoiesis under more physiological conditions and is a better bone marrow model.

  4. Radiocarbon dating and compositional analysis of pre-Columbian human bones

    Science.gov (United States)

    Andrade, E.; Solís, C.; Canto, C. E.; de Lucio, O. G.; Chavez, E.; Rocha, M. F.; Villanueva, O.; Torreblanca, C. A.

    2014-08-01

    Analysis of ancient human bones found in "El Cóporo", an archaeological site in Guanajuato, Mexico; were performed using a multi techniques scheme: 14C radiocarbon dating, IBA (Ion Beam Analysis), SEM-EDS (Scanning Electron Microscope Energy Dispersive X-ray Spectroscopy). We measured the elemental composition of the bones, especially some with a superficial black pigmentation. Soil samples collected from the burial place were also analyzed. The 14C dating was performed with a new High Voltage Europe 1 MV Tandentron Accelerator Mass Spectrometer (AMS) recently installed in the IFUNAM (Instituto de Física, Universidad Nacional Autónoma de México). The radiocarbon dating allowed us to determine the date of death of the individual in a period between the year 890 and 975 AD, which is consistent with the late period of the Cóporo civilization. The element sample analysis of bones with the surface black pigmentation show higher levels of Fe, Mn and Ba compared when bone's black surface was mechanically removed. These three elements were found in soil samples from the skeleton burial place. These results indicate more likely that the bone black coloration is due to a postmortem alteration occurring in the burial environment.

  5. Prostaglandin E2 regulates macrophage colony stimulating factor secretion by human bone marrow stromal cells.

    Science.gov (United States)

    Besse, A; Trimoreau, F; Faucher, J L; Praloran, V; Denizot, Y

    1999-07-08

    Bone marrow stromal cells regulate marrow haematopoiesis by secreting growth factors such as macrophage colony stimulating factor (M-CSF) that regulates the proliferation, differentiation and several functions of cells of the mononuclear-phagocytic lineage. By using a specific ELISA we found that their constitutive secretion of M-CSF is enhanced by tumour necrosis factor-alpha (TNF-alpha). The lipid mediator prostaglandin E2 (PGE2) markedly reduces in a time- and dose-dependent manner the constitutive and TNF-alpha-induced M-CSF synthesis by bone marrow stromal cells. In contrast, other lipid mediators such as 12-HETE, 15-HETE, leukotriene B4, leukotriene C4 and lipoxin A4 have no effect. EP2/EP4 selective agonists (11-deoxy PGE1 and 1-OH PGE1) and EP2 agonist (19-OH PGE2) inhibit M-CSF synthesis by bone marrow stromal cells while an EP1/EP3 agonist (sulprostone) has no effect. Stimulation with PGE2 induces an increase of intracellular cAMP levels in bone marrow stromal cells. cAMP elevating agents (forskolin and cholera toxin) mimic the PGE2-induced inhibition of M-CSF production. In conclusion, PGE2 is a potent regulator of M-CSF production by human bone marrow stromal cells, its effects being mediated via cAMP and PGE receptor EP2/EP4 subtypes.

  6. Effect of Aging on the Toughness of Human Cortical Bone: Evaluation by R-Curves

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, J

    2004-10-08

    Age-related deterioration of the fracture properties of bone, coupled with increased life expectancy, are responsible for increasing incidence of bone fracture in the elderly, and hence, an understanding of how its fracture properties degrade with age is essential. The present study describes ex vivo fracture experiments to quantitatively assess the effect of aging on the fracture toughness properties of human cortical bone in the longitudinal direction. Because cortical bone exhibits rising crack-growth resistance with crack extension, unlike most previous studies the toughness is evaluated in terms of resistance-curve (R-curve) behavior, measured for bone taken from wide range of age groups (34-99 years). Using this approach, both the ex vivo crack-initiation and crack-growth toughness are determined and are found to deteriorate with age; the initiation toughness decreases some 40% over six decades from 40 to 100 years, while the growth toughness is effectively eliminated over the same age range. The reduction in crack-growth toughness is considered to be associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging in the wake of the crack.

  7. Diagnosis and surgical treatment of defects in the wall of the orbit of children and adults using demineralized bone allografts.

    Science.gov (United States)

    Ryabov, Alexey; Lekishvili, Mikhail

    2016-09-01

    Accuracy of diagnosis defines the quality of treatment in patients with traumatic damage to eyelet walls. In this area, complex functional and anatomical breaches are typical and require full characterization of pathological changes in bone and soft tissue structures. A new plastic material with a high degree level of demineralization called "Perfoost" can be used to treat defects in the bones of the face of children and adults. In the present study, 79 patients with fractured eyelet walls were treated between 1999 and 2006 by grafting the defect wall with demineralized bone allografts. Grafts were applied from 2 days to 18 months after trauma. Magnetic resonance computer CT was used to check the realignment of allografts every 6 months after the reconstructive operation. The post-operative period of the observation was from 6 months to 7 years after the operation. Good or satisfactory results were obtained for 97.47 % of patients.

  8. The effect of enamel matrix derivative (Emdogain®) on gene expression profiles of human primary alveolar bone cells.

    Science.gov (United States)

    Yan, X Z; Rathe, F; Gilissen, C; van der Zande, M; Veltman, J; Junker, R; Yang, F; Jansen, J A; Walboomers, X F

    2014-06-01

    Emdogain® is frequently used in regenerative periodontal treatment. Understanding its effect on gene expression of bone cells would enable new products and pathways promoting bone formation to be established. The aim of the study was to analyse the effect of Emdogain® on expression profiles of human-derived bone cells with the help of the micro-array, and subsequent validation. Bone was harvested from non-smoking patients during dental implant surgery. After outgrowth, cells were cultured until subconfluence, treated for 24 h with either Emdogain® (100 µg/ml) or control medium, and subsequently RNA was isolated and micro-array was performed. The most important genes demonstrated by micro-array data were confirmed by qPCR and ELISA tests. Emdogain tipped the balance between genes expressed for bone formation and bone resorption towards a more anabolic effect, by interaction of the PGE2 pathway and inhibition of IL-7 production. In addition the results of the present study indicate that Emdogain possibly has an effect on gene expression for extracellular matrix formation of human bone cells, in particular on bone matrix formation and on proliferation and differentiation. With the micro-array and the subsequent validation, the genes possibly involved in Emdogain action on bone cells were identified. These results can contribute to establishing new products and pathways promoting bone formation.

  9. Voxel-based approach to generate entire human metacarpal bone with microscopic architecture for finite element analysis.

    Science.gov (United States)

    Tang, C Y; Tsui, C P; Tang, Y M; Wei, L; Wong, C T; Lam, K W; Ip, W Y; Lu, W W J; Pang, M Y C

    2014-01-01

    With the development of micro-computed tomography (micro-CT) technology, it is possible to construct three-dimensional (3D) models of human bone without destruction of samples and predict mechanical behavior of bone using finite element analysis (FEA). However, due to large number of elements required for constructing the FE models of entire bone, this demands a substantial computational effort and the analysis usually needs a high level of computer. In this article, a voxel-based approach for generation of FE models of entire bone with microscopic architecture from micro-CT image data is proposed. To enable the FE analyses of entire bone to be run even on a general personal computer, grayscale intensity thresholds were adopted to reduce the amount of elements. Human metacarpal bone (MCP) bone was used as an example for demonstrating the applicability of the proposed method. The micro-CT images of the MCP bone were combined and converted into 3D array of pixels. Dual grayscale intensity threshold parameters were used to distinguish the pixels of bone tissues from those of surrounding soft tissues and improve predictive accuracy for the FE analyses with different sizes of elements. The method of selecting an appropriate value of the second grayscale intensity threshold was also suggested to minimize the area error for the reconstructed cross-sections of a FE structure. Experimental results showed that the entire FE MCP bone with microscopic architecture could be modeled and analyzed on a personal computer with reasonable accuracy.

  10. Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation.

    Science.gov (United States)

    Yasmin, Nighat; Bauer, Thomas; Modak, Madhura; Wagner, Karin; Schuster, Christopher; Köffel, Rene; Seyerl, Maria; Stöckl, Johannes; Elbe-Bürger, Adelheid; Graf, Daniel; Strobl, Herbert

    2013-11-18

    Human Langerhans cell (LC) precursors populate the epidermis early during prenatal development and thereafter undergo massive proliferation. The prototypic antiproliferative cytokine TGF-β1 is required for LC differentiation from human CD34(+) hematopoietic progenitor cells and blood monocytes in vitro. Similarly, TGF-β1 deficiency results in LC loss in vivo. However, immunohistology studies revealed that human LC niches in early prenatal epidermis and adult basal (germinal) keratinocyte layers lack detectable TGF-β1. Here we demonstrated that these LC niches express high levels of bone morphogenetic protein 7 (BMP7) and that Bmp7-deficient mice exhibit substantially diminished LC numbers, with the remaining cells appearing less dendritic. BMP7 induces LC differentiation and proliferation by activating the BMP type-I receptor ALK3 in the absence of canonical TGF-β1-ALK5 signaling. Conversely, TGF-β1-induced in vitro LC differentiation is mediated via ALK3; however, co-induction of ALK5 diminished TGF-β1-driven LC generation. Therefore, selective ALK3 signaling by BMP7 promotes high LC yields. Within epidermis, BMP7 shows an inverse expression pattern relative to TGF-β1, the latter induced in suprabasal layers and up-regulated in outer layers. We observed that TGF-β1 inhibits microbial activation of BMP7-generated LCs. Therefore, TGF-β1 in suprabasal/outer epidermal layers might inhibit LC activation, resulting in LC network maintenance.

  11. 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.

  12. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    Directory of Open Access Journals (Sweden)

    Morten Møller

    2014-01-01

    Full Text Available Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  13. Neuropeptide Y in the adult and fetal human pineal gland.

    Science.gov (United States)

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  14. Occupational factors and risk of adult bone sarcomas: a multicentric case-control study in Europe.

    Science.gov (United States)

    Merletti, Franco; Richiardi, Lorenzo; Bertoni, Franco; Ahrens, Wolfgang; Buemi, Antoine; Costa-Santos, Cristina; Eriksson, Mikael; Guénel, Pascal; Kaerlev, Linda; Jöckel, Karl-Heinz; Llopis-Gonzalez, Agustin; Merler, Enzo; Miranda, Ana; Morales-Suárez-Varela, Maria M; Olsson, Håkan; Fletcher, Tony; Olsen, Jorn

    2006-02-01

    We investigated the association between occupational factors and risk of bone sarcoma, a rare tumor with a largely unknown aetiology. A multicentric case-control study was conducted in 7 European countries in 1995-97. Ninety-six cases aged 35-69 years with a centrally reviewed diagnosis of bone sarcoma (68 chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or colon cancer (32%) controls. Subjects were interviewed to obtain information on occupational, medical and reproductive history, smoking and alcohol consumption and selected exposures including use of pesticides. Response proportions were 90% among cases and 66% among controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for selected categories of job titles and branches of industry and for use of pesticides. We found an increased OR for bone sarcoma among blacksmiths, toolmakers, machine-tool operators (OR = 2.14, 95% CI 1.08-4.26), woodworkers (OR = 2.68, 95% CI 1.36-5.29) and construction workers (OR = 1.62, 95% CI 0.92-2.87). Ever users of pesticide had an OR of 2.33 (95% CI 1.31-4.13), with similar risks for exposure to insecticides and exposure to herbicides. Neither duration of employment in any of the analyzed occupational categories nor duration of use of pesticides showed an increasing trend in the risk of bone sarcoma. ORs of bone sarcoma were 1.03 (95% CI 0.23-4.57), 3.13 (95% CI 1.26-7.76) and 1.44 (95% CI 0.43-4.85) for the first, second and third tertile of days of use of pesticides. Our study suggests that novel and previously reported (woodworking) occupational factors play a role in the aetiology of bone sarcomas.

  15. Technical note: early post-mortem changes of human bone in taphonomy with μCT.

    Science.gov (United States)

    Le Garff, Erwan; Mesli, Vadim; Delannoy, Yann; Colard, Thomas; Demondion, Xavier; Becart, Anne; Hedouin, Valéry

    2016-12-29

    Post-mortem interval (PMI) estimation is an important issue in forensic medicine, particularly for criminal purposes and legal limitation periods. The goal of the present study is to examine the evolution of the trabecular cranial vault bone after 4 weeks of conservation in a controlled environment with micro-tomography (μCT) analyses.Four bone samples were extracted from a fresh human cranial vault (a donation to science according to the French law) and conserved in an air-controlled environment. The samples were weighed and μCT scanned at a 10-μm resolution every week after death for a month. The μCT features were identical for every sample. Each set of data from the μCTs was reconstructed, registered, and analyzed in terms of the total volume, bone volume, bone surface, number of trabeculae, trabeculae thickness, and mean distance of the trabeculae. The samples were conserved in a glass box in 20 °C air with 60% humidity in a laboratory hood between each μCT acquisition. Descriptive statistics were determined. Each sample was observed and compared to itself over time.After 1 month of conservation, the mean bone volume (-1.9%), bone surface (-5.1%), and trabecular number (-12.35%) decreased, whereas the mean trabecular separation (+5.55%) and trabecular thickness (+12.7%) increased. Many variations (i.e., increases and decreases) were observed between the extraction of the sample and the end of the 4 weeks of conservation. The present observations may be explained by bone diagenesis. Previous observations have indicated that protein and lipid losses occur with bone weight and volume losses. These diagenesis effects may explain the trabecular modifications observed in the present work. We observed many bone variations with the μCT scans between the beginning and the end of the conservation that had no explanations. Additional studies, particularly studies involving statistics, need to be performed to confirm our observations and explain these results

  16. Tensile material properties of human rib cortical bone under quasi-static and dynamic failure loading and influence of the bone microstucture on failure characteristics

    CERN Document Server

    Subit, Damien; Valazquez-Ameijide, Juan; Arregui-Dalmases, Carlos; Crandall, Jeff

    2011-01-01

    Finite element models of the thorax are under development to assist vehicle safety researchers with the design of countermeasures such as advanced restrain systems. Computational models have become more refined with increasing geometrical complexity as element size decreases. These finite element models can now capture small geometrical features with an attempt to predict fracture. However, the bone material properties currently available, and in particular the rate sensitivity, have been mainly determined from compression tests or tests on long bones. There is a need for a new set of material properties for the human rib cortical bone. With this objective, a new clamping technique was developed to test small bone coupons under tensile loading. Ten coupons were harvested from the cortical shell of the sixth and seventh left ribs from three cadavers. The coupons were tested to fracture under quasi-static (target strain rate of 0.07 %/s) and dynamic loading (target strain rate of 170 %/s). Prior to testing, eac...

