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Sample records for bone resorbing activity

  1. Bacteroides gingivalis antigens and bone resorbing activity in root surface fractions of periodontally involved teeth

    Energy Technology Data Exchange (ETDEWEB)

    Patters, M.R.; Landsberg, R.L.; Johansson, L.A.; Trummel, C.L.; Robertson, P.R. (Department of Periodontology, University of Connecticut, School of Dental Medicine, Farmington, Connecticut, U.S.A.)

    1982-01-01

    Bone resorbing activity and the presence of antigens of Bacteroides gingivalis were assessed in plaque, calculus, cementum, and dentin obtained from roots of teeth previously exposed to periodontitis. Each fraction was obtained by scaling the root surface. The fraction were extracted by stirring and sonication, and the soluble centrifuged, sterilized, dialyzed, and adjusted to equivalent protein concentrations. Cementum and dentin extracts from impacted teeth were prepared similarly and served as controls. Stimulation of bone resorption by each extract was assessed in organ cultures of fetal rat bones by measurement of release of previously-incorporated /sup 45/Ca from the bone into the medium. In some groups of teeth, calculus and cementum were treated with acid prior to scaling. Citric acid washes were recovered and dialyzed. An enzyme-linked immunosorbent assay (ELISA) was used to assess the extracts for the presence of antigens reactive with an antiserum to B. gingivalis. Significant stimulation of bone resorption was found in all calculus and periodontally-involved cementum preparations. ELISA showed significant levels of B.gingivalis antigens in plaque, calculus, and cementum of periodontally-involved teeth, but not in involved dentin nor in cementum or dentin of impact teeth. Treatment with citric acid removed essentially all B.gingivalis antigens from cementum but not calculus. The results suggest that substances which stimulate bone resorption and substances which react with B. gingivalis antiserum are present in surface plaque, calculus, and cementum or periodontally-involved teeth. These substances are not present in cementum and dentin of impacted teeth nor in dentin of periodontally-involved teeth. Treatment by both scaling and citric demineralization will remove most of these substances from cementum of teeth previously exposed to periodontitis.

  2. Bacteroides gingivalis antigens and bone resorbing activity in root surface fractions of periodontally involved teeth

    International Nuclear Information System (INIS)

    Bone resorbing activity and the presence of antigens of Bacteroides gingivalis were assessed in plaque, calculus, cementum, and dentin obtained from roots of teeth previously exposed to periodontitis. Each fraction was obtained by scaling the root surface. The fraction were extracted by stirring and sonication, and the soluble centrifuged, sterilized, dialyzed, and adjusted to equivalent protein concentrations. Cementum and dentin extracts from impacted teeth were prepared similarly and served as controls. Stimulation of bone resorption by each extract was assessed in organ cultures of fetal rat bones by measurement of release of previously-incorporated 45Ca from the bone into the medium. In some groups of teeth, calculus and cementum were treated with acid prior to scaling. Citric acid washes were recovered and dialyzed. An enzyme-linked immunosorbent assay (ELISA) was used to assess the extracts for the presence of antigens reactive with an antiserum to B. gingivalis. Significant stimulation of bone resorption was found in all calculus and periodontally-involved cementum preparations. ELISA showed significant levels of B.gingivalis antigens in plaque, calculus, and cementum of periodontally-involved teeth, but not in involved dentin nor in cementum or dentin of impact teeth. Treatment with citric acid removed essentially all B.gingivalis antigens from cementum but not calculus. The results suggest that substances which stimulate bone resorption and substances which react with B. gingivalis antiserum are present in surface plaque, calculus, and cementum or periodontally-involved teeth. These substances are not present in cementum and dentin of impacted teeth nor in dentin of periodontally-involved teeth. Treatment by both scaling and citric demineralization will remove most of these substances from cementum of teeth previously exposed to periodontitis. (author)

  3. Bone destruction mechanisms in chronic otitis media with cholesteatoma: specific production by cholesteatoma tissue in culture of bone-resorbing activity attributable to interleukin-1 alpha.

    Science.gov (United States)

    Kurihara, A; Toshima, M; Yuasa, R; Takasaka, T

    1991-12-01

    To clarify specific mechanisms underlying cholesteatoma-induced bone destruction, surgical specimens of middle ear inflammatory granulation tissue with or without cholesteatoma were maintained in vitro and the bone-resorbing activity in their culture supernatants was analyzed by means of calcium release from mouse calvaria. Almost the same levels of bone-resorbing activity and prostaglandin (PG) E2 were found in the supernatants of both types of tissue. By contrast, aural polyp tissue yielded hardly any such activity or PGE2. Under the influence of indomethacin, however, only tissue with cholesteatoma produced considerable bone resorption activity, whereas PGE2 production was suppressed completely. Such activity in the cholesteatoma culture supernatant was not due to contamination of endotoxin and proved to be blocked by the introduction of anti-interleukin (IL)-1 alpha antibody into the calvarial assay system. Anti-IL-1 beta antibody had no effect on such activity. Interleukin-1 alpha was detected only in cholesteatoma tissue culture supernatants by means of enzyme-linked immunosorbent assay and by bioassay. These data suggest that the bone destruction in otitis media with cholesteatoma may be attributed to IL-1 alpha in addition to PGE2. PMID:1746847

  4. Inhibition of miR-21 restores RANKL/OPG ratio in multiple myeloma-derived bone marrow stromal cells and impairs the resorbing activity of mature osteoclasts.

    Science.gov (United States)

    Pitari, Maria Rita; Rossi, Marco; Amodio, Nicola; Botta, Cirino; Morelli, Eugenio; Federico, Cinzia; Gullà, Annamaria; Caracciolo, Daniele; Di Martino, Maria Teresa; Arbitrio, Mariamena; Giordano, Antonio; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2015-09-29

    miR-21 is an oncogenic microRNA (miRNA) with an emerging role as therapeutic target in human malignancies, including multiple myeloma (MM). Here we investigated whether miR-21 is involved in MM-related bone disease (BD). We found that miR-21 expression is dramatically enhanced, while osteoprotegerin (OPG) is strongly reduced, in bone marrow stromal cells (BMSCs) adherent to MM cells. On this basis, we validated the 3'UTR of OPG mRNA as miR-21 target. Constitutive miR-21 inhibition in lentiviral-transduced BMSCs adherent to MM cells restored OPG expression and secretion. Interestingly, miR-21 inhibition reduced RANKL production by BMSCs. Overexpression of protein inhibitor of activated STAT3 (PIAS3), which is a direct and validated target of miR-21, antagonized STAT3-mediated RANKL gene activation. Finally, we demonstrate that constitutive expression of miR-21 inhibitors in BMSCs restores RANKL/OPG balance and dramatically impairs the resorbing activity of mature osteoclasts. Taken together, our data provide proof-of-concept that miR-21 overexpression within MM-microenviroment plays a crucial role in bone resorption/apposition balance, supporting the design of innovative miR-21 inhibition-based strategies for MM-related BD. PMID:26160841

  5. Role of bacterial γ-glutamyltranspeptidase as a novel virulence factor in bone-resorbing pathogenesis.

    Science.gov (United States)

    Kim, Jinmoon; Jang, Sungil; Kim, Aeryun; Su, Hanfu; Gunawardhana, Niluka; Jeon, Yeong-Eui; Bak, Eun Jung; Kim, Ji-Hye; Cha, Jeong-Heon