  17. Ex vivo expansion of Primate CD34+ Cells isolated from Bone Marrow and Human Bone Marrow Mononuclear Cells using a Novel Scaffold

    Directory of Open Access Journals (Sweden)

    Devaprasad D

    2009-01-01

    Full Text Available Bone marrow derived CD34+ cells have been in clinical application in patients with haematological malignancies. One of the major problems with this treatment is the non-availability of matched donors or the necessity of multiple transfusions depending upon the pathology. Recently evidences have been accumulating to prove the safety and efficacy of autologous CD34+ cells in diseases such as myocardial dysfunction, peripheral vascular diseases and neurological certain conditions. However there are only a few reports in the literature on ex vivo expansion of the bone marrow derived CD34+ cells. We have in two different studies proven that isolated CD34+ cells from baboon bone marrow and non-isolated BMMNCs from human bone marrow could be expanded with increase in percentage of CD34+ cells using a novel scaffold.

  18. Effect of nitrous oxide on folate coenzyme distribution and de novo synthesis of thymidylate in human bone marrow cells

    NARCIS (Netherlands)

    A.A.M. Ermens (Anton); M. Schoester (Martijn); J. Lindemans (Jan); J. Abels

    1992-01-01

    markdownabstractAbstract The effect of nitrous oxide on intracellular folate metabolism of the human bone marrow was studied in vitro. Bone marrow cells, obtained from healthy volunteers, were incubated with 5 × 10−8m-[3H]5-formyltetrahydrofolate (5-formylTHF) for 18 hr to label intracellular fola

  19. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry

    NARCIS (Netherlands)

    Terstappen, Leon W.M.M.; Johnsen, Steen; Segers-Nolten, Ine M.J.; Loken, Michael R.

    1990-01-01

    The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma

  20. Dietary intake of vitamin K in relation to bone mineral density in Korea adults: The Korea National Health and Nutrition Examination Survey (2010-2011).

    Science.gov (United States)

    Kim, Mi-Sung; Kim, Eun-Soo; Sohn, Cheong-Min

    2015-11-01

    Low vitamin K nutritional status has been associated with increased risk of fracture, however inconsistent results exist to support the role of vitamin K on bone mineral density depending on ethnic difference and gender. Our objective was to determine vitamin K intake in Korean adults, examine correlation between vitamin K intake and bone mineral density. This study analyzed raw data from the fifth Korea National Health and Nutrition Examination Survey for adults (2,785 men, 4,307 women) aged over 19 years. Cross-sectional analyses showed only positive association between vitamin K intake and femur bone mineral density in men after adjusting bone-related factors. However, women in high tertiles of vitamin K intake had a significantly higher bone mineral density both in femur and lumber as compared to women in lowest tertiles (pvitamin K intake increased in women, but this effect was not persisted after adjusting factors. The findings of this study indicate that low dietary vitamin K intake was associated with low bone mineral density in subjects. From these results we may suggest an increase in dietary vitamin K intakes for maintaining bone mineral density. (2010-02CON-21-C, 2011-02CON-06-C).

  1. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas;

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous h......MSC population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high......-content analysis and additionally for their ability to differentiate toward osteogenesis in vitro and form bone in vivo, and their migrational ability in vivo and in vitro was investigated. RESULTS: In vitro, the two cell populations exhibited similar growth rate and differentiation capacity to osteoblasts...

  2. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    Science.gov (United States)

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p < 0.001) for the unweighted metric and not the weighted metric. The members of the bacterial communities were more similar within than between decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted).

  3. Gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells

    Institute of Scientific and Technical Information of China (English)

    胡庆柳; 朴英杰; 邹飞

    2003-01-01

    Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription, and the products were labeled with α-32P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes, and then the signals were analyzed by AtlasImage analysis software Version 1.01a.Results Fifteen genes associated with cell proliferation and signal transduction were up-regulated, and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells.Conclusion The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.

  4. Functional assay, expression of growth factors and proteins modulating bone-arrangement in human osteoblasts seeded on an anorganic bovine bone biomaterial

    Directory of Open Access Journals (Sweden)

    O Trubiani

    2010-07-01

    Full Text Available The basic aspects of bone tissue engineering include chemical composition and geometry of the scaffold design, because it is very important to improve not only cell attachment and growth but especially osteodifferentiation, bone tissue formation, and vascularization. Geistlich Bio-Oss® (GBO is a xenograft consisting of deproteinized, sterilized bovine bone, chemically and physically identical to the mineral phase of human bone.In this study, we investigated the growth behaviour and the ability to form focal adhesions on the substrate, using vinculin, a cytoskeletal protein, as a marker. Moreover, the expression of bone specific proteins and growth factors such as type I collagen, osteopontin, bone sialoprotein, bone morphogenetic protein-2 (BMP-2, BMP-7 and de novo synthesis of osteocalcin in normal human osteoblasts (NHOst seeded on xenogenic GBO were evaluated. Our observations suggest that after four weeks of culture in differentiation medium, the NHOst showed a high affinity for the three dimensional biomaterial; in fact, cellular proliferation, migration and colonization were clearly evident. The osteogenic differentiation process, as demonstrated by morphological, histochemical, energy dispersive X-ray microanalysis and biochemical analysis was mostly obvious in the NHOst grown on three-dimensional inorganic bovine bone biomaterial. Functional studies displayed a clear and significant response to calcitonin when the cells were differentiated. In addition, the presence of the biomaterial improved the response, suggesting that it could drive the differentiation of these cells towards a more differentiated osteogenic phenotype. These results encourage us to consider GBO an adequate biocompatible three-dimensional biomaterial, indicating its potential use for the development of tissue-engineering techniques.

  5. Bone marrow CFU-GM and human tumor xenograft efficacy of three antitumor nucleoside analogs.

    Science.gov (United States)

    Bagley, Rebecca G; Roth, Stephanie; Kurtzberg, Leslie S; Rouleau, Cecile; Yao, Min; Crawford, Jennifer; Krumbholz, Roy; Lovett, Dennis; Schmid, Steven; Teicher, Beverly A

    2009-05-01

    Nucleoside analogs are rationally designed anticancer agents that disrupt DNA and RNA synthesis. Fludarabine and cladribine have important roles in the treatment of hematologic malignancies. Clofarabine is a next generation nucleoside analog which is under clinical investigation. The bone marrow toxicity, tumor cell cytotoxicity and human tumor xenograft activity of fludarabine, cladribine and clofarabine were compared. Mouse and human bone marrow were subjected to colony forming (CFU-GM) assays over a 5-log concentration range in culture. NCI-60 cell line screening data were compared. In vivo, a range of clofarabine doses was compared with fludarabine for efficacy in several human tumor xenografts. The IC90 concentrations for fludarabine and cladribine for mouse CFU-GM were >30 and 0.93 microM, and for human CFU-GM were 8 and 0.11 microM, giving mouse to human differentials of >3.8- and 8.5-fold. Clofarabine produced IC90s of 1.7 microM in mouse and 0.51 microM in human CFU-GM, thus a 3.3-fold differential between species. In the NCI-60 cell line screen, fludarabine and cladribine showed selective cytotoxicity toward leukemia cell lines while for clofarabine there was no apparent selectivity based upon origin of the tumor cells. In vivo, clofarabine produced a dose-dependent increase in tumor growth delay in the RL lymphoma, the RPMI-8226 multiple myeloma, and HT-29 colon carcinoma models. The PC3 prostate carcinoma was equally responsive to clofarabine and fludarabine. Bringing together bone marrow toxicity data, tumor cell line cytotoxicity data, and human tumor xenograft efficacy provides valuable information for the translation of preclinical findings to the clinic.

  6. Results of Chiari pelvic osteotomy for acetabular dysplasia in adults; Association with bone scintigraphic findings

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Nobuo; Ozono, Kenji; Sugano, Nobuhiko; Takaoka, Kunio; Ono, Hiroo (Osaka Univ. (Japan). Faculty of Medicine)

    1993-02-01

    In an attempt to determine indications of Chiari pelvic osteotomy in acetabular dysplasia, postoperative outcome of hip joint (64 joints) was examined on the basis of findings of bone scintigraphy. The subjects were 61 patients with osteoarthrosis of hip joint who underwent preoperative bone scintigraphy. The follow-up period ranged from 2 years to 9 years and 7 months with a mean of 4 years and 9 months. According to X-ray findings, 37 osteoarthrosis joints were staged as early and 27 as progressive. Preoperative bone scintigraphic findings fell into three: (I) normal or slight hot type (33 joints), (II) hot type at the weighting part (16 joints), and (III) double hot type in the weighting part and inside part (15 joints). None of the patients had severe surgical complications such as deep-seated infection, neuroparalysis and pseudojoint. According to the clinical staging for hip joint function, 7 (47%) of 64 joints were judged as poor after osteotomy, belonging to type III. Deterioration of osteoarthrosis was seen in 11 joints (41%) on X-ray films. Of these, 9 had type III. In conclusion, Chiari pelvic osteotomy should not be indicated when type III is shown on bone scintigrams. (N.K.).

  7. Catch up in bone acquisition in young adult men with late normal puberty.

    Science.gov (United States)

    Darelid, Anna; Ohlsson, Claes; Nilsson, Martin; Kindblom, Jenny M; Mellström, Dan; Lorentzon, Mattias

    2012-10-01

    The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5-year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual-energy X-ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R(2) aBMD 11.7%; BMC 4.3%), radius (R(2) aBMD 23.5%; BMC 22.3%), and lumbar spine (R(2) aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p bone size, whereas cortical and trabecular vBMD were 0.7% (p males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years.

  8. Positive Celiac Disease Serology and Reduced Bone Mineral Density in Adult Women

    Directory of Open Access Journals (Sweden)

    Donald R Duerksen

    2010-01-01

    Full Text Available BACKGROUND: Low bone density and osteoporosis have been demonstrated in celiac disease populations in Europe, South America and the United States. Serological testing with tissue transglutaminase (TTG and immunoglobulin A endomysial (EMA antibodies is highly specific for celiac disease, while antigliadin antibody (AGA testing is less specific.

  9. Bone mineral density in adult patients treated with various antiepileptic drugs

    DEFF Research Database (Denmark)

    Beniczky, Simona Alexandra; Viken, Janina; Jensen, Lars Thorbjørn;

    2012-01-01

    There is considerable evidence suggesting, that older antiepileptic drugs (AEDs) and some of the newer ones decrease bone mineral density (BMD). However, there is only limited and conflicting data concerning the effect of levetiracetam on BMD. In this cross-sectional study we analysed data from 1...

  10. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.

    Science.gov (United States)

    Bongiovanni, Marco; Tincati, Camilla

    2006-06-01

    Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.

  11. Construction and characterization of a recombinant human adenovirus vector expressing bone morphogenetic protein 2

    OpenAIRE

    Zhang, Zheng; WANG, GUOXIAN; Li, Chen; Liu, Danping

    2013-01-01

    The aim of this study was to construct and characterize a novel recombinant human adenovirus vector expressing bone morphogenetic protein 2 (BMP2) and green fluorescent protein (GFP). The BMP2 gene in the plasmid pcDNA3-BMP2 was sequenced and the restriction enzyme recognition sites were analyzed. Following mutagenesis using polymerase chain reaction (PCR), the gene sequence after the translation termination codon was removed and new restriction sites were added. The mutated BMP2 gene (BMP2+ ...

  12. Effect of Loading Rate and Orientation on the Compressive Response of Human Cortical Bone

    Science.gov (United States)

    2014-05-01

    Biomechanics 1975, 8, 27–40. 11. Ntim, M. M.; Bembey, A. K.; Ferguson, V. I.; Bushby, A. J. Hydration Effects on the Viscoelastic Properties of Collagen. MRS...Determination of Mechanical Properties of Human Femoral Cortical Bone by the Hopkinson Bar Stress Technique. Journal of Biomechanics 1990, 23 (11...Science and Technology 2011, 25 (9), 2211–2215. 18. Chen, W.; Song, B. Split Hopkinson (Kolsky) Bar; Springer : New York, 2010; pp 29–77. 19. Kulin, R

  13. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

    Science.gov (United States)

    Cassola, V. F.; de Melo Lima, V. J.; Kramer, R.; Khoury, H. J.