    2016-05-01

    Mammalian γ-glutamyltranspeptidase (GGT) has been identified as a bone-resorbing factor. Since GGT of Bacillus subtilis exhibits similarity in their primary structure and enzymatic characteristics with mammalian GGTs, the bone-resorbing activity of bacterial GGT was examined in this study. Osteoclastogenesis was performed in a co-culture system of mouse calvaria-derived osteoblasts and bone marrow cells. A conditioned medium from GGT-overproducing B. subtilis culture showed significantly higher activity of osteoclast formation than a conditioned medium from wild-type B. subtilis culture. Recombinant GGT (rGGT) of wild-type B. subtilis and an enzymatic activity-defected rGGT of B. subtilis 2288 mutant were expressed in Escherichia coli and purified using His tag. Both purified rGGTs induced similar levels of osteoclastogenesis, suggesting that B. subtilis GGT possesses virulent bone-resorbing activity and its activity is probably independent of its enzymatic activity. Furthermore, a recombinant protein of B. subtilis GGT heavy subunit (Bs rGGT/H) showed strong activity of osteoclastogenesis while the light subunit failed to show strong activity, suggesting that the bone-resorbing activity is mainly located at the heavy subunit. More importantly, the GGT enzymatic activity may not be required for this virulence activity since the light subunit contains the catalytic pocket. In addition, B. subtilis rGGT stimulated mRNA expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) and cyclooxygenase-2 (COX-2), while an osteoprotegerin inhibited the osteoclast formation induced by Bs rGGT/H. This is the first demonstration that bacterial GGT itself is sufficient to act as a bone-resorbing virulence factor via RANKL-dependent pathway. Therefore, it can be hypothesized that GGT of periodontopathic bacteria may play an important role as a virulence factor in bone destruction. PMID:27095459

  6. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    International Nuclear Information System (INIS)

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method

  7. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian, E-mail: liujianhq@sina.com

    2014-11-01

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.

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

    Directory of Open Access Journals (Sweden)

    Johannes Keller

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

  9. Bone regeneration with resorbable polylactide membrane and sponge in an unstable fracture model in rabbit radius

    OpenAIRE

    Gogolewski, S.; Tsui, K.; Ip, WY

    2003-01-01

    BACKGROUND: Healing of segmental diaphyseal bone defects in animals can be enhanced by covering the defects with resorbable polylactide membranes. Based on the results of bone healing in defects 10 mm long in the rabbit radii, it was suggested that the membranes prevents muscle and soft tissue from invading the defect and maintains osteogenic cells and osteogenic substances within the space covered with membrane, thus promoting new bone formation. OBJECTIVES: 1. To investigate and …

  10. Arthroplasty implant biomaterial particle associated macrophages differentiate into lacunar bone resorbing cells.

    OpenAIRE

    Pandey, R.; Quinn, J.; Joyner, C.; Murray, D W; Triffitt, J T; N. A. Athanasou

    1996-01-01

    OBJECTIVE: To study the pathogenesis of aseptic loosening: in particular, to determine whether macrophages responding to particles of biomaterials commonly used in arthroplasty surgery for arthritis are capable of differentiating into osteoclastic bone resorbing cells, and the cellular and hormonal conditions required for this to occur. METHODS: Biomaterial particles (polymethylmethacrylate, high density polyethylene, titanium, chromium-cobalt, stainless steel) were implanted subcutaneously i...

  11. 21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Prosthetic Devices § 888.3045 Resorbable calcium... are caused by trauma or surgery and are not intrinsic to the stability of the bony structure....

  12. Efficacy of guided bone regeneration using composite bone graft and resorbable collagen membrane in Seibert's Class I ridge defects: radiological evaluation.

    Science.gov (United States)

    Saravanan, Pushparajan; Ramakrishnan, T; Ambalavanan, N; Emmadi, Pamela; John, Thomas Libby

    2013-08-01

    The purpose of the study was to evaluate radiologically the efficacy of guided bone regeneration using composite bone graft (autogenous bone graft and anorganic bovine bone graft [Bio-Oss]) along with resorbable collagen membrane (BioMend Extend) in the augmentation of Seibert's class I ridge defects in maxilla. Bone width was evaluated using computerized tomography at day 0 and at day 180 at 2 mm, 4 mm, and 6 mm from the crest. There was a statistically significant increase in bone width between day 0 and day 180 at 2 mm, 4 mm, and 6 mm from the crest. The results of the study demonstrated an increase in bone width of Seibert's class I ridge defects in the maxilla of the study patients. PMID:23964779

  13. A novel resorbable strontium-containing α-calcium sulfate hemihydrate bone substitute: a preparation and preliminary study

    International Nuclear Information System (INIS)

    Distraction osteogenesis after aggrieved bone segment resections is promising in the treatment of bone tumors and osteomyelitis. However, there is ambiguity with regard to the optimal choice of bone substitute, with biodegradability and excellent bone repair performance constituting key requirements. The purpose of this study was to develop a novel resorbable strontium-containing α-calcium sulfate hemihydrate (Sr-CaS) bone substitute to provide an alternative option for surgeons that better meets these requirements. The Sr-CaS was prepared using co-precipitation and hydrothermal methods and analyzed using x-ray diffraction (XRD), Fourier transform infrared (FTIR) scanning and thermogravimetric differential scanning calorimeter (TG–DSC) patterns. Cytotoxicity by tetrazolium bromide (MTT), sub-acute toxicity and hemolysis tests were performed to assess the initial biocompatibility of the new bone substitute. Radiographic analysis, micro-CT measurements and histological observation were used to evaluate the bone repair ability in rat tibia bone defects. The XRD and FTIR patterns of Sr-CaS were both very similar to CaS and the product had comparable characteristics similar to α-CaS as demonstrated by TG-DSC. Cytotoxicity of the substitute was class 1 (no cytotoxicity) and hemolysis was 4.3% (no hemolysis). Sub-acute toxicity was not seen after a 14 day evaluation. The substitute was radio-opaque. The empty group exhibited the lowest levels of both bone mineral densities (BMD) and bone volume/total volume (BV/TV) of the defects when compared to all other groups. The two Sr-CaS groups resulted in significantly greater BMDs and BV/TV of the defect compared to the CaS only group. However, there was no significant difference between the 5% and 10% Sr-CaS groups. The Sr-CaS was resorbable with satisfactory biocompatibility. The doped strontium ions enhanced the bone repair performance of CaS in a rat model and the new substitute demonstrated promising results for

  14. A novel resorbable strontium-containing α-calcium sulfate hemihydrate bone substitute: a preparation and preliminary study.

    Science.gov (United States)

    Li, Xue; Xu, Chang-peng; Hou, Yi-long; Song, Jin-qi; Cui, Zhuang; Wang, Sheng-nan; Huang, Lei; Zhou, Chang-ren; Yu, Bin

    2014-08-01

    Distraction osteogenesis after aggrieved bone segment resections is promising in the treatment of bone tumors and osteomyelitis. However, there is ambiguity with regard to the optimal choice of bone substitute, with biodegradability and excellent bone repair performance constituting key requirements. The purpose of this study was to develop a novel resorbable strontium-containing α-calcium sulfate hemihydrate (Sr-CaS) bone substitute to provide an alternative option for surgeons that better meets these requirements. The Sr-CaS was prepared using co-precipitation and hydrothermal methods and analyzed using x-ray diffraction (XRD), Fourier transform infrared (FTIR) scanning and thermogravimetric differential scanning calorimeter (TG-DSC) patterns. Cytotoxicity by tetrazolium bromide (MTT), sub-acute toxicity and hemolysis tests were performed to assess the initial biocompatibility of the new bone substitute. Radiographic analysis, micro-CT measurements and histological observation were used to evaluate the bone repair ability in rat tibia bone defects. The XRD and FTIR patterns of Sr-CaS were both very similar to CaS and the product had comparable characteristics similar to α-CaS as demonstrated by TG-DSC. Cytotoxicity of the substitute was class 1 (no cytotoxicity) and hemolysis was 4.3% (no hemolysis). Sub-acute toxicity was not seen after a 14 day evaluation. The substitute was radio-opaque. The empty group exhibited the lowest levels of both bone mineral densities (BMD) and bone volume/total volume (BV/TV) of the defects when compared to all other groups. The two Sr-CaS groups resulted in significantly greater BMDs and BV/TV of the defect compared to the CaS only group. However, there was no significant difference between the 5% and 10% Sr-CaS groups. The Sr-CaS was resorbable with satisfactory biocompatibility. The doped strontium ions enhanced the bone repair performance of CaS in a rat model and the new substitute demonstrated promising results for clinical