    2010-01-01

    Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI_AM and female RPI_AF phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

  14. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Cassola, V F; Kramer, R; Khoury, H J [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Prof. Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); De Melo Lima, V J [Department of Anatomy, Federal University of Pernambuco, Avenida Prof. Moraes Rego, 1235, CEP 50670-901, Recife (Brazil)], E-mail: rkramer@uol.com.br

    2010-01-07

    Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI{sub A}M and female RPI{sub A}F phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

  15. Ultrastructural Evidence of Exosome Secretion by Progenitor Cells in Adult Mouse Myocardium and Adult Human Cardiospheres

    Directory of Open Access Journals (Sweden)

    Lucio Barile

    2012-01-01

    Full Text Available The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34+ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an “off-the-shelf” product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  16. Bone mineral density in obese young adults%肥胖青年骨密度状况分析

    Institute of Scientific and Technical Information of China (English)

    吕明丽; 余飞; 陆思琦; 李丹; 王舰; 吕中伟

    2012-01-01

    目的 分析肥胖青年骨密度(bone mineral density,BMD)的变化.方法 60例诊断为单纯性肥胖的患者,其中男性26例,女性34例.对照组青年与肥胖青年年龄相仿(出生日期相差<6个月).所有入选对象均排除继发性肥胖与骨代谢性疾病患者.全身诸骨扇束扫描行全身及上肢、肋骨,胸椎、腰椎、骨盆、下肢和头部7个部位骨量、骨密度测定.结果 肥胖组全身的骨量、骨密度均高于志愿者组(P<0.05).肋骨、胸椎及头部这些非承重骨肥胖组的BMC要高于志愿者组,而BMD在两组之间差异没有统计学意义;上下肢、腰椎、骨盆这些承重骨的骨量及骨密度肥胖组均明显高于志愿者组(P<0.05).结论 肥胖青年承重骨骨量及骨密度与其体质量相关,在平衡体脂因素后肥胖者与对照组骨密度无显著差别.提示肥胖患者在进行体重控制的同时应加强运动来减少体质量减轻所造成的骨量流失.%Objective To evaluate the bone mineral density (BMD) in obese young adults. Methods Sixty obese adolescents (26 males and 34 females) who visited outpatient clinic for obesity were enrolled in study (obese group) and 60 age- and sex-matched normal medical students served as control group. Subjects with secondary obesity and metabolic bone disease were excluded from the study. The BMD and bone mineral contents ( BMC) were measured by dual-energy X-ray absorptiometry for whole body, at arms, ribs, thoracic spines, lumbar spines, pelvis, legs and head. Results The overall BMC and BMD of obese group was higher than those of control group (P 0.05). Both BMC and BMD in load-bearing bones (arms, lumbar spine, pelvis, legs) of obese group was higher than those of control group (P <0.05). Conclusion The BMC and BMD of load-bearing bones in obese adolescent are related to their body weight; after adjustment for lean mass, there are no differences in BMC and BMD between obese and normal young adults. The

  17. Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with hypophosphatemic rickets

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram V; Hansen, Stinus; Folkestad, Lars;

    2015-01-01

    at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age- and weight-adjusted models, HR patients had significantly higher total bone cross-sectional areas (radius 36%, tibia 20%; both p ... impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research....

  18. Analysis of OPLA scaffolds for bone engineering constructs using human jaw periosteal cells.

    Science.gov (United States)

    Alexander, Dorothea; Hoffmann, Jürgen; Munz, Adelheid; Friedrich, Björn; Geis-Gerstorfer, Jürgen; Reinert, Siegmar

    2008-03-01

    For bone regeneration constructs using human jaw periosteal cells (JPC) the extent of osteoinductive ability of different three-dimensional scaffolds is not yet established. We analyzed open-cell polylactic acid (OPLA) scaffolds for their suitability as bone engineering constructs using human JPC. Cell adhesion and spreading was visualized on the surface of scaffolds by scanning electron microscopy. JPC proliferation within OPLA scaffolds was compared with proliferation within collagen and calcium phosphate scaffolds. We found a significant increase of proliferation rates in OPLA scaffolds versus Coll/CaP scaffolds at three time points. Live-measurements of oxygen consumption within the cell-seeded scaffolds indicate that the in vitro culturing time should not exceed 12-15 days. OPLA scaffolds, which were turned out to be the most beneficial for JPC growth, were chosen for osteogenic differentiation experiments with or without BMP-2. Gene expression analyses demonstrated induction of several osteogenic genes (alkaline phosphatase, osterix, Runx-2 and insulin-like growth factor) within the 3D-scaffolds after 12 days of in vitro culturing. Element analysis by EDX spectrometry of arising nodules during osteogenesis demonstrated that JPC growing within OPLA scaffolds are able to form CaP particles. We conclude that OPLA scaffolds provide a promising environment for bone substitutes using human JPC.

  19. On the origin of human adipocytes and the contribution of bone marrow-derived cells.

    Science.gov (United States)

    Rydén, Mikael

    2016-01-01

    In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic dysfunction. Adipocytes are derived from precursors present primarily in the perivascular areas of adipose tissue but their precise origin remains unclear. The multipotent differentiation capacity of bone marrow-derived cells (BMDC) has prompted the suggestion that BMDC may contribute to different cell tissue pools, including adipocytes. However, data in murine transplantation models have been conflicting and it has been a matter of debate whether BMDC actually differentiate into adipocytes or just fuse with resident fat cells. To resolve this controversy in humans, we recently performed a study in 65 subjects that had undergone bone marrow transplantation. Using a set of newly developed assays including single cell genome-wide analyses of mature adipocytes, we demonstrated that bone marrow contributes with approximately 10 % to the adipocyte pool. This proportion was more than doubled in obesity, suggesting that BMDC may constitute a reserve pool for adipogenesis, particularly upon weight gain. This commentary discusses the possible relevance of these and other recent findings for human pathophysiology.

  20. Structural mechanical properties of radiation-sterilized human Bone-Tendon-Bone grafts preserved by different methods.

    Science.gov (United States)

    Gut, Grzegorz; Marowska, Joanna; Jastrzebska, Anna; Olender, Ewa; Kamiński, Artur

    2016-06-01

    To avoid the risk of infectious disease transmission from donor to recipient, allografts should be terminally sterilized. In the previous paper (Kaminski et al. in Cell Tissue Bank 10:215-219, 2009) we presented the effect of various methods of preservation (deep fresh freezing, glycerolization, lyophilization), followed by irradiation with different doses of electron beam (EB), on material (intrinsic) mechanical properties of human patellar tendons cut out as for anterior cruciate ligament reconstruction, obtained in failure tensile test. As structural mechanical properties are equally important to predict the behaviour of the graft as a whole functional unit, the purpose of the present paper was to show the results for failure load and elongation, obtained in the same experiment. Paired Bone-Tendon-Bone grafts (BTB) were prepared from cadaveric human patella tendons with both patellar and tibial attachments. They were preserved by deep freezing, glycerolization or lyophilization and subsequently EB-irradiated with the doses of 25, 35, 50 or 100 kGy (fresh-frozen grafts) or a single dose of 35 kGy (glycerolized and lyophilized grafts). Each experimental (irradiated) group was provided with control (non-irradiated), donor-matched group. The specimens from all groups were subjected to mechanical failure tensile test with the use of Instron system in order to measure their structural properties (failure load and elongation). All lyophilized grafts were rehydrated before mechanical testing. In our study we did not observe significant deterioration of structural mechanical properties of BTB grafts processed by fresh-freezing and then terminal sterilized with growing doses of EB up to 100 kGy. In contrast, BTB grafts processed by glycerolization or lyophilization and irradiated with 35 kGy showed significant decrease of failure load. Obtained results suggest that deep-frozen irradiated grafts retain their initial mechanical properties to an extent which does not

  1. Dropouts and Compliance in Exercise Interventions Targeting Bone Mineral Density in Adults: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    George A. Kelley

    2013-01-01

    Full Text Available Background. Dropouts and compliance to exercise interventions targeting bone mineral density (BMD in adults are not well established. The purpose of this study was to address that gap. Methods. Meta-analysis of randomized controlled exercise intervention trials in adults ≥18 years of age. The primary outcomes were dropouts in the exercise and control groups as well as compliance to the exercise interventions. A random-effects model was used to pool results. Moderator analyses were conducted using mixed-effects ANOVA-like models and metaregression. Statistical significance was set at . Results. Thirty-six studies representing 3,297 participants (1,855 exercise, 1,442 control were included. Dropout rates in the exercise and control groups averaged 20.9% (95% CI 16.7%–25.9% and 15.9% (11.8%–21.1% while compliance to exercise was 76.3% (71.7%–80.3%. For both exercise and control groups, greater dropout rates were associated with studies conducted in the USA versus other countries, females versus males, premenopausal versus postmenopausal women, younger versus older participants, longer studies (controls only, and high- versus moderate-intensity training (exercisers only. Greater compliance to exercise was associated with being female, home- or facility-based exercise versus both, and shorter studies. Conclusion. These findings provide important information for researchers and practitioners with respect to exercise programs targeting BMD in adults.

  2. Low oxygen tension stimulates redifferentiation of dedifferentiated adult human nasal chondrocytes

    NARCIS (Netherlands)

    Malda, J.; Blitterswijk, van C.A.; Geffen, van M.; Martens, D.E.; Tramper, J.; Riesle, J.

    2004-01-01

    Objective: To determine the effect of dissolved oxygen tension (DO) on the redifferentiation of dedifferentiated adult human nasal septum chondrocytes cultured as pellets. Design: After isolation, human nasal chondrocytes were expanded in monolayer culture, which resulted in their dedifferentiation.

  3. Low oxygen tension stimulates the redifferentiation of dedifferentiated adult human nasal chondrocytes

    NARCIS (Netherlands)

    Malda, J.; Blitterswijk, van C.A.; Geffen, van M.; Martens, D.E.; Tramper, J.; Riesle, J.

    2004-01-01

    Objective: To determine the effect of dissolved oxygen tension (DO) on the redifferentiation of dedifferentiated adult human nasal septum chondrocytes cultured as pellets. - Design: After isolation, human nasal chondrocytes were expanded in monolayer culture, which resulted in their dedifferentiati

  4. Comprehensive cellular-resolution atlas of the adult human brain.

    Science.gov (United States)

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  5. Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase.

    Science.gov (United States)

    Baruteau, Julien; Nyabi, Omar; Najimi, Mustapha; Fauvart, Maarten; Sokal, Etienne

    2014-09-01

    Phenylketonuria (PKU) is one of the most prevalent inherited metabolic diseases and is accountable for a severe encephalopathy by progressive intoxication of the brain by phenylalanine. This results from an ineffective L-phenylalanine hydroxylase enzyme (PAH) due to a mutated phenylalanine hydroxylase (PAH) gene. Neonatal screening programs allow an early dietetic treatment with restrictive phenylalanine intake. This diet prevents most of the neuropsychological disabilities but remains challenging for lifelong compliance. Adult-derived human liver progenitor cells (ADHLPC) are a pool of precursors that can differentiate into hepatocytes. We aim to study PAH expression and PAH activity in a differenciated ADHLPC. ADHLPC were isolated from human hepatocyte primary culture of two different donors and differenciated under specific culture conditions. We demonstrated the high expression of PAH and a large increase of PAH activity in differenciated LPC. The age of the donor, the cellular viability after liver digestion and cryopreservation affects PAH activity. ADHLPC might therefore be considered as a suitable source for cell therapy in PKU.

  6. A Study on Bone 1Mineral Density in Xiamen Adults%厦门市成年人骨密度现状的研究

    Institute of Scientific and Technical Information of China (English)

    程小游; 杨阳; 周晓东; 徐建清; 钟新生

    2014-01-01

    Aims to performed ultrasound bone mineral density measurement in Xiamen city between 20~59 years old adults, bone mineral density current understanding of adults in Xiamen City , for osteoporosis screening and pro-vide scientific basis for prevention of osteoporosis .Bone mineral density was measured by Ultrasound Bone Densi-tometer SONOST-2000.Adults osteoporosis incidence rate was 22.8%, adults bone mineral density level is low in Xiamen city, in the younger group also appeared a certain degree of osteoporosis , and male osteoporosis rate than does the female low .And male adults also appeared the phenomenon of missing bone premature .%通过对厦门市20~59岁成年人进行超声骨密度测量,了解厦门市成年人骨密度现状为骨质疏松高危人群的筛查与骨质疏松的预防提供科学依据。使用Sonost-2000超声骨密度仪测定跟骨超声参数。结果显示:厦门市成年人骨质疏松总发生率22.8%,厦门市成年人骨密度水平较低,在年轻人群中也出现了一定程度的骨质疏松现象,并且男性的骨质疏松率并不比女性低。厦门市男性成年人骨峰值出现在20~39岁,女性骨峰值出现在40~49岁,两者都存在峰值骨量偏低的情况,并且男性成年人还出现骨量过早丢失的现象。

  7. Radiocarbon dating and compositional analysis of pre-Columbian human bones

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, E., E-mail: andrade@fisica.unam.mx [Instituto de Física, Universidad Nacional Autónoma de México, Apartado Postal 20-364, 01000 México D.F. (Mexico); Solís, C.; Canto, C.E.; Lucio, O.G. de [Instituto de Física, Universidad Nacional Autónoma de México, Apartado Postal 20-364, 01000 México D.F. (Mexico); Chavez, E. [ESIME-Z, Instituto Politécnico Nacional, ALM Zacatenco, 07738 México D.F. (Mexico); Rocha, M.F.; Villanueva, O.; Torreblanca, C.A. [Centro INAH Zacatecas, Miguel Auza No. 205, Col. Centro, Zacatecas/Zacatecas CP 98000 (Mexico)

    2014-08-01

    Analysis of ancient human bones found in “El Cóporo”, an archaeological site in Guanajuato, Mexico; were performed using a multi techniques scheme: {sup 14}C radiocarbon dating, IBA (Ion Beam Analysis), SEM-EDS (Scanning Electron Microscope Energy Dispersive X-ray Spectroscopy). We measured the elemental composition of the bones, especially some with a superficial black pigmentation. Soil samples collected from the burial place were also analyzed. The {sup 14}C dating was performed with a new High Voltage Europe 1 MV Tandentron Accelerator Mass Spectrometer (AMS) recently installed in the IFUNAM (Instituto de Física, Universidad Nacional Autónoma de México). The radiocarbon dating allowed us to determine the date of death of the individual in a period between the year 890 and 975 AD, which is consistent with the late period of the Cóporo civilization. The element sample analysis of bones with the surface black pigmentation show higher levels of Fe, Mn and Ba compared when bone’s black surface was mechanically removed. These three elements were found in soil samples from the skeleton burial place. These results indicate more likely that the bone black coloration is due to a postmortem alteration occurring in the burial environment.

  8. An analysis of factors affecting the mercury content in the human femoral bone.

    Science.gov (United States)

    Zioła-Frankowska, A; Dąbrowski, M; Kubaszewski, Ł; Rogala, P; Kowalski, A; Frankowski, M

    2017-01-01

    The study was carried out to determine the content of mercury in bone tissue of the proximal femur (head and neck bone) of 95 patients undergoing total hip replacement due to osteoarthritis, using CF-AFS analytical technique. Furthermore, the investigations were aimed at assessing the impact of selected factors, such as age, gender, tobacco smoking, alcohol consumption, exposure to chemical substance at work, type of degenerative changes, clinical evaluation and radiological parameters, type of medications, on the concentration of mercury in the head and neck of the femur, resected in situ. Mercury was obtained in all samples of the head and neck of the femur (n = 190) in patients aged 25-91 years. The mean content of mercury for the whole group of patients was as follows: 37.1 ± 35.0 ng/g for the femoral neck and 24.2 ± 19.5 ng/g for the femoral head. The highest Hg contents were found in femoral neck samples, both in women and men, and they amounted to 169.6 and 176.5 ng/g, respectively. The research showed that the mercury content of bones can be associated with body mass index, differences in body anatomy, and gender. The uses of statistical analysis gave the possibility to define the influence of factors on mercury content in human femoral bones.

  9. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength.

  10. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  11. Analysis of Bone Mineral Density According to the Biochemical Variable Markers in Adults

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Geun [Dept. of Radiology, Woosuk University Hospital, Chonju (Korea, Republic of); Kweon, Dae Cheol; Song, Woon Heung [Shinheung College University, Uijungbu (Korea, Republic of)

    2009-12-15

    To evaluate the bone mineral density (BMD) and biochemical markers. We evaluated the BMD of femoral neck and lumbar spines of 998(male 568, female 430) persons who took a regular health screening in Woosuk University Hospital from September 2007 to March 2008 by dual energy bone mineral densitometry. Results of BMD are different in terms of biochemical markers. Especially aged people showed osteoporotic change progressively. Degree of osteoporosis increases with age. A steep decrease of BMD can be found in postmenopausal women who have low level of female hormone. More persistent effort is needed to find out the factors that can reduce BMD values for prevention of problems by osteoporosis. In essence, research on factors related to other biochemical markers must be studied continuously.

  12. Human ESC-Derived MSCs Outperform Bone Marrow MSCs in the Treatment of an EAE Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Xiaofang Wang

    2014-07-01

    Full Text Available Current therapies for multiple sclerosis (MS are largely palliative, not curative. Mesenchymal stem cells (MSCs harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs. Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE.

  13. Identification of a distinct small cell population from human bone marrow reveals its multipotency in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    James Wang

    Full Text Available Small stem cells, such as spore-like cells, blastomere-like stem cells (BLSCs, and very-small embryonic-like stem cells (VSELs have been described in recent studies, although their multipotency in human tissues has not yet been confirmed. Here, we report the discovery of adult multipotent stem cells derived from human bone marrow, which we call StemBios (SB cells. These isolated SB cells are smaller than 6 ìm and are DAPI+ and Lgr5+ (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5. Because Lgr5 has been characterized as a stem cell marker in the intestine, we hypothesized that SB cells may have a similar function. In vivo cell tracking assays confirmed that SB cells give rise to three types of cells, and in vitro studies demonstrated that SB cells cultured in proprietary media are able to grow to 6-25 ìm in size. Once the SB cells have attached to the wells, they differentiate into different cell lineages upon exposure to specific differentiation media. We are the first to demonstrate that stem cells smaller than 6 ìm can differentiate both in vivo and in vitro. In the future, we hope that SB cells will be used therapeutically to cure degenerative diseases.

  14. Bmp2 conditional knockout in osteoblasts and endothelial cells does not impair bone formation after injury or mechanical loading in adult mice.

    Science.gov (United States)

    McBride-Gagyi, Sarah Howe; McKenzie, Jennifer A; Buettmann, Evan G; Gardner, Michael J; Silva, Matthew J

    2015-12-01

    Post-natal osteogenesis after mechanical trauma or stimulus occurs through either endochondral healing, intramembranous healing or lamellar bone formation. Bone morphogenetic protein 2 (BMP2) is up-regulated in each of these osteogenic processes and is expressed by a variety of cells including osteoblasts and vascular cells. It is known that genetic knockout of Bmp2 in all cells or in osteo-chondroprogenitor cells completely abrogates endochondral healing after full fracture. However, the importance of BMP2 from differentiated osteoblasts and endothelial cells is not known. Moreover, the importance of BMP2 in non-endochondral bone formation such as intramembranous healing or lamellar bone formation is not known. Using inducible and tissue-specific Cre-lox mediated targeting of Bmp2 in adult (10-24 week old) mice, we assessed the role of BMP2 expression globally, by osteoblasts, and by vascular endothelial cells in endochondral healing, intramembranous healing and lamellar bone formation. These three osteogenic processes were modeled using full femur fracture, ulnar stress fracture, and ulnar non-damaging cyclic loading, respectively. Our results confirmed the requirement of BMP2 for endochondral fracture healing, as mice in which Bmp2 was knocked out in all cells prior to fracture failed to form a callus. Targeted deletion of Bmp2 in osteoblasts (osterix-expressing) or vascular endothelial cells (vascular endothelial cadherin-expressing) did not impact fracture healing in any way. Regarding non-endochondral bone formation, we found that BMP2 is largely dispensable for intramembranous bone formation after stress fracture and also not required for lamellar bone formation induced by mechanical loading. Taken together our results indicate that osteoblasts and endothelial cells are not a critical source of BMP2 in endochondral fracture healing, and that non-endochondral bone formation in the adult mouse is not as critically dependent on BMP2.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    by bioluminescence imaging (BLI). In order to identify the molecular phenotype associated with enhanced migration, we carried out comparative DNA microarray analysis of gene expression of hBMSC-derived high bone forming (HBF) clones versus low bone forming (LBF) clones. RESULTS: HBF clones were exhibited higher ex...

  16. Energy Availability and Dietary Patterns of Adult Male and Female Competitive Cyclists With Lower Than Expected Bone Mineral Density.

    Science.gov (United States)

    Viner, Rebecca T; Harris, Margaret; Berning, Jackie R; Meyer, Nanna L

    2015-12-01

    The purpose of this study was to assess energy availability (EA) and dietary patterns of 10 adult (29-49 years) male (n = 6) and female (n = 4) competitive (USA Cycling Category: Pro, n = 2; 1-4, n = 8) endurance cyclists (5 road, 5 off-road), with lower than expected bone mineral density (BMD; Z score competition (C), and off-season (OS) were estimated from 3-day dietary records, completed once per month, across a cycling season. BMD was measured by DXA at 0 months/5 months/10 months. The Three-Factor Eating Questionnaire (TFEQ) was used to assess cognitive dietary restraint. Seventy percent of participants had low EA [(LEA); competitive road and off-road cyclists in the United States may be at risk for long-term LEA. Further studies are needed to explore strategies to prevent and monitor long-term LEA in these athletes.

  17. Human Non-Hematopoietic CD271pos/CD140alow/neg Bone Marrow Stroma Cells Fulfill Stringent Stem Cell Criteria in Serial Transplantations

    Science.gov (United States)

    Ghazanfari, Roshanak; Li, Hongzhe; Zacharaki, Dimitra; Lim, Hooi Ching

    2016-01-01

    Human bone marrow contains a population of non-hematopoietic stromal stem/progenitor cells (BMSCs), which play a central role for bone marrow stroma and the hematopoietic microenvironment. However, the precise characteristics and potential stem cell properties of defined BMSC populations have not yet been thoroughly investigated. Using standard adherent colony-forming unit fibroblast (CFU-F) assays, we have previously shown that BMSCs were highly enriched in the nonhematopoietic CD271pos/CD140alow/neg fraction of normal adult human bone marrow. In this study, we demonstrate that prospectively isolated CD271pos/CD140alow/neg BMSCs expressed high levels of hematopoiesis supporting genes and signature mesenchymal and multipotency genes on a single cell basis. Furthermore, CD271pos/CD140alow/neg BMSCs gave rise to non-adherent sphere colonies (mesenspheres) with typical surface marker profile and trilineage in vitro differentiation potential. Importantly, serial transplantations of CD271pos/CD140alow/neg BMSC-derived mesenspheres (single cell and bulk) into immunodeficient NOD scid gamma (NSG) mice showed increased mesensphere numbers and full differentiation potential after both primary and secondary transplantations. In contrast, BMSC self-renewal potential decreased under standard adherent culture conditions. These data therefore indicate that CD271pos/CD140alow/neg BMSCs represent a population of primary stem cells with MSC phenotype and sphere-forming capacity that fulfill stringent functional stem cell criteria in vivo in a serial transplantation setting. PMID:27527928

  18. A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

    Science.gov (United States)

    Claros, Silvia; Rico-Llanos, Gustavo A.; Becerra, José; Andrades, José A.

    2014-01-01

    Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF (recombinant human TGF)-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein)-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo. PMID:24968268

  19. A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Silvia Claros

    2014-06-01

    Full Text Available Transforming growth factor-beta (TGF-β is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS for 10 days in the presence of rhTGF (recombinant human TGF-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo.

  20. Enhanced human bone marrow mesenchymal stem cell functions on cathodic arc plasma-treated titanium.

    Science.gov (United States)

    Zhu, Wei; Teel, George; O'Brien, Christopher M; Zhuang, Taisen; Keidar, Michael; Zhang, Lijie Grace

    2015-01-01

    Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium's osseointegration involves inducing bio-mimetic nanotopography to enhance cell-implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC) attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications.

  1. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  2. Effects of ionizing radiation on proteins in lyophilized or frozen demineralized human bone

    Science.gov (United States)

    Antebi, Uri; Mathor, Monica Beatriz; da Silva, André Ferreira; Guimarães, Rodrigo Pereira; Honda, Emerson Kiyoshi

    2016-01-01

    Objective The aim was to study the effects of application of ionizing radiation (gamma and electrons) as sterilizing agents at doses of 15 kGy, 25 kGy and 50 kGy, on lyophilized or frozen demineralized bone tissue for use in transplants. Methods Five human femoral diaphyses from different donors of musculoskeletal tissue were demineralized and preserved as lyophilized or frozen at −80 °C. The samples were divided into two groups: non-irradiated (control) and irradiated by means of gamma rays or an electron beam. The bone proteins were extracted and used to determine the concentrations of total protein and BMP 2 and 7. Results Decreases in total protein and BMP 2 and 7 concentrations were observed. The decreases in total protein concentrations, in comparison with the respective control groups, were significant in the lyophilized and frozen samples that were irradiated at a dose of 50 kGy of gamma radiation and electron beam, with reductions of more than 30%. Significant decreases in the levels of BMP 2 and 7 were also observed at higher doses and especially through use of the electron beam. Conclusion The reductions in the concentrations of total proteins and osteoinductive proteins (BMP 2 and 7) were related to the radiation dose, i.e. they increased with higher doses of ionizing radiation type and the type of bone preservation. The largest reductions in concentrations were observed in the bones irradiated by means of an electron beam and at a dose of 50 kGy. However, this type of radiation and this high dose are not usual practices for sterilization of bone tissue. PMID:27069893

  3. Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Behnaz BAKHSHANDEH; Masoud SOLEIMANI; Nasser GHAEMI; Iman SHABANI

    2011-01-01

    Aim: Bioartificial bone tissue engineering is an increasingly popular technique to solve bone defect challenges. This study aimed to investigate the interactions between matrix composition and appropriate cell type, focusing on hydroxyapatite (HA), to achieve a more effective combination for bone regeneration.Methods: Human unrestricted somatic stem cells (USSCs) were isolated from placental cord blood. The cellular and molecular events during the osteo-induction of USSCs were evaluated for 21 d under the following conditions: (1) in basal culture, (2) supplemented with hydroxyapatite nanoparticle (nHA) suspension, and (3) seeded on electrospun aligned nanoflbrous poly-ε-caprolactone/poly-L-lactic acid/nHA (PCL/PLLA/nHA) scaffolds. The scaffolds were characterized using scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR) and tensile test.Results: Maintenance of USSCs for 21 d in basal or osteogenic culture resulted in significant increase in osteoblast differentiation. With nHA suspension, even soluble osteo-inductive additives were ineffective, probably due to induced apoptosis of the cells. In con-trast to the hindrance of proliferation by nHA suspension, the scaffolds improved cell growth. The scaffolds mimic the nanostructure of natural bone matrix with the combination of PLLA/PCL (organic phase) and HA (inorganic phase) offering a favorable surface topogra-phy, which was demonstrated to possess suitable properties for supporting USSCs. Quantitative measurement of osteogenic markers, enzymatic activity and mineralization indicated that the scaffolds did not disturb, but enhanced the osteogenic potential of USSCs.Moreover, the alignment of the fibers led to cell orientation during cell growth.Conclusion: The results demonstrated the synergism of PCL/PLLA/nHA nanoflbrous scaffolds and USSCs in the augmentation of osteo-genic differentiation. Thus, nHA grafted into PCI./PLLA scaffolds can be a suitable choice for bone tissue

  4. Bioactive Ti metal analogous to human cancellous bone: Fabrication by selective laser melting and chemical treatments.