  15. Effects of adding resorbable chitosan microspheres to calcium phosphate cements for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Dan [Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050 (China); Dong, Limin [Beijing Key Lab of Fine Ceramics, Institute of Nuclear and New Energy Technology, Tsinghua University, Energy Science Building, Beijing 100084 (China); Wen, Ying [Department of Prosthodontics, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050 (China); Xie, Qiufei, E-mail: xieqiuf@163.com [Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081 (China)

    2015-02-01

    Calcium phosphate cements (CPCs) have been widely used as bone graft substitutes. However, the undesirable osteoinductivity and slow degradability of CPCs greatly hamper their clinical application. The aim of this study was to synthesize a type of injectable, bioactive cement. This was accomplished by incorporating chitosan microspheres into CPC. CPC containing chitosan microspheres was analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM). XRD showed that the hardened chitosan microsphere/CPC with different proportions of microspheres contained diffraction peaks of hydroxyapatite and chitosan. Compressive strength and dissolution in simulated body fluid were measured. The chitosan microsphere/CPC containing 10% (w/w) chitosan microspheres had a compressive strength of 14.78 ± 0.67 MPa. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. Chitosan microsphere/CPC (composite group) and α-TCP/CPC (control group) were implanted separately into the bone defects of both femurs. X-ray analysis was performed to observe the filling of these bone defects 3 days after surgery. The extent of bone substitute degradation and new bone formation were evaluated by SEM and histological examination at 8, 16, and 24 weeks after implantation. These results showed far more new bone formation and degradation of the chitosan microsphere/CPC composite in the bone defects. These data indicate that a chitosan microsphere/CPC composite might be considered as a promising injectable material for the generation of new bone tissue. - Highlights: • We synthesized an injectable, bioactive chitosan microsphere/CPC for the first time. • 100–400 μm chitosan microspheres were incorporated into the cement solid phase. • XRD showed the construct contained diffraction peaks of hydroxyapatite and chitosan. • Compressive strength of the composite was about 15 MPa comparable to cancellous bone. • The new construct shows better bone

  16. Effects of adding resorbable chitosan microspheres to calcium phosphate cements for bone regeneration

    International Nuclear Information System (INIS)

    Calcium phosphate cements (CPCs) have been widely used as bone graft substitutes. However, the undesirable osteoinductivity and slow degradability of CPCs greatly hamper their clinical application. The aim of this study was to synthesize a type of injectable, bioactive cement. This was accomplished by incorporating chitosan microspheres into CPC. CPC containing chitosan microspheres was analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM). XRD showed that the hardened chitosan microsphere/CPC with different proportions of microspheres contained diffraction peaks of hydroxyapatite and chitosan. Compressive strength and dissolution in simulated body fluid were measured. The chitosan microsphere/CPC containing 10% (w/w) chitosan microspheres had a compressive strength of 14.78 ± 0.67 MPa. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. Chitosan microsphere/CPC (composite group) and α-TCP/CPC (control group) were implanted separately into the bone defects of both femurs. X-ray analysis was performed to observe the filling of these bone defects 3 days after surgery. The extent of bone substitute degradation and new bone formation were evaluated by SEM and histological examination at 8, 16, and 24 weeks after implantation. These results showed far more new bone formation and degradation of the chitosan microsphere/CPC composite in the bone defects. These data indicate that a chitosan microsphere/CPC composite might be considered as a promising injectable material for the generation of new bone tissue. - Highlights: • We synthesized an injectable, bioactive chitosan microsphere/CPC for the first time. • 100–400 μm chitosan microspheres were incorporated into the cement solid phase. • XRD showed the construct contained diffraction peaks of hydroxyapatite and chitosan. • Compressive strength of the composite was about 15 MPa comparable to cancellous bone. • The new construct shows better bone

  17. Humoral hypercalcemia of malignancy. Release of a prostaglandin-stimulating bone-resorbing factor in vitro by human transitional-cell carcinoma cells.

    OpenAIRE

    Bringhurst, F R; Bierer, B E; Godeau, F; Neyhard, N; Varner, V; Segre, G. V.

    1986-01-01

    Secretion by tumor cells of circulating bone-resorbing factors may frequently underlie the hypercalcemia that occurs in patients with malignancy. Efforts to identify the responsible mediators have been hampered by a lack of available human tumor cell systems suitable for study of the pathogenesis of the humoral hypercalcemia syndrome. We have established a transitional-cell carcinoma (TCC) line in vitro from a patient with humoral hypercalcemia. These cells are tumorigenic and cause hypercalc...

  18. Resorbable glass-ceramic phosphate-based scaffolds for bone tissue engineering: synthesis, properties, and in vitro effects on human marrow stromal cells.

    Science.gov (United States)

    Vitale-Brovarone, Chiara; Ciapetti, Gabriela; Leonardi, Elisa; Baldini, Nicola; Bretcanu, Oana; Verné, Enrica; Baino, Francesco

    2011-11-01

    Highly porous bioresorbable glass-ceramic scaffolds were prepared via sponge replication method by using an open-cell polyurethane foam as a template and phosphate-based glass powders. The glass, belonging to the P2O5-SiO2-CaO-MgO-Na2O-K2O system, was synthesized by a melting-quenching route, ground, and sieved to obtain powders with a grain size of less than 30 μm. A slurry containing glass powders, polyvinyl alcohol, and water was prepared to coat the polymeric template. The removal of the polymer and the sintering of the glass powders were performed by a thermal treatment, in order to obtain an inorganic replica of the template structure. The structure and properties of the scaffold were investigated from structural, morphological, and mechanical viewpoints by means of X-ray diffraction, scanning electron microscopy, density measurements, image analysis, and compressive tests. The scaffolds exhibited a trabecular architecture that closely mimics the structure of a natural spongy bone. The solubility of the porous structures was assessed by soaking the samples in acellular simulated body fluid (SBF) and Tris-HCl for different time frames and then by assessing the scaffold weight loss. As far as the test in SBF is concerned, the nucleation of hydroxyapatite on the scaffold trabeculae demonstrates the bioactivity of the material. Biological tests were carried out using human bone marrow stromal cells to test the osteoconductivity of the material. The cells adhered to the scaffold struts and were metabolically active; it was found that cell differentiation over proliferation occurred. Therefore, the produced scaffolds, being biocompatible, bioactive, resorbable, and structurally similar to a spongy bone, can be proposed as interesting candidates for bone grafting. PMID:20566654

  19. Effect of interferon-γ on the fusion of mononuclear osteoclasts into bone-resorbing osteoclasts

    Directory of Open Access Journals (Sweden)

    Jeung Woo Kim

    2012-05-01

    Full Text Available Osteoclasts are multinucleated cells that are formed by the fusionof pre-fusion osteoclasts (pOCs. The fusion of pOCs isknown to be important for osteoclastic bone resorption. Here,we examined the effect of IFN-γ on the fusion of pOCs. IFN-γgreatly increased the fusion of pOCs in a dose-dependentmanner. Furthermore, IFN-γ induced pOC fusion even in hydroxyapatite-coated plates used as a substitute for bone. Theresorption area of pOCs stimulated with IFN-γ was significantlyhigher than that of the control cells. IFN-γ induced theexpression of dendritic cell-specific transmembrane protein(DC-STAMP, which is responsible for the fusion of pOCs.IFN-γ enhanced DC-STAMP expression in a dose-dependentmanner. The mRNA expression of c-Fos and nuclear factor ofactivated T cells (NFAT c1 was enhanced in the pOCs treatedwith IFN-γ. Taken together, these results provide a new insightinto the novel role of IFN-γ on the fusion of pOCs. [BMB reports2012; 45(5: 281-286

  20. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: An In Vivo Microcomputed Tomographic Analysis.

    Science.gov (United States)

    Babay, Nadir; Ramalingam, Sundar; Basudan, Amani; Nooh, Nasser; AlKindi, Mohammed; Al-Rasheed, Abdulaziz; Al-Hezaimi, Khalid

    2016-01-01

    The aim of this in vivo microcomputed tomographic (μCT) study was to compare the efficacy of Mucograft (MG) vs resorbable collagen membranes (RCMs) in facilitating guided bone regeneration (GBR) around standardized calvarial defects in rats. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A standardized calvarial defect with a 4.6-mm diameter was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) defects covered with MG (MG group); (2) defects covered with an RCM (RCM group); (3) defects filled with xenograft bone particles and covered by MG (MG + bone group); and (4) defects filled with xenograft bone particles and covered by an RCM (RCM + bone group). Primary closure was achieved using interrupted resorbable sutures. The animals underwent high-resolution, three-dimensional μCT scans at baseline and at 2, 4, 6, and 8 weeks after the surgical procedures. Data regarding volume and bone mineral density (BMD) of newly formed bone (NFB) and bone particles revealed an increase in the volume of NFB in all the groups from baseline to 8 weeks. The MG group had the lowest volume of NFB (mean ± standard deviation [SD], 1.32 ± 0.22 mm(3)). No significant differences in mean ± SD values for volume of NFB were observed between the RCM (3.50 ± 0.24 mm(3)) and MG + bone (3.87 ± 0.36 mm(3)) groups, but their values were significantly lower than that of the RCM + bone group (2.95 ± 0.15 mm(3), F = 131.91, dfN = 2, dfD = 27, P RCM group having the highest mean ± SD BMD of NFB (0.42 ± 0.05 g/mm(3)). Significant differences in the bone particle volume between the RCM + bone and MG + bone groups (F = 91.04, dfN = 1, dfD = 18, P RCM + bone group displaying greater reduction in both volume (36.8%) and BMD (19.7%) of bone particles

  1. Efficacy of Mucograft vs Conventional Resorbable Collagen Membranes in Guided Bone Regeneration Around Standardized Calvarial Defects in Rats: A Histologic and Biomechanical Assessment.

    Science.gov (United States)

    Ramalingam, Sundar; Babay, Nadir; Al-Rasheed, Abdulaziz; Nooh, Nasser; Naghshbandi, Jafar; Aldahmash, Abdullah; Atteya, Muhammad; Al-Hezaimi, Khalid

    2016-01-01

    Guided bone regeneration (GBR) using a porcine-derived collagen matrix (Mucograft [MG], Geistlich) has not yet been reported. The aim of this histologic and biomechanical study was to compare the efficacy of MG versus resorbable collagen membranes (RCMs) in facilitating GBR around standardized rat calvarial defects. Forty female Wistar albino rats with a mean age and weight of 6 to 9 weeks and 250 to 300 g, respectively, were used. With the rats under general anesthesia, the skin over the calvaria was exposed using a full-thickness flap. A 4.6-mm-diameter standardized calvarial defect was created in the left parietal bone. For treatment, the rats were randomly divided into four groups (n = 10 per group): (1) MG group: the defect was covered with MG; (2) RCM group: the defect was covered with an RCM; (3) MG + bone group: the defect was filled with bone graft particles and covered by MG; and (4) RCM + bone group: the defect was filled with bone graft particles and covered by an RCM. Primary closure was achieved using interrupted resorbable sutures. The animals were sacrificed at 8 weeks after the surgical procedures. Qualitative histologic analysis and biomechanical assessment to identify hardness and elastic modulus of newly formed bone (NFB) were performed. Collected data were statistically analyzed using one-way analysis of variance. Histologic findings revealed NFB with fibrous connective tissue in all groups. The quantity of NFB was highest in the RCM + bone group. Statistically significant differences in the hardness (F = 567.69, dfN = 3, dfD = 36, P RCM + bone group had the highest mean ± standard deviation (SD) hardness of NFB (531.4 ± 24.9 MPa), the RCM group had the highest mean ± SD elastic modulus of NFB (18.63 ± 1.89 GPa). The present study demonstrated that RCMs are better than MG at enhancing new bone formation in standardized rat calvarial defects when used along with mineralized particulate graft material. PMID:27031638

  2. Deoxyactein stimulates osteoblast function and inhibits bone-resorbing mediators in MC3T3-E1 cells.

    Science.gov (United States)

    Choi, Eun Mi

    2013-03-01

    Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In order to improve the treatment of osteoporosis, identification of anabolic agents with minimal side effects is highly desirable. Cimicifuga racemosa has a long and diverse history of medicinal use and deoxyactein isolated from this species is one of the major constituents. In the present study, the effect of deoxyactein on the function of osteoblastic MC3T3-E1 cells was studied. Deoxyactein caused a significant elevation of cell growth, alkaline phosphatase activity, collagen content, and mineralization in the cells (P < 0.05). Moreover, deoxyactein significantly (P < 0.05) decreased the production of reactive oxygen species (ROS) and osteoclast differentiation-inducing factors such as TNF-α, IL-6 and receptor activator of nuclear factor-κB ligand in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as an ROS generator. These results demonstrate that deoxyactein may have positive effects on skeletal structure. PMID:21910134

  3. Pleiotropic activity of lysophosphatidic acid in bone metastasis.

    Science.gov (United States)

    Peyruchaud, Olivier; Leblanc, Raphael; David, Marion

    2013-01-01

    Bone is a common metastatic site for solid cancers. Bone homeostasis is tightly regulated by intimate cross-talks between osteoblast (bone forming cells) and osteoclasts (bone resorbing cells). Once in the bone microenvironment, metastatic cells do not alter bone directly but instead perturb the physiological balance of the bone remodeling process controlled by bone cells. Tumor cells produce growth factors and cytokines stimulating either osteoclast activity leading to osteolytic lesions or osteoblast function resulting in osteoblastic metastases. Growth factors, released from the resorbed bone matrix or throughout osteoblastic bone formation, sustain tumor growth. Therefore, bone metastases are the sites of vicious cycles wherein tumor growth and bone metabolism sustain each other. Lysophosphatidic acid (LPA) promotes the growth of primary tumors and metastatic dissemination of cancer cells. We have shown that by acting on cancer cells via the contribution of blood platelets and the LPA-producing enzyme Autotaxin (ATX), LPA promotes the progression of osteolytic bone metastases in animal models. In the light of recent reports it would appear that the role of LPA in the context of bone metastases is complex involving multiple sources of lipid combined with direct and indirect effects on target cells. This review will present our current knowledge on the LPA/ATX axis involvement in osteolytic and osteoblastic skeletal metastases and will discuss the potential activity of LPA upstream and downstream metastasis seeding of cancer cells to bone as well as its implication in cancer induced bone pain. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. PMID:22710393

  4. Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue

    OpenAIRE

    Cardoso, Luis; Herman, Brad C.; Verborgt, Olivier; Laudier, Damien; Majeska, Robert J.; Schaffler, Mitchell B.

    2008-01-01

    Osteocyte apoptosis is spatially and temporally linked to bone fatigue–induced microdamage and to subsequent intracortical remodeling. Specifically, osteocytes surrounding fatigue microcracks in bone undergo apoptosis, and those regions containing apoptotic osteocytes co-localize exactly with areas subsequently resorbed by osteoclasts. Here we tested the hypothesis that osteocyte apoptosis is a key controlling step in the activation and/or targeting of osteoclastic resorption after bone fatig...