    Science.gov (United States)

    Pattanayak, Deepak K; Fukuda, A; Matsushita, T; Takemoto, M; Fujibayashi, S; Sasaki, K; Nishida, N; Nakamura, T; Kokubo, T

    2011-03-01

    Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45 μm particle size. The results show that a fully dense plate thinner than 1.8 mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30 μm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35-120 MPa when the porosity was in the range 75-55%. Porous Ti metals fabricated by SLM were heat-treated at 1300 °C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3 days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12 weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants.

  5. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells.

    Science.gov (United States)

    Chen, Pei-Min; Yen, Men-Luh; Liu, Ko-Jiunn; Sytwu, Huey-Kang; Yen, B-Linju

    2011-07-18

    In recent years, a large number of studies have contributed to our understanding of the immunomodulatory mechanisms used by multipotent mesenchymal stem cells (MSCs). Initially isolated from the bone marrow (BM), MSCs have been found in many tissues but the strong immunomodulatory properties are best studied in BM MSCs. The immunomodulatory effects of BM MSCs are wide, extending to T lymphocytes and dendritic cells, and are therapeutically useful for treatment of immune-related diseases including graft-versus-host disease as well as possibly autoimmune diseases. However, BM MSCs are very rare cells and require an invasive procedure for procurement. Recently, MSCs have also been found in fetal-stage embryo-proper and extra-embryonic tissues, and these human fetal MSCs (F-MSCs) have a higher proliferative profile, and are capable of multilineage differentiation as well as exert strong immunomodulatory effects. As such, these F-MSCs can be viewed as alternative sources of MSCs. We review here the current understanding of the mechanisms behind the immunomodulatory properties of BM MSCs and F-MSCs. An increase in our understanding of MSC suppressor mechanisms will offer insights for prevalent clinical use of these versatile adult stem cells in the near future.

  6. Islet neogenesis potential of human adult stem cells and its applications in cell replacement therapy for diabetes

    Directory of Open Access Journals (Sweden)

    Bhonde RR

    2008-11-01

    Full Text Available In recent years regenerative biology has reached to greater heights due to its therapeutic potential in treating degenerative diseases; as they are not curable by modern medicine. With the advent of research in stem cells and developmental biology the regenerative potential of adult resident stem cells is becoming clearer. The long term objective of regenerative medicine or cell therapy is to treat patients with their own stem cells. These stem cells could be derived from the diseased organs such as skin, liver, pancreas etc. or from reservoirs of multipotent stem cells such as bone marrow or cord blood.Manipulating the ability of tissue resident stem cells as well as from multipotent reservoirs such as bone marrow, umbilical cord and cord blood to give rise to endocrine cells may open new avenues in the treatment of diabetes. A better understanding of stem cell biology would almost certainly allow for the establishment of efficient and reliable cell transplantation experimental programs in the clinic. We show here that multipotent mesenchymal stem cells can be isolated from various sources such as the bone marrow, placenta, umbilical cord. Upon stimulation with specific growth factors they differentiate into islet like clusters (ILCs. When ILCs obtained from the above mentioned sources were transplanted in experimental diabetic mice, restoration of normoglycemia was observed within three weeks of transplantation with concomitant increase in the body weight. These euglycemic mice exhibited normal glucose tolerance test indicating normal utilization of glucose. Allthough the MSCs isolated from all the sources had the same characteristics; they showed significant differences in their islet differentiation potential. ILCs isolated for the human bone marrow did not show any pancreatic hormones in vitro, but upon transplantation they matured into insulin and somatostatin producing hormones. Placental MSCs as well as ILCs showed insulin trascripts

  7. Paramagnetic and crystallographic effects of low temperature ashing on human bone and tooth enamel.

    Science.gov (United States)

    Tochon-Danguy, H J; Very, J M; Geoffroy, M; Baud, C A

    1978-02-28

    Low temperature ashing by excited gas (LTA) causes crystallographic and paramagnetic alterations of the human bone and tooth enamel mineral. On the one hand, LTA induces variations of the alpha lattice parameter. These variations depend upon the nature of the gas used, but are little affected by its degree of excitation. Trapping of gas molecules in the crystal structure is demonstrated. On the other hand, LTA produces two preponderant paramagnetic centers in bone and enamel samples at 20 degrees C. Their inorganic origin clearly indicated. One of the two radicals has been identified as O3- (g1 = 2.002, g2 = 2.010, g3 = 2.016) and the other as (CO3-3 (parallel = 1.996, g = perpendicular 2.003). Variations of the alpha lattice parameter and trapping of paramagnetic gas species do not seem to be directly related.

  8. Zone-dependent changes in human vertebral trabecular bone: clinical implications

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Ebbesen, Ebbe Nils; Mosekilde, Lis

    2002-01-01

    . The aim of the present study was, therefore, to investigate whether such zone-specific differences could be identified by static histomorphometric measures. The material comprised 48 individuals (24 women aged 19-97 years, and 24 men aged 23-95 years). Three of the women had a known fracture of the L-2......We have previously shown that there are pronounced age-related changes in human vertebral cancellous bone density and microarchitecture. However, the magnitude of these changes seemed to be dependent on zone location in the vertebral body-the central third vs. the areas adjacent to the endplates....... The histomorphometry was performed on both the whole section and on the separate zones (central and sub-endplate zone). The results showed that trabecular bone volume, trabecular number, and connectivity density decreased significantly faster with age, whereas marrow space star volume increased significantly faster...

  9. Proteome Changes of Human Bone Marrow Mesenchymal Stem Cells Induced by 1,4-Benzoquinone

    Science.gov (United States)

    2016-01-01

    Benzene is metabolized to hydroquinone in liver and subsequently transported to bone marrow for further oxidization to 1,4-benzoquinone (1,4-BQ), which may be related to the leukemia and other blood disorders. In the present study, we investigated the proteome profiles of human primary bone marrow mesenchymal stem cells (hBM-MSCs) treated by 1,4-BQ. We identified 32 proteins that were differentially expressed. Two of them, HSP27 and Vimentin, were verified at both mRNA and protein levels and their cellular localization was examined by immunofluorescence. We also found increased mRNA level of RAP1GDS1, a critical factor of metabolism that has been identified as a fusion partner in various hematopoietic malignancies. Therefore, these differentially expressed proteins can play important roles in benzene-mediated hematoxicity. PMID:28119923

  10. 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.

  11. Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

    Science.gov (United States)

    Papanagiotou, Marianthi; Dailiana, Zoe H; Karachalios, Theophilos; Varitimidis, Sokratis; Hantes, Michael; Dimakopoulos, Georgios; Vlychou, Marianna; Malizos, Konstantinos N

    2017-01-01

    AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of nonunions. METHODS Bone morphogenetic proteins (BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients (80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent joints were also carried out. Factors related to the patient (age, gender), the nonunion (location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure (graft and fixation type, amount of rhBMP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ2 test was performed. RESULTS Eighty point nine percent of the nonunions treated with rhBMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients (17.8%) and it was apparent in the routine radiological evaluation of the nonunion site, in a mean time of 5.5 mo after the rhBMP-7 application (range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhBMP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient’s gender was the only important factor for the development of heterotopic ossification (P = 0.007). CONCLUSION Heterotopic ossification after the use of rhBMP-7 in nonunions was

  12. 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

  13. Matrigel Enhances in vitro Bone Differentiation of Human Marrow-derived Mesenchymal Stem Cells

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    Mohamadreza Baghaban Eslaminejad

    2010-01-01

    Full Text Available The use of co-culture cells as well as extra cellular matrix are among those strategies that have been employed to direct mesenchymal stem cell (MSC bone differentiation in culture. In this regard, there is no study considering the effects of Matrigel on mesenchymal stem cell (MSC in vitro bone differentiation. This was the subject of the present study. Materials and MethodsHuman passaged-3 MSCs isolated from the marrow aspirates were seeded on either Matrigel or conventional polystyrene plastic surfaces (as control for 10 days. To compare the cell proliferation in two cultures, the cell numbers were determined during the cultivation period. For bone differentiation, the confluent cultures from either group were provided with osteogenic medium and incubated for 21 days during which the alkaline phosphates (ALP activity, culture mineralization and the expression of some bone-related genes were quantified and statistically compared.ResultsMTT assay indicated thatMatrigel-cultivated cells underwent statistically less proliferation than polystyrene-cultivated cells (P<0.05. Regarding the osteogenic differentiation, ALP activity was significantly high in Matrigel versus plastic cultures. Calcium deposition in Matrigel cultures tended to be significantly extensive compared with that of control cultures (2.533±0.017 versus 0.607±0.09 mM. Furthermore, according to the semi-quantitative RT-PCR analysis, compared with polystyrene plastic surface, Matrigel seemed to provide a microenvironment in which human MSC expressed osteocalcin and collagen I genes in a significantly higher level. ConclusionCollectively it seems that Matrigel could be considered as an appropriate matrix for MSC osteogenic differentiation.

  14. Directed migration of human bone marrow mesenchymal stem cells in a physiological direct current electric field

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    Z Zhao

    2011-11-01

    Full Text Available At sites of bone fracture, naturally-occurring electric fields (EFs exist during healing and may guide cell migration. In this study, we investigated whether EFs could direct the migration of bone marrow mesenchymal stem cells (BM-MSCs, which are known to be key players in bone formation. Human BM-MSCs were cultured in direct current EFs of 10 to 600 mV/mm. Using time-lapse microscopy, we demonstrated that an EF directed migration of BM-MSCs mainly to the anode. Directional migration occurred at a low threshold and with a physiological EF of ~25 mV/mm. Increasing the EF enhanced the MSC migratory response. The migration speed peaked at 300 mV/mm, at a rate of 42 ±1 µm/h, around double the control (no EF migration rate. MSCs showed sustained response to prolonged EF application in vitro up to at least 8 h. The electrotaxis of MSCs with either early (P3-P5 or late (P7-P10 passage was also investigated. Migration was passage-dependent with higher passage number showing reduced directed migration, within the range of passages examined. An EF of 200 mV/mm for 2 h did not affect cell senescence, phenotype, or osteogenic potential of MSCs, regardless of passage number within the range tested (P3-P10. Our findings indicate that EFs are a powerful cue in directing migration of human MSCs in vitro. An applied EF may be useful to control or enhance migration of MSCs during bone healing.

  15. Features of hand-foot crawling behavior in human adults.

    Science.gov (United States)

    Maclellan, M J; Ivanenko, Y P; Cappellini, G; Sylos Labini, F; Lacquaniti, F

    2012-01-01

    Interlimb coordination of crawling kinematics in humans shares features with other primates and nonprimate quadrupeds, and it has been suggested that this is due to a similar organization of the locomotor pattern generators (CPGs). To extend the previous findings and to further explore the neural control of bipedal vs. quadrupedal locomotion, we used a crawling paradigm in which healthy adults crawled on their hands and feet at different speeds and at different surface inclinations (13°, 27°, and 35°). Ground reaction forces, limb kinematics, and electromyographic (EMG) activity from 26 upper and lower limb muscles on the right side of the body were collected. The EMG activity was mapped onto the spinal cord in approximate rostrocaudal locations of the motoneuron pools to characterize the general features of cervical and lumbosacral spinal cord activation. The spatiotemporal pattern of spinal cord activity significantly differed between quadrupedal and bipedal gaits. In addition, participants exhibited a large range of kinematic coordination styles (diagonal vs. lateral patterns), which is in contrast to the stereotypical kinematics of upright bipedal walking, suggesting flexible coupling of cervical and lumbosacral pattern generators. Results showed strikingly dissimilar directional horizontal forces for the arms and legs, considerably retracted average leg orientation, and substantially smaller sacral vs. lumbar motoneuron activity compared with quadrupedal gait in animals. A gradual transition to a more vertical body orientation (increasing the inclination of the treadmill) led to the appearance of more prominent sacral activity (related to activation of ankle plantar flexors), typical of bipedal walking. The findings highlight the reorganization and adaptation of CPG networks involved in the control of quadrupedal human locomotion and a high specialization of the musculoskeletal apparatus to specific gaits.

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

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    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.

  17. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

    DEFF Research Database (Denmark)

    Klefter, O.; Feldt-Rasmussen, U.

    2009-01-01

    OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...