  5. Efficacy of combination therapy using anorganic bovine bone graft with resorbable GTR membrane vs. open flap debridement alone in the management of grade II furcation defects in mandibular molars – A comparative study

    OpenAIRE

    Kannan, Anitha Logaranjani; Bose, Buvaneshwari Birla; Muthu, Jananni; Perumalsamy, Rajapriya; Pushparajan, Saravanan; Namasivayam, Ambalavanan

    2014-01-01

    Context: Invasion of the bifurcation and trifurcation of the multi-rooted teeth resulting in furcation involvement is one of the serious complications of periodontitis. Aim: The purpose of the study was to evaluate the efficacy of combination therapy using anorganic bovine bone graft and resorbable guided tissue regeneration (GTR) membrane versus open flap debridement alone in the management of Grade II furcation defects in mandibular molars. Materials and Methods: The study included a total ...

  6. Bone healing after low-level laser application in extraction sockets grafted with allograft material and covered with a resorbable collagen dressing: a pilot histological evaluation

    OpenAIRE

    Monea, Adriana; Beresescu, Gabriela; Tibor, Mezei; Popsor, Sorin; Antonescu, Dragos Mihai

    2015-01-01

    Background Our aim was to determine whether low level laser therapy (LLLT) can decrease the time between extraction/socket graft and implant placement, by evaluating histological changes in sockets grafted with a particulate allograft material and treated with LLLT. Methods Thirty patients had a socket grafted with a particulate allograft material (MinerOss) covered with a resorbable collagen wound dressing. The patients were then randomly divided into two equal groups (n = 15): test group re...

  7. Assessment of Bonelike (registered) graft with a resorbable matrix using an animal model

    International Nuclear Information System (INIS)

    Synthetic bone grafts have been developed to provide an alternative to autografts and allografts. Bonelike (registered) is a patented synthetic osteoconductive bone graft that mimics the mineral composition of natural bone. In the present preliminary animal studies a user-friendly version of synthetic bone graft Bonelike (registered) have been developed by using a resorbable matrix, Floseal (registered) , as a vehicle and raloxifene hydrochloride as a therapeutic molecule, that is known to decrease osteoclast activity and therefore enhanced bone formation. From histological and scanning electron microscopy evaluations, the use of Bonelike (registered) associated with Floseal (registered) and raloxifene hydrochloride showed that new bone was rapidly apposed on implanted granules and also that the presence of the matrix and therapeutic molecule does not alter the proven highly osteoconductivity properties of Bonelike (registered) . Therefore, this association may be one step-forward for the clinical applications of Bonelike (registered) scaffolds since it is much more easy-to-handle when compared to granular materials

  8. Assessment of Bonelike (registered) graft with a resorbable matrix using an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, J.V. [CHVNG-Servico de Estomatologia, Centro Hospitalar de Vila Nova de Gaia (Portugal); ICBAS-Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto (Portugal); CECA/ICETA-Centro de Estudos de Ciencia Animal, Instituto de Ciencias e Tecnologias Agrarias e Agro-Alimentares, Campus Agrario de Vairao, Rua Padre Armando Quintas, 4485-661 Vairao (Portugal); Hussain, N. Sooraj [INEB-Instituto de Engenharia Biomedica, Laboratorio de Biomateriais, Rua Campo Alegre, 823, 4150-180, Porto (Portugal); FEUP-Faculdade de Engenharia da Universidade do Porto, DEMM, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Botelho, C.M. [INEB-Instituto de Engenharia Biomedica, Laboratorio de Biomateriais, Rua Campo Alegre, 823, 4150-180, Porto (Portugal); FEUP-Faculdade de Engenharia da Universidade do Porto, DEMM, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Mauricio, A.C. [ICBAS-Instituto de Ciencias Biomedicas de Abel Salazar, Universidade do Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto (Portugal); CECA/ICETA-Centro de Estudos de Ciencia Animal, Instituto de Ciencias e Tecnologias Agrarias e Agro-Alimentares, Campus Agrario de Vairao, Rua Padre Armando Quintas, 4485-661 Vairao (Portugal); Afonso, A. [FMDUP-Faculdade de Medicina Dentaria da Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto (Portugal); Ali, N. [Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Santos, J.D. [INEB-Instituto de Engenharia Biomedica, Laboratorio de Biomateriais, Rua Campo Alegre, 823, 4150-180, Porto (Portugal) and FEUP-Faculdade de Engenharia da Universidade do Porto, DEMM, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal)]. E-mail: jdsantos@fe.up.pt

    2006-09-25

    Synthetic bone grafts have been developed to provide an alternative to autografts and allografts. Bonelike (registered) is a patented synthetic osteoconductive bone graft that mimics the mineral composition of natural bone. In the present preliminary animal studies a user-friendly version of synthetic bone graft Bonelike (registered) have been developed by using a resorbable matrix, Floseal (registered) , as a vehicle and raloxifene hydrochloride as a therapeutic molecule, that is known to decrease osteoclast activity and therefore enhanced bone formation. From histological and scanning electron microscopy evaluations, the use of Bonelike (registered) associated with Floseal (registered) and raloxifene hydrochloride showed that new bone was rapidly apposed on implanted granules and also that the presence of the matrix and therapeutic molecule does not alter the proven highly osteoconductivity properties of Bonelike (registered) . Therefore, this association may be one step-forward for the clinical applications of Bonelike (registered) scaffolds since it is much more easy-to-handle when compared to granular materials.

  9. Efficacy of combination therapy using anorganic bovine bone graft with resorbable GTR membrane vs. open flap debridement alone in the management of grade II furcation defects in mandibular molars – A comparative study

    Science.gov (United States)

    Kannan, Anitha Logaranjani; Bose, Buvaneshwari Birla; Muthu, Jananni; Perumalsamy, Rajapriya; Pushparajan, Saravanan; Namasivayam, Ambalavanan

    2014-01-01

    Context: Invasion of the bifurcation and trifurcation of the multi-rooted teeth resulting in furcation involvement is one of the serious complications of periodontitis. Aim: The purpose of the study was to evaluate the efficacy of combination therapy using anorganic bovine bone graft and resorbable guided tissue regeneration (GTR) membrane versus open flap debridement alone in the management of Grade II furcation defects in mandibular molars. Materials and Methods: The study included a total number of 20 sites in 10 patients with bilateral mandibular furcation defects, out of which 10 sites were treated as test group and 10 as control group. The test group was treated with combination therapy and the control group with open flap debridement alone. The parameters were recorded on 0 day (baseline), 90th day, and 180th day, which included vertical probing depth and horizontal probing depth of the furcation defect, clinical attachment level, and defect fill. Statistical Analysis Used: Mean and standard deviation were calculated for different variables in each study group at different time points. Mean values were compared by using Wilcoxon signed ranks test, after adjusting the P values for multiple comparison by using Bonferroni correction method. Results: Both the test and control groups showed a definitive improvement in clinical parameters, which was statistically significant. On comparison, the vertical probing depth showed significant reduction in the test group with a mean reduction of 3.1 ± 0.7 mm, when compared to the control group which showed a mean reduction of 1.5 ± 0.5 mm. The horizontal probing depth of furcation defects was also significantly reduced in the test group with a mean reduction of 2.2 ± 0.6 mm, when compared to the control group in which the mean reduction was 0.9 ± 0.3 mm. There was also significant gain in attachment level in the test group which showed a mean gain of 3.2 ± 0.6 mm, when compared to the control group which showed a

  10. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  11. Reduction of instability-induced bone resorption using bisphosphonates: high doses are needed in rats.

    OpenAIRE

    Åstrand, Jörgen; Aspenberg, Per

    2002-01-01

    Bone resorption associated with prosthetic loosening can be reduced by giving bisphosphonates since they bind to bone surfaces and inactivate osteoclasts when bisphosphonate-containing bone is resorbed. During loosening, an increase in osteoclastic activity can be triggered by mechanical instability, fluid pressure or wear particles. We used a rat model in which a titanium surface can be made to slide over a bone surface and cause instability-induced bone resorption. 111 rats were operated on...

  12. Distinctive subdomains in the resorbing surface of osteoclasts.

    Directory of Open Access Journals (Sweden)

    Kinga A Szewczyk

    Full Text Available We employed a novel technique to inspect the substrate-apposed surface of activated osteoclasts, the cells that resorb bone, in the scanning electron microscope. The surface revealed unexpected complexity. At the periphery of the cells were circles and crescents of individual or confluent nodules. These corresponded to the podosomes and actin rings that form a 'sealing zone', encircling the resorptive hemivacuole into which protons and enzymes are secreted. Inside these rings and crescents the osteoclast surface was covered with strips and patches of membrane folds, which were flattened against the substrate surface and surrounded by fold-free membrane in which many orifices could be seen. Corresponding regions of folded and fold-free membrane were found by transmission electron microscopy in osteoclasts incubated on bone. We correlated these patterns with the distribution of several proteins crucial to resorption. The strips and patches of membrane folds corresponded in distribution to vacuolar H+-ATPase, and frequently co-localized with F-actin. Cathepsin K localized to F-actin-free foci towards the center of cells with circular actin rings, and at the retreating pole of cells with actin crescents. The chloride/proton antiporter ClC-7 formed a sharply-defined band immediately inside the actin ring, peripheral to vacuolar H+-ATPase. The sealing zone of osteoclasts is permeable to molecules with molecular mass up to 10,000. Therefore, ClC-7 might be distributed at the periphery of the resorptive hemivacuole in order to prevent protons from escaping laterally from the hemivacuole into the sealing zone, where they would dissolve the bone mineral. Since the activation of resorption is attributable to recognition of the αVβ3 ligands bound to bone mineral, such leakage would, by dissolving bone mineral, release the ligands and so terminate resorption. Therefore, ClC-7 might serve not only to provide the counter-ions that enable proton pumping, but

  13. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  14. Thrombospondin-1 regulates bone homeostasis through effects on bone matrix integrity and nitric oxide signaling in osteoclasts

    OpenAIRE

    Sarah R Amend; Uluckan, Ozge; Hurchla, Michelle; Leib, Daniel; Novack, Deborah Veis; Silva, Matthew; Frazier, William; Weilbaecher, Katherine N.

    2015-01-01

    Thrombospondin-1 (TSP1), an endogenous antiangiogenic, is a widely expressed secreted ligand with roles in migration, adhesion and proliferation and is a target for new therapeutics. While TSP1 is present in the bone matrix and several TSP1 receptors play roles in bone biology, the role of TSP1 in bone remodeling has not been fully elucidated. Bone turnover is characterized by coordinated activity of bone-forming osteoblasts (OB) and bone-resorbing osteoclasts (OC). TSP1−/− mice had increased...

  15. Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings

    OpenAIRE

    Kim, Jinku; Magno, Maria Hanshella R.; Ortiz, Ophir; McBride, Sean; Darr, Aniq; Kohn, Joachim; Hollinger, Jeffrey O.

    2015-01-01

    Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components. In this article, we continue our exploration of E1001(1k), a tyrosine-derived polycarbonate, as an orthopedic implant material. Specifically, we use E1001(1k), which is degradable, nontoxic, and osteoconductive, to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate (CP) coatings: in one case, pure ...

  16. The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts.

    Science.gov (United States)

    Thirukonda, Gnanasagar J; Uehara, Shunsuke; Nakayama, Takahiro; Yamashita, Teruhito; Nakamura, Yukio; Mizoguchi, Toshihide; Takahashi, Naoyuki; Yagami, Kimitoshi; Udagawa, Nobuyuki; Kobayashi, Yasuhiro

    2016-07-01

    The cytoskeletal organization of osteoclasts is required for bone resorption. Binding of dynamin with guanosine triphosphate (GTP) was previously suggested to be required for the organization of the actin cytoskeleton. However, the role of the GTPase activity of dynamin in the organization of the actin cytoskeleton as well as in the bone-resorbing activity of osteoclasts remains unclear. This study investigated the effects of dynasore, an inhibitor of the GTPase activity of dynamin, on the bone-resorbing activity of and actin ring formation in mouse osteoclasts in vitro and in vivo. Dynasore inhibited the formation of resorption pits in osteoclast cultures by suppressing actin ring formation and rapidly disrupting actin rings in osteoclasts. A time-lapse image analysis showed that dynasore shrank actin rings in osteoclasts within 30 min. The intraperitoneal administration of dynasore inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced trabecular bone loss in mouse femurs. These in vitro and in vivo results suggest that the GTPase activity of dynamin is critical for the bone-resorbing activity of osteoclasts and that dynasore is a seed for the development of novel anti-resorbing agents. PMID:26063501

  17. Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro

    DEFF Research Database (Denmark)

    Feng, Shan; Madsen, Suzi H; Viller, Natasja N;

    2015-01-01

    Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer (NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow...

  18. Implantology and the severely resorbed edentulous mandible

    OpenAIRE

    Stellingsma, C.; Vissink, A; Meijer, H.J.A.; Raghoebar, G.M.

    2004-01-01

    Patients with a severely resorbed edentulous mandible often suffer from problems with the lower denture. These problems include: insufficient retention of the lower denture, intolerance to loading by the mucosa, pain, difficulties with eating and speech, loss of soft-tissue support, and altered facial appearance. These problems are a challenge for the prosthodontist and surgeon. Dental implants have been shown to provide a reliable basis for fixed and removable prostheses. This has resulted i...

  19. Active Bone Conduction Prosthesis: BonebridgeTM

    Science.gov (United States)

    Zernotti, Mario E.; Sarasty, Andrea Bravo

    2015-01-01

    Introduction Bone conduction implants are indicated for patients with conductive and mixed hearing loss, as well as for patients with single-sided deafness (SSD). The transcutaneous technology avoids several complications of the percutaneous bone conduction implants including skin reaction, skin growth over the abutment, and wound infection. The Bonebridge (MED-EL, Austria) prosthesis is a semi-implantable hearing system: the BCI (Bone Conduction Implant) is the implantable part that contains the Bone Conduction-Floating Mass Transducer (BC-FMT), which applies the vibrations directly to the bone; the external component is the audio processor Amadé BB (MED-EL, Austria), which digitally processes the sound and sends the information through the coil to the internal part. Bonebridge may be implanted through three different approaches: the transmastoid, the retrosigmoid, or the middle fossa approach. Objective This systematic review aims to describe the world́s first active bone conduction implant system, Bonebridge, as well as describe the surgical techniques in the three possible approaches, showing results from implant centers in the world in terms of functional gain, speech reception thresholds and word recognition scores. Data Synthesis The authors searched the MEDLINE database using the key term Bonebridge. They selected only five publications to include in this systematic review. The review analyzes 20 patients that received Bonebridge implants with different approaches and pathologies. Conclusion Bonebridge is a solution for patients with conductive/mixed hearing loss and SSD with different surgical approaches, depending on their anatomy. The system imparts fewer complications than percutaneous bone conduction implants and shows proven benefits in speech discrimination and functional gain. PMID:26491482

  20. Active Bone Conduction Prosthesis: Bonebridge(TM).

    Science.gov (United States)