  18. Bone health and risk factors of cardiovascular disease--a cross-sectional study in healthy young adults.

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    Satu Pirilä

    Full Text Available OBJECTIVE: Both osteoporosis and cardiovascular disease (CVD are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low physical activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD and turnover markers (BTMs in apparently healthy cohort. DESIGN: A cross-sectional assessment of 155 healthy 32-year-old adults (74 males was performed for skeletal status, CVD risk factors and lifestyle factors. METHODS: We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP, collagen I carboxy-terminal telopeptide (ICTP and urine collagen I aminoterminal telopeptide (U-NTX, as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were assessed using DXA scanning. Associations were tested with partial correlations in crude and adjusted models. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria with multivariate analysis. RESULTS: Osteocalcin and P1NP correlated inversely with insulin (R = -0.243, P = 0.003 and R = -0.187, P = 0.021 and glucose (R = -0.213, P = 0.009 and R = -0.190, P = 0.019, but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (R = -0.162, P = 0.053 and R = -0.093, P = 0.266 and with glucose (R = -0.099, P = 0.240 and R = -0.133, P = 0.110, respectively. Whole body BMD associated inversely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model. CONCLUSIONS: In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass

  19. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

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    Junjie Guan

    Full Text Available Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP, and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

  20. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

    Science.gov (United States)

    Guan, Junjie; Zhang, Jieyuan; Li, Haiyan; Zhu, Zhenzhong; Guo, Shangchun; Niu, Xin; Wang, Yang; Zhang, Changqing

    2015-01-01

    Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs) are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP), and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP) were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

  1. Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma

    DEFF Research Database (Denmark)

    Maspero, Jorge; Backer, Vibeke; Yao, Ruji;

    2014-01-01

    asthma. METHODS: Adults with mild-moderate persistent asthma who did not receive ICS for ≥3 months were randomized to MF 400 μg once daily (QD) in the evening (pm), MF 200 μg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate (FP) 250 μg twice daily. Included patients had 25-hydroxy...

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

    DEFF Research Database (Denmark)

    Thudium, Christian S; Moscatelli, Ilana; Flores, Carmen

    2014-01-01

    that osteoclasts are important for regulating osteoblast activity. To illuminate the role of the osteoclast in controlling bone remodeling, we transplanted irradiated skeletally mature 3-month old wild-type mice with hematopoietic stem cells (HSCs) to generate either an osteoclast-rich or osteoclast-poor adult...... osteopetrosis model. We used fetal liver HSCs from (1) oc/oc mice, (2) RANK KO mice, and (3) compared these to wt control cells. TRAP5b activity, a marker of osteoclast number and size, was increased in the oc/oc recipients, while a significant reduction was seen in the RANK KO recipients. In contrast, the bone...

  3. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

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    Nadja Larsen

    Full Text Available BACKGROUND: Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control. METHODS AND FINDINGS: The study included 36 male adults with a broad range of age and body-mass indices (BMIs, among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR and in a subgroup of subjects (N = 20 by tag-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03. Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04 but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02 and positively correlated with plasma glucose (P = 0.04. CONCLUSIONS: The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.

  4. Dose to red bone marrow of infants, children and adults from radiation of natural origin

    Energy Technology Data Exchange (ETDEWEB)

    Kendall, G M [Childhood Cancer Research Group, University of Oxford, 57 Woodstock Road, Oxford OX2 6HJ (United Kingdom); Fell, T P; Harrison, J D [Health Protection Agency, Radiation Protection Division, CRCE, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom)], E-mail: Gerald.Kendall@ccrg.ox.ac.uk

    2009-06-15

    Natural radiation sources contribute much the largest part of the radiation exposure of the average person. This paper examines doses from natural radiation to the red bone marrow, the tissue in which leukaemia is considered to originate, with particular emphasis on doses to children. The most significant contributions are from x-rays and gamma rays, radionuclides in food and inhalation of isotopes of radon and their decay products. External radiation sources and radionuclides other than radon dominate marrow doses at all ages. The variation with age of the various components of marrow dose is considered, including doses received in utero and in each year up to the age of 15. Doses in utero include contributions resulting from the ingestion of radionuclides by the mother and placental transfer to the foetus. Postnatal doses include those from radionuclides in breast-milk and from radionuclides ingested in other foods. Doses are somewhat higher in the first year of life and there is a general slow decline from the second year of life onwards. The low linear energy transfer (LET) component of absorbed dose to the red bone marrow is much larger than the high LET component. However, because of the higher radiation weighting factor for the latter it contributes about 40% of the equivalent dose incurred up to the age of 15.

  5. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

    DEFF Research Database (Denmark)

    Klefter, Oliver; Feldt-Rasmussen, Ulla

    2009-01-01

    performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase......OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due...... to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...

  6. Human herpesvirus 8 seropositivity among sexually active adults in Uganda.

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    Fatma M Shebl

    Full Text Available INTRODUCTION: Sexual transmission of human herpesvirus 8 (HHV8 has been implicated among homosexual men, but the evidence for sexual transmission among heterosexual individuals is controversial. We investigated the role of sexual transmission of HHV8 in a nationally representative sample in Uganda, where HHV8 infection is endemic and transmitted mostly during childhood. MATERIALS AND METHODS: The study population was a subset of participants (n = 2681 from a population-based HIV/AIDS serobehavioral survey of adults aged 15-59 years conducted in 2004/2005. High risk for sexual transmission was assessed by questionnaire and serological testing for HIV and herpes simplex virus 2. Anti-HHV8 antibodies were measured using two enzyme immunoassays targeting synthetic peptides from the K8.1 and orf65 viral genes. The current study was restricted to 2288 sexually active adults. ORs and 95% CIs for HHV8 seropositivity were estimated by fitting logistic regression models with a random intercept using MPLUS and SAS software. RESULTS: The weighted prevalence of HHV8 seropositivity was 56.2%, based on 1302 seropositive individuals, and it increased significantly with age (P(trend<0.0001. In analyses adjusting for age, sex, geography, education, and HIV status, HHV8 seropositivity was positively associated with reporting two versus one marital union (OR:1.52, 95% CI: 1.17-1.97 and each unit increase in the number of children born (OR: 1.04, 95% CI: 1.00-1.08, and was inversely associated with ever having used a condom (OR: 0.64, 95% CI: 0.45-0.89. HHV8 seropositivity was not associated with HIV (P = 0.660 or with herpes simplex virus 2 (P = 0.732 seropositivity. Other sexual variables, including lifetime number of sexual partners or having had at least one sexually transmitted disease, and socioeconomic variables were unrelated to HHV8 seropositivity. CONCLUSION: Our findings are compatible with the conclusion that sexual transmission of HHV8 in

  7. Responsiveness of human prostate carcinoma bone tumors to interleukin-2 therapy in a mouse xenograft tumor model.

    Science.gov (United States)

    Kocheril, S V; Grignon, D J; Wang, C Y; Maughan, R L; Montecillo, E J; Talati, B; Tekyi-Mensah, S; Pontes, J e; Hillman, G G

    1999-01-01

    We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotransplanted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

  8. Changes in the stiffness of the human tibial cartilage-bone complex in early-stage osteoarthrosis

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    Cylindrical human tibial cartilage-bone unit specimens were removed from 9 early-stage medial osteoarthrotic (OA) tibiae (mean age 74 years) and 10 normal age-matched tibiae (mean age 73 years). These specimens were divided into 4 groups: OA, lateral comparison, medial age-matched, and lateral age......-matched and were tested to 0.5% bone strain with a novel technique to obtain the stiffnesses of both cartilage and bone simultaneously. We found a pronounced reduction in the stiffnesses of OA cartilage and subchondral bone when compared with the medial age-matched group. OA cartilage was significantly thinner...... than that of the lateral comparison and the medial age-matched control groups. However, this reduction in thickness was not correlated with the reduction in stiffness for OA cartilage. The stiffnesses did not correlate between OA cartilage and bone, whereas the stiffness relationships between cartilage...

  9. Study on Bone Mineral Density and its Influencing Factors among 1 214 Older Adults in Xuhui District, Shanghai

    Institute of Scientific and Technical Information of China (English)

    Jian-ping CHEN; Mao-hua MIAO; Li-feng ZHOU; Jie YANG; Guang-hua LU; Xiao-ping ZHOU; Hui-qin YU; Er-sheng GAO

    2006-01-01

    Objective To understand the status of the forearm bone mineral density (BMD) in older adults, and to identify the potentialfactors influencing BMD.Methods A total of 1 214 older adults were examined, in Tianlin, Fenglin and Xietu sub-districts, of Xuhui district, Shanghai. BMD was tested at the left forearm,including distal radius and ulna 1/3 total, distalradius where the distance of radius and ulna is 8 mm, ultra-distal radius, by single energy X-ray densitometer.Results The BMD at all of the four sites decreased with the age increased. The average BMD was higher in male than in female for the same age and measured site.Distal radius 1/3 total had the highest BMD among the four sites. The incidence of low BMD and osteoporosis in distal forearm 1/3 radius total ascended with the age increased.Multiplied logistic regression showed that males had a lower risk to be low BMD (OR=0.19) compared with female. Compared with the group aged from 50 to 54, the odds ratio in the group aged from 55 to 59, 60 to 64, and 65 to 70 were respectively 3.17,5.13, 15.03. Compared with those whose monthly salary was less than 1 000, the odds ratio was 0.70 in those whose salary was more than 1 000.Conclusion The incidence of low BMD was high in older adults, and it is related with sex, age, monthly salary.

  10. NOTE: A preliminary study for non-invasive quantification of manganese in human hand bones

    Science.gov (United States)

    Aslam; Pejović-Milić, A.; Chettle, D. R.; McNeill, F. E.; Pysklywec, M. W.; Oudyk, J.

    2008-10-01

    Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12 ± 0.68 µg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16 0.78 µg Mn/g Ca and mean value of 0.63 ± 0.30 µg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.

  11. Easily-handled method to isolate mesenchymal stem cells from coagulated human bone marrow samples

    Institute of Scientific and Technical Information of China (English)

    Heng-Xiang; Wang; Zhi-Yong; Li; Zhi-Kun; Guo; Zi-Kuan; Guo

    2015-01-01

    AIM:To establish an easily-handled method to isolate mesenchymal stem cells(MSCs) from coagulated human bone marrow samples. METHODS: Thrombin was added to aliquots of seven heparinized human bone marrow samples to mimic marrow coagulation. The clots were untreated,treated with urokinase or mechanically cut into pieces before culture for MSCs. The un-coagulated samples and the clots were also stored at 4 ℃ for 8 or 16 h before the treatment. The numbers of colony-forming unit-fibroblast(CFU-F) in the different samples were determined. The adherent cells from different groups were passaged and their surface profile was analyzed with flow cytometry. Their capacities of in vitro osteogenesis and adipogenesis were observed after the cells were exposed to specific inductive agents.RESULTS: The average CFU-F number of urokinasetreated samples(16.85 ± 11.77/106) was comparable to that of un-coagulated control samples(20.22 ± 10.65/106,P = 0.293),which was significantly higher than those of mechanically-cut clots(6.5 ± 5.32/106,P < 0.01) and untreated clots(1.95 ± 1.86/106,P < 0.01). The CFU-F numbers decreased after samples were stored,but those of control and urokinase-treated clots remained higher than the other two groups. Consistently,the numbers of the attached cells at passage 0 were higher in control and urokinase-treated clots than those of mechanically-cut clots and untreated clots.The attached cells were fibroblast-like in morphology and homogenously positive for CD44,CD73 and CD90,and negative for CD31 and CD45. Also,they could be induced to differentiate into osteoblasts and adipocytes in vitro. CONCLUSION: Urokinase pretreatment is an optimal strategy to isolate MSCs from human bone marrow samples that are poorly aspirated and clotted.

  12. A high volume extraction and purification method for recovering DNA from human bone.

    Science.gov (United States)

    Marshall, Pamela L; Stoljarova, Monika; Schmedes, Sarah E; King, Jonathan L; Budowle, Bruce

    2014-09-01

    DNA recovery, purity and overall extraction efficiency of a protocol employing a novel silica-based column, Hi-Flow(®) (Generon Ltd., Maidenhead, UK), were compared with that of a standard organic DNA extraction methodology. The quantities of DNA recovered by each method were compared by real-time PCR and quality of DNA by STR typing using the PowerPlex(®) ESI 17 Pro System (Promega Corporation, Madison, WI) on DNA from 10 human bone samples. Overall, the Hi-Flow method recovered comparable quantities of DNA ranging from 0.8ng±1 to 900ng±159 of DNA compared with the organic method ranging from 0.5ng±0.9 to 855ng±156 of DNA. Complete profiles (17/17 loci tested) were obtained for at least one of three replicates for 3/10 samples using the Hi-Flow method and from 2/10 samples with the organic method. All remaining bone samples yielded partial profiles for all replicates with both methods. Compared with a standard organic DNA isolation method, the results indicated that the Hi-Flow method provided equal or improved recovery and quality of DNA without the harmful effects of organic extraction. Moreover, larger extraction volumes (up to 20mL) can be employed with the Hi-Flow method which enabled more bone sample to be extracted at one time.

  13. Mechanical strength of ceramic scaffolds reinforced with biopolymers is comparable to that of human bone.

    Science.gov (United States)

    Henriksen, S S; Ding, M; Juhl, M Vinther; Theilgaard, N; Overgaard, S

    2011-05-01

    Eight groups of calcium-phosphate scaffolds for bone implantation were prepared of which seven were reinforced with biopolymers, poly lactic acid (PLA) or hyaluronic acid in different concentrations in order to increase the mechanical strength, without significantly impairing the microarchitecture. Controls were un-reinforced calcium-phosphate scaffolds. Microarchitectural properties were quantified using micro-CT scanning. Mechanical properties were evaluated by destructive compression testing. Results showed that adding 10 or 15% PLA to the scaffold significantly increased the mechanical strength. The increase in mechanical strength was seen as a result of increased scaffold thickness and changes to plate-like structure. However, the porosity was significantly lowered as a consequence of adding 15% PLA, whereas adding 10% PLA had no significant effect on porosity. Hyaluronic acid had no significant effect on mechanical strength. The novel composite scaffold is comparable to that of human bone which may be suitable for transplantation in specific weight-bearing situations, such as long bone repair.