    Zernotti, Mario E; Sarasty, Andrea Bravo

    2015-10-01

    Introduction Bone conduction implants are indicated for patients with conductive and mixed hearing loss, as well as for patients with single-sided deafness (SSD). The transcutaneous technology avoids several complications of the percutaneous bone conduction implants including skin reaction, skin growth over the abutment, and wound infection. The Bonebridge (MED-EL, Austria) prosthesis is a semi-implantable hearing system: the BCI (Bone Conduction Implant) is the implantable part that contains the Bone Conduction-Floating Mass Transducer (BC-FMT), which applies the vibrations directly to the bone; the external component is the audio processor Amadé BB (MED-EL, Austria), which digitally processes the sound and sends the information through the coil to the internal part. Bonebridge may be implanted through three different approaches: the transmastoid, the retrosigmoid, or the middle fossa approach. Objective This systematic review aims to describe the world́s first active bone conduction implant system, Bonebridge, as well as describe the surgical techniques in the three possible approaches, showing results from implant centers in the world in terms of functional gain, speech reception thresholds and word recognition scores. Data Synthesis The authors searched the MEDLINE database using the key term Bonebridge. They selected only five publications to include in this systematic review. The review analyzes 20 patients that received Bonebridge implants with different approaches and pathologies. Conclusion Bonebridge is a solution for patients with conductive/mixed hearing loss and SSD with different surgical approaches, depending on their anatomy. The system imparts fewer complications than percutaneous bone conduction implants and shows proven benefits in speech discrimination and functional gain. PMID:26491482

  1. BONE TUMOR ENVIRONMENT AS POTENTIAL THERAPEUTIC TARGET IN EWING SARCOMA

    Directory of Open Access Journals (Sweden)

    Françoise eREDINI

    2015-12-01

    Full Text Available Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, ES is an aggressive, rapidly fatal malignancy that mainly develops in osseous sites (85%, but also in extraskeletal soft tissue. It spreads naturally to the lungs, bones and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption is responsible for the clinical features of bone tumors including pain, vertebral collapse and spinal cord compression. Based on the vicious cycle concept of tumor cells and bone resorbing cells, drugs which target osteoclasts may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable niche for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing Sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates (BPs or drugs blocking the pro-resorbing cytokine Receptor Activator of NF-kappa B Ligand (RANKL. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

  2. Guided Cartilege Regeneration Using Resorbable Template

    Directory of Open Access Journals (Sweden)

    Pomahac, Bohdan

    Full Text Available Objective: The reconstruction of a defect involving complex cartilaginous structures such as the ear and nose is a difficult problem. Cartilage donor sites are limited, and the shaping of an ear or nose is dependent upon the surgeon's skills and experience. In this report, we propose to use resorbable plates that can be shaped to serve as a template for cartilage healing. Methods: A shell omposed of polylactic/polyglycolic acid copolymer sheet was molded into different shapes. Autologous ribs harvested from 2 New Zealand rabbits were slightly crushed and bent without breaking, and placed within the pre-shaped shell. The constructs were implanted into subcutaneous pockets in the flanks of the rabbits. After 8 weeks, the implanted cartilage constructs were taken out of the shell and analyzed by the gross macroscopic appearance for preservation of the shape and by histological means for analysis of cartilage viability. Results: All of the explanted cartilage constructs retained the same pre-implanted shape and contour. Upon histological examination with hematoxylin/eosin staining, the constructs were composed of a continuous layer of viable chondrocytes. Conclusions: Construction of complex cartilaginous structures is an operator-dependent, technically difficult problem. We propose to use a resorbable template for guiding the shape and healing of the desired cartilaginous construct. Preoperative scanning and precise 3-dimensional shaping of the template could achieve further improvement in the desired cartilaginous support of the reconstructed part. In this report, we document that cartilage enclosed in a resorbable template retains its shape and viability. We believe that a prefabricated shell may help simplify and standardize outcomes of ear or nose reconstruction.

  3. Similar healthy osteoclast and osteoblast activity on nanocrystalline hydroxyapatite and nanoparticles of tri-calcium phosphate compared to natural bone

    Directory of Open Access Journals (Sweden)

    MacMillan AK

    2014-12-01

    Full Text Available Adam K MacMillan,1 Francis V Lamberti,1 Julia N Moulton,2 Benjamin M Geilich,2 Thomas J Webster2,3 1RTI Surgical, Alachua, FL, USA; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: While there have been numerous studies to determine osteoblast (bone forming cell functions on nanocrystalline compared to micron crystalline ceramics, there have been few studies which have examined osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and receptor activator of nuclear factor κB [RANK]. This is despite the fact that osteoclasts are an important part of maintaining healthy bone since they resorb bone during the bone remodeling process. Moreover, while it is now well documented that bone formation is enhanced on nanoceramics compared to micron ceramics, some have pondered whether osteoblast functions (such as osteoprotegerin and RANK ligand [RANKL] are normal (ie, non-diseased on such materials compared to natural bone. For these reasons, the objective of the present in vitro study was to determine various functions of osteoclasts and osteoblasts on nanocrystalline and micron crystalline hydroxyapatite as well as tri-calcium phosphate materials and compare such results to cortical and cancellous bone. Results showed for the first time similar osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and RANK and osteoblast activity (osteoprotegerin and RANKL on nanocrystalline hydroxyapatite compared to natural bone, whereas osteoclast and osteoblast functions on micron crystalline versions of these ceramics were much different than natural bone. In this manner, this study provides additional evidence that nanocrystalline calcium phosphates can serve as suitable synthetic

  4. Recombinant VSV G proteins reveal a novel raft-dependent endocytic pathway in resorbing osteoclasts

    International Nuclear Information System (INIS)

    Transcytotic membrane flow delivers degraded bone fragments from the ruffled border to the functional secretory domain, FSD, in bone resorbing osteoclasts. Here we show that there is also a FSD-to-ruffled border trafficking pathway that compensates for the membrane loss during the matrix uptake process and that rafts are essential for this ruffled border-targeted endosomal pathway. Replacing the cytoplasmic tail of the vesicular stomatitis virus G protein with that of CD4 resulted in partial insolubility in Triton X-100 and retargeting from the peripheral non-bone facing plasma membrane to the FSD. Recombinant G proteins were subsequently endosytosed and delivered from the FSD to the peripheral fusion zone of the ruffled border, which were both rich in lipid rafts as suggested by viral protein transport analysis and visualizing the rafts with fluorescent recombinant cholera toxin. Cholesterol depletion by methyl-β-cyclodextrin impaired the ruffled border-targeted vesicle trafficking pathway and inhibited bone resorption dose-dependently as quantified by measuring the CTX and TRACP 5b secreted to the culture medium and by measuring the resorbed area visualized with a bi-phasic labeling method using sulpho-NHS-biotin and WGA-lectin. Thus, rafts are vital for membrane recycling from the FSD to the late endosomal/lysosomal ruffled border and bone resorption

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

    Science.gov (United States)

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

    2010-08-01

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

  6. A novel one-pot process for near-net-shape fabrication of open-porous resorbable hydroxyapatite/protein composites and in vivo assessment

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Berit, E-mail: beritm@uni-bremen.de [University of Bremen, Advanced Ceramics, Am Biologischen Garten 2, 28359 Bremen (Germany); Koch, Dietmar, E-mail: dietmar.koch@dlr.de [German Aerospace Center, Ceramic Composite Structures, Pfaffenwaldring 38-40, 70569 Stuttgart (Germany); Lutz, Rainer, E-mail: rainer.lutz@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Oral and Maxillofacial Surgery, Glueckstrasse 11, 91054 Erlangen (Germany); Schlegel, Karl A., E-mail: andreas.schlegel@uk-erlangen.de [University of Erlangen-Nuremberg, Department of Oral and Maxillofacial Surgery, Glueckstrasse 11, 91054 Erlangen (Germany); Treccani, Laura, E-mail: treccani@uni-bremen.de [University of Bremen, Advanced Ceramics, Am Biologischen Garten 2, 28359 Bremen (Germany); Rezwan, Kurosch, E-mail: krezwan@uni-bremen.de [University of Bremen, Advanced Ceramics, Am Biologischen Garten 2, 28359 Bremen (Germany)

    2014-09-01

    We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery. - Highlights: • We present a one-pot process for directly incorporating protein into HAp scaffolds. • The effect of two model proteins, BSA and LSZ, on scaffold properties is analysed. • HAp/protein scaffolds feature a mechanical strength comparable to human spongiosa. • BSA incorporation in scaffolds leads to strength increase despite porosity increment. • New bone formation in-vivo exceeds established xenograft bone substitutes.