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

    Science.gov (United States)

    Sroga, Grażyna E; Siddula, Alankrita; Vashishth, Deepak

    2015-01-01

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

  15. Human Dental Pulp-Derived Cells Produce Bone-Like Tissue and Exhibit Bone Cell-Like Responsiveness to Mechanical Loading

    DEFF Research Database (Denmark)

    Kraft, David Christian Evar; Melsen, Birte; Bindslev, Dorthe Arenholt

    2010-01-01

    Recent studies have shown that dental pulp cells possess stem cell like potential and thus may be potential candidates for tissue engineering purposes particularly in the oro-facial region. Successful tissue engineering ideally requires that newly formed bone adapts its mass, shape, and trabecular...... and characterize cell lines from human 3rd molar dental pulp tissue to determine whether human dental pulp-derived cells (DPCs) are osteogenic and responsive to mechanical loading by pulsating fluid flow (PFF) in vitro. Methods: Human DPCs used for this study were characterized by measuring proliferation...

  16. Molecular cloning of complementary DNA for human medullasin: an inflammatory serine protease in bone marrow cells.

    Science.gov (United States)

    Okano, K; Aoki, Y; Sakurai, T; Kajitani, M; Kanai, S; Shimazu, T; Shimizu, H; Naruto, M

    1987-07-01

    Medullasin, an inflammatory serine protease in bone marrow cells, modifies the functions of natural killer cells, monocytes, and granulocytes. We have cloned a medullasin cDNA from a human acute promyelocytic cell (ML3) cDNA library using oligonucleotide probes synthesized from the information of N-terminal amino acid sequence of natural medullasin. The cDNA contained a long open reading frame encoding 237 amino acid residues beginning from the second amino acid of natural meduallasin. The deduced amino acid sequence of medullasin shows a typical serine protease structure, with 41% homology with pig elastase 1.

  17. The proteomic dataset for bone marrow derived human mesenchymal stromal cells: Effect of in vitro passaging

    Directory of Open Access Journals (Sweden)

    Samuel T. Mindaye

    2015-12-01

    Full Text Available Bone-marrow derived mesenchymal stromal cells (BMSCs have been in clinical trials for therapy. One major bottleneck in the advancement of BMSC-based products is the challenge associated with cell isolation, characterization, and ensuring cell fitness over the course of in vitro cell propagation steps. The data in this report is part of publications that explored the proteomic changes following in vitro passaging of BMSCs [4] and the molecular heterogeneity in cultures obtained from different human donors [5,6].The methodological details involving cell manufacturing, proteome harvesting, protein identification and quantification as well as the bioinformatic analyses were described to ensure reproducibility of the results.

  18. Human calcium metabolism including bone resorption measured with {sup 41}Ca tracer

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.P.H.T. [Lawrence Livermore National Lab., CA (United States); King, J.C. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Vieira, N.E. [National Inst. of Child Health and Human Development, Bethesda, MD (United States); Woodhouse, L.R. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Yergey, A.L. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)

    1996-08-01

    Accelerator mass spectrometry is so sensitive to small quantities of {sup 41}Ca that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, {sup 41}Ca tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state. Resorbing bone may thus be directly measured. We have tested such a protocol against a conventional stable isotope experiment with good agreement.

  19. Rietveld Refinement on X-Ray Diffraction Patterns of Bioapatite in Human Fetal Bones

    Science.gov (United States)

    Meneghini, Carlo; Dalconi, Maria Chiara; Nuzzo, Stefania; Mobilio, Settimio; Wenk, Rudy H.

    2003-01-01

    Bioapatite, the main constituent of mineralized tissue in mammalian bones, is a calcium-phosphate-based mineral that is similar in structure and composition to hydroxyapatite. In this work, the crystallographic structure of bioapatite in human fetuses was investigated by synchrotron radiation x-ray diffraction (XRD) and microdiffraction (μ-XRD) techniques. Rietveld refinement analyses of XRD and μ-XRD data allow for quantitative probing of the structural modifications of bioapatite as functions of the mineralization process and gestational age. PMID:12609904

  20. Immunoreactivity of thymosin beta 4 in human foetal and adult genitourinary tract

    Science.gov (United States)

    Nemolato, S.; Cabras, T.; Fanari, M.U.; Cau, F.; Fanni, D.; Gerosa, C.; Manconi, B.; Messana, I.; Castagnola, M.; Faa, G.

    2010-01-01

    Thymosin beta 4 (Tβ4) is a member of the beta-thymosins family, a family of peptides playing essential roles in many cellular functions. Our recent studies suggested Tβ4 plays a key role in the development of human salivary glands and the gastrointestinal tract. The aim of this study was to analyse the presence of Tβ4 in the human adult and foetal genitourinary tract. Immunolocalization of Tβ4 was studied in autoptic samples of kidney, bladder, uterus, ovary, testicle and prostate obtained from four human foetuses and four adults. Presence of the peptide was observed in cells of different origin: in surface epithelium, in gland epithelial cells and in the interstitial cells. Tβ4 was mainly found in adult and foetal bladder in the transitional epithelial cells; in the adult endometrium, glands and stromal cells were immunoreactive for the peptide; Tβ4 was mainly localized in the glands of foetal prostate while, in the adults a weak Tβ4 reactivity was restricted to the stroma. In adult and foetal kidney, Tβ4 reactivity was restricted to ducts and tubules with completely spared glomeruli; a weak positivity was observed in adult and foetal oocytes; immunoreactivity was mainly localized in the interstitial cells of foetal and adult testis. In this study, we confirm that Tβ4 could play a relevant role during human development, even in the genitourinary tract, and reveal that immunoreactivity for this peptide may change during postnatal and adult life. PMID:21263742

  1. 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

  2. A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone

    Institute of Scientific and Technical Information of China (English)

    LING Li-jun; WANG Feng; WANG Shui; LIU Xiao-an; SHEN En-chao; DING Qiang; LU Chao; XU Jian; CAO Qin-hong; ZHU Hai-qing

    2008-01-01

    Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.Methods Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1x105, 1x106 human breast cancer stem-like cells, and 1x106 parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1x106 MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR). Results Our results demonstrated that cells in implanted human bones of group B, which received 1x106 cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P=0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest. Conclusions In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.

  3. A century of trends in adult human height

    DEFF Research Database (Denmark)

    Sørensen, Thorkild Ingvor A; Zimmermann, Esther

    2016-01-01

    in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over...

  4. Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Suna, E-mail: wangs3@mail.nih.gov; Zhou, Yifu; Andreyev, Oleg; Hoyt, Robert F.; Singh, Avneesh; Hunt, Timothy; Horvath, Keith A.

    2014-04-15

    Studying the proliferative ability of human bone marrow derived mesenchymal stem cells in hypoxic conditions can help us achieve the effective regeneration of ischemic injured myocardium. Cardiac-type fatty acid binding protein (FABP3) is a specific biomarker of muscle and heart tissue injury. This protein is purported to be involved in early myocardial development, adult myocardial tissue repair and responsible for the modulation of cell growth and proliferation. We have investigated the role of FABP3 in human bone marrow derived mesenchymal stem cells under ischemic conditions. MSCs from 12 donors were cultured either in standard normoxic or modified hypoxic conditions, and the differential expression of FABP3 was tested by quantitative {sup RT}PCR and western blot. We also established stable FABP3 expression in MSCs and searched for variation in cellular proliferation and differentiation bioprocesses affected by hypoxic conditions. We identified: (1) the FABP3 differential expression pattern in the MSCs under hypoxic conditions; (2) over-expression of FABP3 inhibited the growth and proliferation of the MSCs; however, improved their survival in low oxygen environments; (3) the cell growth factors and positive cell cycle regulation genes, such as PCNA, APC, CCNB1, CCNB2 and CDC6 were all down-regulated; while the key negative cell cycle regulation genes TP53, BRCA1, CASP3 and CDKN1A were significantly up-regulated in the cells with FABP3 overexpression. Our data suggested that FABP3 was up-regulated under hypoxia; also negatively regulated the cell metabolic process and the mitotic cell cycle. Overexpression of FABP3 inhibited cell growth and proliferation via negative regulation of the cell cycle and down-regulation of cell growth factors, but enhances cell survival in hypoxic or ischemic conditions. - Highlights: • FABP3 expression pattern was studied in 12 human hypoxic-MSCs. • FABP3 mRNA and proteins are upregulated in the MSCs under hypoxic conditions.

  5. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Science.gov (United States)

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  6. Compressive properties of commercially available polyurethane foams as mechanical models for osteoporotic human cancellous bone

    Directory of Open Access Journals (Sweden)

    Shepherd Duncan ET

    2008-10-01

    Full Text Available Abstract Background Polyurethane (PU foam is widely used as a model for cancellous bone. The higher density foams are used as standard biomechanical test materials, but none of the low density PU foams are universally accepted as models for osteoporotic (OP bone. The aim of this study was to determine whether low density PU foam might be suitable for mimicking human OP cancellous bone. Methods Quasi-static compression tests were performed on PU foam cylinders of different lengths (3.9 and 7.7 mm and of different densities (0.09, 0.16 and 0.32 g.cm-3, to determine the Young's modulus, yield strength and energy absorbed to yield. Results Young's modulus values were 0.08–0.93 MPa for the 0.09 g.cm-3 foam and from 15.1–151.4 MPa for the 0.16 and 0.32 g.cm-3 foam. Yield strength values were 0.01–0.07 MPa for the 0.09 g.cm-3 foam and from 0.9–4.5 MPa for the 0.16 and 0.32 g.cm-3 foam. The energy absorbed to yield was found to be negligible for all foam cylinders. Conclusion Based on these results, it is concluded that 0.16 g.cm-3 PU foam may prove to be suitable as an OP cancellous bone model when fracture stress, but not energy dissipation, is of concern.

  7. Comparison of toxicity of benzene metabolite hydroquinone in hematopoietic stem cells derived from murine embryonic yolk sac and adult bone marrow.

    Directory of Open Access Journals (Sweden)

    Jie Zhu

    Full Text Available Benzene is an occupational toxicant and an environmental pollutant that potentially causes hematotoxicity and leukemia in exposed populations. Epidemiological studies suggest an association between an increased incidence of childhood leukemia and benzene exposure during the early stages of pregnancy. However, experimental evidence supporting the association is lacking at the present time. It is believed that benzene and its metabolites target hematopoietic stem cells (HSCs to cause toxicity and cancer in the hematopoietic system. In the current study, we compared the effects of hydroquinone (HQ, a major metabolite of benzene in humans and animals, on mouse embryonic yolk sac hematopoietic stem cells (YS-HSCs and adult bone marrow hematopoietic stem cells (BM-HSCs. YS-HSCs and BM-HSCs were isolated and enriched, and were exposed to HQ at increasing concentrations. HQ reduced the proliferation and the differentiation and colony formation, but increased the apoptosis of both YS-HSCs and BM-HSCs. However, the cytotoxic and apoptotic effects of HQ were more apparent and reduction of colony formation by HQ was more severe in YS-HSCs than in BM-HSCs. Differences in gene expression profiles were observed in HQ-treated YS-HSCs and BM-HSCs. Cyp4f18 was induced by HQ both in YS-HSCs and BM-HSCs, whereas DNA-PKcs was induced in BM-HSCs only. The results revealed differential effects of benzene metabolites on embryonic and adult HSCs. The study established an experimental system for comparison of the hematopoietic toxicity and leukemogenicity of benzene and metabolites during mouse embryonic development and adulthood.

  8. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  9. Response to: Comment on "Human adult neurogenesis across the ages: An immunohistochemical study".

    Science.gov (United States)

    Dennis, C V; Suh, L S; Rodriguez, M L; Kril, J J; Sutherland, G T

    2017-02-20

    It is with great interest that we read the comment by Marucci [1] referring to our publication "Human adult neurogenesis across the ages: An immunohistochemical study" [2]. Since the seminal paper of Eriksson et al. in 1998, human adult neurogenesis has become a major area of research in neuroscience [3]. Although an age-related decline in human adult neurogenesis is not disputed, opinions differ on the functional significance of the residual neuroblasts. This article is protected by copyright. All rights reserved.

  10. [Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].

    Science.gov (United States)

    Fan, Zhongkai; Cao, Yang; Zhang, Zhe; Zhang, Mingchao; Lu, Wei; Tang, Lei; Yao, Qi; Lu, Gang

    2012-10-01

    This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.

  11. Influence of object location in different FOVs on trabecular bone microstructure measurements of human mandible: a cone beam CT study

    NARCIS (Netherlands)

    Ibrahim, N.; Parsa, A.; Hassan, B.; van der Stelt, P.; Aartman, I.H.A.; Nambiar, P.

    2014-01-01

    The aim of this study was to assess the influence of different object locations in different fields of view (FOVs) of two cone beam CT (CBCT) systems on trabecular bone microstructure measurements of a human mandible. A block of dry human mandible was scanned at five different locations (centre, lef

  12. LOW MINERAL DENSITY OF A WEIGHT-BEARING BONE AMONG ADULT WOMEN IN A HIGH FERTILITY POPULATION

    Science.gov (United States)

    Stieglitz, Jonathan; Beheim, Bret A.; Trumble, Benjamin C.; Madimenos, Felicia C.; Kaplan, Hillard; Gurven, Michael

    2014-01-01

    Evolutionary theories of aging posit that greater reproductive effort causes somatic decline given a fundamental trade-off between investing energy in reproduction and repair. Few studies in high fertility human populations support this hypothesis, and problems of phenotypic correlation can obscure the expected trade-off between reproduction and somatic condition. This cross-sectional study investigates whether greater reproductive effort is associated with reduced calcaneal bone mineral density (BMD) among female Tsimane forager-farmers of lowland Bolivia. We also investigate whether female Tsimane BMD values are lower than sex- and age-matched US reference values, despite the fact that Tsimane engage in higher physical activity levels that can increase mechanical loading. To measure calcaneal BMD, quantitative ultrasonography was performed on 130 women (mean ± SD age = 36.6 ± 15.7, range = 15 – 75) that were recruited regardless of past or current reproductive status. Anthropometric and demographic data were collected during routine medical exams. As predicted, higher parity, short inter-birth interval, and earlier age at first birth are associated with reduced BMD among Tsimane women after adjusting for potential confounders. Population-level differences are apparent prior to the onset of reproduction, and age-related decline in BMD is greater among Tsimane compared to American women. Greater cumulative reproductive burden may lower calcaneal BMD individually and jointly with other lifestyle and heritable factors. Fitness impacts of kin transfers in adulthood may determine the value of investments in bone remodeling, and thus affect selection on age-profiles of bone mineral loss. PMID:25488367

  13. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

    Science.gov (United States)

    Jiang, Shih Sheng; Chen, Chung-Hsing; Tseng, Kuo-Yun; Tsai, Fang-Yu; Wang, Ming Jen; Chang, I-Shou; Lin, Jiunn-Liang; Lin, Shankung

    2011-07-01

    Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

  14. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

    Directory of Open Access Journals (Sweden)

    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  15. Increased adipogenesis in cultured embryonic chondrocytes and in adult bone marrow of dominant negative Erg transgenic mice.

    Directory of Open Access Journals (Sweden)

    Sébastien Flajollet

    Full Text Available In monolayer culture, primary articular chondrocytes have an intrinsic tendency to lose their phenotype during expansion. The molecular events underlying this chondrocyte dedifferentiation are still largely unknown. Several transcription factors are important for chondrocyte differentiation. The Ets transcription factor family may be involved in skeletal development. One family member, the Erg gene, is mainly expressed during cartilage formation. To further investigate the potential role of Erg in the maintenance of the chondrocyte phenotype, we isolated and cultured chondrocytes from the rib cartilage of embryos of transgenic mice that express a dominant negative form of Erg (DN-Erg during cartilage formation. DN-Erg expression in chondrocytes cultured for up to 20 days did not affect the early dedifferentiation usually observed in cultured chondrocytes. However, lipid droplets accumulated in DN-Erg chondrocytes, suggesting adipocyte emergence. Transcriptomic analysis using a DNA microarray, validated by quantitative RT-PCR, revealed strong differential gene expression, with a decrease in chondrogenesis-related markers and an increase in adipogenesis-related gene expression in cultured DN-Erg chondrocytes. These results indicate that Erg is involved in either maintaining the chondrogenic phenotype in vitro or in cell fate orientation. Along with the in vitro studies, we compared adipocyte presence in wild-type and transgenic mice skeletons. Histological investigations revealed an increase in the number of adipocytes in the bone marrow of adult DN-Erg mice even though no adipocytes were detected in embryonic cartilage or bone. These findings suggest that the Ets transcription factor family may contribute to the homeostatic balance in skeleton cell plasticity.

  16. Effect of alendronate on bone mineral density in adult patients with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Eshed, Varda; Benbassat, Carlos A; Laron, Zvi

    2006-04-01

    Severe short stature resulting from a deficiency in insulin-like growth factor-I (IGF-I) is a prominent feature of Laron syndrome (LS). Whether patients with LS are osteopenic or not, and whether they need treatment with bisphosphonates, remains uncertain. The aim of this study was to investigate the action of alendronate on the IGF-I-deficient bones of adult patients with LS and osteoporosis, as determined by dual X-ray absorptiometry . Seven patients (5 women and 2 men) of mean age 40.8+/-7.6 years and mean bone mass density (BMD) 0.843+/-0.06 g/cm2 (T score -2.9+/-0.5) at the lumbar spine and 0.734+/-0.11 g/cm2 (T score -2.2+/-0.9) at the femoral neck were treated with alendronate 70 mg once/weekly over a 12-month period. Treatment led to an increase of 5.3% in BMD (p=0.038) at the femoral neck. There was a similar trend at the lumbar spine, but the difference was not statistically significant (2.3%, p=0.34). Mean total alkaline phosphatase decreased by 14% from normal range at baseline (p=0.007). Urinary deoxypyridinoline levels, which were elevated at baseline (10+/-2.3 nM/mMcre), showed a nonsignificant change during treatment. Our study suggests that treatment with alendronate may have positive effects in patients with LS and low BMD on dual X-ray absorptiometry.

  17. The effect of nicotine on osteoinduction by recombinant human bone morphogenetic protein 2.

    Science.gov (United States)

    Tamura, K; Togo, Y; Kaihara, S; Hussain, A; Takahashi, K; Bessho, K

    2014-08-01

    Nicotine, one of the constituents of tobacco, is known to have an adverse effect on human health. We sought to clarify the interaction between nicotine and recombinant human bone morphogenetic protein 2 (rhBMP-2) in terms of osteogenesis in vitro and osteoinduction in vivo. Nicotine did not inhibit or stimulate alkaline phosphatase (ALP) activity or the amount of osteocalcin in C2C12 cells in the presence of rhBMP-2 in vitro. Ectopic bone formation using a collagen sponge containing rhBMP-2 was evaluated with and without nicotine after 21 days using radiographic, histological, biochemical, and immunohistochemical analyses. ALP activity in the medium-dose group (2.2±0.9IU/mg protein; P=0.047) and the high-dose group (2.0±0.1IU/mg protein; P=0.03) was significantly lower than in the control group. The calcium content in the medium-dose group (35.4±12.9μg/mg tissue; P=0.0099) and high-dose group (34.8±10.5μg/mg tissue; P=0.006) was significantly lower than in the control group. The number of vascular endothelial growth factor-positive cells in the high-dose group (671.9±57.3cells/mm(2); P=0.03) was significantly lower than in the control group. Results showed that nicotine did not inhibit the stimulatory effect of rhBMP-2 in vitro, but a high dose of nicotine inhibited bone formation in vivo by adversely affecting vascularization.

  18. Enhanced human bone marrow mesenchymal stem cell functions on cathodic arc plasma-treated titanium

    Directory of Open Access Journals (Sweden)

    Zhu W

    2015-12-01

    Full Text Available Wei Zhu,1 George Teel,1 Christopher M O’Brien,1 Taisen Zhuang,1 Michael Keidar,1 Lijie Grace Zhang1–3 1Department of Mechanical and Aerospace Engineering, 2Department of Biomedical Engineering, 3Department of Medicine, The George Washington University, Washington, DC, USA Abstract: Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium’s osseointegration involves inducing biomimetic nanotopography to enhance cell–implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications

  19. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  20. Naming the body (or the bones): Human remains, anthropological/medical collections, religious beliefs, and restitution.

    Science.gov (United States)

    Charlier, Philippe

    2014-04-01

    Human bones and biological remains conserved in anthropological, medical, and archaeological collections are foci of ethical debate, as recently illustrated by the affair of Charles Byrne's bones. In the near future, curators will have to choose between global conservation of all (or almost all) anthropological collections and systematic restitution to their original communities or families. Various proposals and examples of restitution and nonrestitution are given (with justifications) in order to support the concept that the body (especially the dead body) is not property. We propose that the only element supporting arguments in favor of restitution could be the name of the individual, highlighting the importance of all identification processes for such "artifacts." This is undoubtedly a universal value: naming the dead, identifying and then burying the person, i.e., reversing the progression along the timeline from individual to scientific specimen. Such elements could be of great interest to all universities and medical institutions that keep human remains in their collections for educational or historical purposes when they are confronted with ethical problems and/or repatriation requests.

  1. HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

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    F Cappello

    2009-06-01

    Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

  2. Multimodal imaging of the human temporal bone: A comparison of CT and optical scanning techniques

    Science.gov (United States)

    Voie, Arne H.; Whiting, Bruce; Skinner, Margaret; Neely, J. Gail; Lee, Kenneth; Holden, Tim; Brunsden, Barry

    2003-10-01

    A collaborative effort between Washington University in St. Louis and Spencer Technologies in Seattle, WA has been undertaken to create a multimodal 3D reconstruction of the human cochlea and vestibular system. The goal of this project is to improve the accuracy of in vivo CT reconstructions of implanted cochleae, and to expand the knowledge of high-resolution anatomical detail provided by orthogonal-plane optical sectioning (OPFOS). At WUSL, computed tomography (CT) images of the cochlea are used to determine the position of cochlear implant electrodes relative to target auditory neurons. The cochlear implant position is determined using pre- and post-operative CT scans. The CT volumes are cross-registered to align the semicircular canals and internal auditory canal, which have a unique configuration in 3-D space. The head of a human body donor was scanned with a clinical CT device, after which the temporal bones were removed, fixed in formalin and trimmed prior to scanning with a laboratory Micro CT scanner. Following CT, the temporal bones were sent to the OPFOS Imaging Lab at Spencer Technologies for a further analysis. 3-D reconstructions of CT and OPFOS imaging modalities were compared, and results are presented. [Work supported by NIDCD Grants R44-03623-5 and R01-00581-13.

  3. The morphology and morphometry of the foramina of the greater wing of the human sphenoid bone.

    Science.gov (United States)

    Reymond, Jerzy; Charuta, Anna; Wysocki, Jarosław

    2005-08-01

    The greater wing of the human sphenoid bone is pierced by several foramina, which contain, as a main element, the venous anastomoses between the interior of the skull and the extracranial veins. Since data concerning these foramina are scarce in the literature, studies comprising the frequency of occurrence and morphology of the foramina of the greater wing of the human sphenoid bone were undertaken on 100 macerated skulls. We found that the foramen ovale is divided into 2 or 3 components in 4.5% of cases. Moreover, the borders of the foramen ovale in some skulls were irregular and rough. This may suggest, on radiological images, the presence of morbid changes, which might be the sole anatomical variation. Concurrent with the foramen ovale are accessory foramina. The foramen of Vesalius and the cavernous foramen were present in 17% and 33% of cases, respectively. The foramen of Vesalius was always single and the cavernous foramen also occurred in multiple form. The foramen spinosus and the foramen rotundum occurred as permanent elements of the skulls studied. The mean area of the foramina measured, excluding the foramen ovale, was not considerable, which may suggest that they play a minor role in the dynamics of blood circulation in the venous system of the head.

  4. Expression of Odontogenic Genes in Human Bone Marrow Mesenchymal Stem Cells

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    Seyedeh Sara Bagheri

    2013-01-01

    Full Text Available Objective: Tooth loss is a common problem and since current tooth replacement methods cannot counter balance with biological tooth structures, regenerating natural tooth structures has become an ideal goal. A challenging problem in tooth regeneration is to find a proper clinically feasible cell to seed.This study was designed to investigate the odontogenic potential of human bone marrow mesenchymal stem cells (HBMSCs for seeding in tooth regeneration.Materials and Methods: In this experimental study, three pregnant Sprague Dawley (SD rats were used at the eleventh embryonic day and rat fetuses were removed surgically using semilunar flap under general anesthesia. The primary mandible was cut using a stereomicroscope. The epithelial and mesenchymal components were separated and the dissected oral epithelium was cultured for 3 days. We used flow cytometry analysis to confirm presence of mesenchymal stem cells and not hematopoietic cells and to demonstrate the presence of oral epithelium. Bone marrow mesenchymal stem cells (BMSCs and cultured oral epithelium were then co-cultured for 14 days. BMSCs cultured alone were used as controls. Expression of two odontogenic genes Pax9 and DMP1 was assessed using quantitative reverse transcription- polymerase chain reaction (RT-PCR.Results: Expression of two odontogenic genes, Pax9 and DMP1, were detected in BMSCs co-cultured with oral epithelium but not in the control group.Conclusion: Expression of Pax9 and DMP1 by human BMSCs in the proximity of odontogenic epithelium indicates odontogenic potential of these cells.

  5. Establishment and identification of fibroblast clones expressing human bone morphogenetic protein 2

    Institute of Scientific and Technical Information of China (English)

    Juan Wang; Weibin Sun; Chun Lu; Guixia Tang

    2005-01-01

    Objective:To establish fibroblasts stably expressing human bone morphogenetic protein 2 (hBMP2). Methods:Eukaryonic expression vector(pcDNA3.1-B2) was transduced into NIH3T3 cells using SofastTM, a new generation cationic polymer gene transfection reagent. The positive cell clones were selected with G418. The stable transfection and expression of BMP2 in the NIH3T3 cells were determined by RT-PCR and immunohistochemical stain. Results: BMP2 mRNA was transcripted and expressed in the transfected NIH3T3 cells. Conclusion: With positive compound transfection, outside human BMP2 gene can be successfully transducted into NIH3T3 cells, which is the key step to induce periodontal cells to osseous phenotypes.