  7. A novel one-pot process for near-net-shape fabrication of open-porous resorbable hydroxyapatite/protein composites and in vivo assessment

    International Nuclear Information System (INIS)

    We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery. - Highlights: • We present a one-pot process for directly incorporating protein into HAp scaffolds. • The effect of two model proteins, BSA and LSZ, on scaffold properties is analysed. • HAp/protein scaffolds feature a mechanical strength comparable to human spongiosa. • BSA incorporation in scaffolds leads to strength increase despite porosity increment. • New bone formation in-vivo exceeds established xenograft bone substitutes

  8. Assessing bone banking activities at University of Malaya medical centre.

    Science.gov (United States)

    Mohd, Suhaili; Samsuddin, Sharifah Mazni; Ramalingam, Saravana; Min, Ng Wuey; Yusof, Norimah; Zaman, T Kamarul; Mansor, Azura

    2015-12-01

    The main advantage of establishing in-house bone banks is its ability to readily provide allograft bones for local surgeries. Bone procurement activities of our university bone bank during the 10 years of operation were reviewed. Socio-demographic data of donors, types of bone procured, cases of rejected bones and types of allograft bones transplanted are presented. From 179 potential donors, 73 % were accepted with 213 procured bones. Femoral head was the common bone transplanted (45 %), as it was also the most common procured (82 %). Bones were rejected mainly due to non-technical reasons (83 %) rather than positive results of microbiological (13 %) and serological (4 %) tests. Comprehensive data could not be obtained for further analysis due to difficulties in retrieving information. Therefore, quality assurance system was improved to establish more systematic documentations, as the basis of good banking practice with process control hence allowing traceability. PMID:25656787

  9. Physical activity increases bone mass during growth

    OpenAIRE

    Karlsson, Magnus K; Nordvist, Anders; Karlsson, Caroline

    2008-01-01

    Background: The incidence of fragility fractures has increased during the last half of the 1900?s. One important determinant of fractures is the bone mineral content (BMC) or bone mineral density (BMD), the amount of mineralised bone. If we could increase peak bone mass (the highest value of BMC reached during life) and/or decrease the age-related bone loss, we could possibly improve the skeletal resistance to fracture. Objective: This review evaluates the importance of exercise as a strategy...

  10. The turnover of mineralized growth plate cartilage into bone may be regulated by osteocytes.

    Science.gov (United States)

    Cox, Lieke G E; van Rietbergen, B; van Donkelaar, C C; Ito, K

    2011-06-01

    During endochondral ossification, growth plate cartilage is replaced with bone. Mineralized cartilage matrix is resorbed by osteoclasts, and new bone tissue is formed by osteoblasts. As mineralized cartilage does not contain any cells, it is unclear how this process is regulated. We hypothesize that, in analogy with bone remodeling, osteoclast and osteoblast activity are regulated by osteocytes, in response to mechanical loading. Since the cartilage does not contain osteocytes, this means that cartilage turnover during endochondral ossification would be regulated by the adjacent bone tissue. We investigated this hypothesis with an established computational bone adaptation model. In this model, osteocytes stimulate osteoblastic bone formation in response to the mechanical bone tissue loading. Osteoclasts resorb bone near randomly occurring microcracks that are assumed to block osteocyte signals. We used finite element modeling to evaluate our hypothesis in a 2D-domain representing part of the growth plate and adjacent bone. Cartilage was added at a constant physiological rate to simulate growth. Simulations showed that osteocyte signals from neighboring bone were sufficient for successful cartilage turnover, since equilibrium between cartilage remodeling and growth was obtained. Furthermore, there was good agreement between simulated bone structures and rat tibia histology, and the development of the trabecular architecture resembled that of infant long bones. Additionally, prohibiting osteoclast invasion resulted in thickened mineralized cartilage, similar to observations in a knock-out mouse model. We therefore conclude that it is well possible that osteocytes regulate the turnover of mineralized growth plate cartilage. PMID:21546025

  11. Osteosynthesis-screw augmentation by ultrasound-activated biopolymer - an ovine in vivo study assessing biocompatibility and bone-to-implant contact

    OpenAIRE

    Neumann, Hanjo; Breer, Stefan; Reimers, Nils; Kasch, Richard; Schulz, Arndt-Peter; Kienast, Benjamin

    2015-01-01

    Objectives Screw fixation and fragment anchoring in osteoporotic bones is often difficult. Problems like the cut out phenomenon and implant migration in osteoporotic bones have been reported. One possibility of improving the anchoring force of screws is augmentation of the screw. Cement-augmented screws in spinal surgery could exhibit a better anchoring in osteoporotic bones. Methods The purpose of this study was to examine the effect of screw augmentation using a resorbable polymer. Ultrasou...

  12. Rapidly resorbable vs. non-resorbable suture for experimental colonic anastomoses in rats--a randomized experimental study

    DEFF Research Database (Denmark)

    Klein, Mads; Pommergaard, Hans-Christian; Gögenur, Ismail; Rosenberg, Jacob

    2011-01-01

    Anastomotic dehiscence remains an important challenge for colorectal surgeons worldwide. Extensive research focused on performing a safe anastomosis is conducted with rats being the most used model when examining colorectal anastomoses. In daily clinical practice resorbable sutures are used when...

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2010-01-01

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

  15. Surgical Management of Oro-Antral Communications Using Resorbable GTR Membrane and FDMB Sandwich Technique: A Clinical Study.

    Science.gov (United States)

    Sandhya, G; Reddy, P Bal; Kumar, K A Jeevan; Sridhar Reddy, B; Prasad, N; Kiran, G

    2013-09-01

    The paper describes a new technique for closure of the oro-antral communication, in which both hard (bone) and soft tissue closure was achieved. The technique uses a Guided Tissue Regeeration (GTR) membrane and Freez Dried Mineralized Bone (FDMB) allograft for closure of the defect. Aim of the study was to assess the advantages of the surgical management of oro-antral communications using resorbable GTR membrane and FDMB sandwich technique. A total 10 patients were selected in whom dental extractions were complicated by formation of oro-antral communication (OAC). The resorbable guided tissue regeneration membrane (PERIOCOL-GTR) and freeze dried mineralized bone allograft material was used. Some cancellous granules of freeze dried bone allograft was sandwiched between sheaths of appropriately trimmed collagen membrane which was previously sutured together on three sides using 3/0 resorbable polyglycolic acid suture (vicryl). The fourth side was then adequately closed using the same suture after the bone graft had been inserted, thus creating a closed sandwich. The prepared sandwich was then tucked into the OAC in such a way that it formed a convexity towards the sinus and a concavity towards the alveolar bone. The rough surface of the sandwich is faced to the alveolar bone and additional bone graft is filled into this concavity. Suturing done without tension. Post-operative orthopantomogram was taken to radiologically quantify the amount of bone grafting/augmentation and closure of oro-antral fistula. There was an average of 11.84 mm bone formation after 6 months, the average width preserved and obtained was 6.9 mm. By the end of 4 months there was evidence of bone formation in 7 subjects and in three subjects bony trabeculae formed was almost similar to the adjacent bone. By the end of 6 months follow-up of 7 subjects showed trabeculae indistinguishable from the adjacent bone. The study was done in 10 patients with a follow-up period of 6 months and found to

  16. Molecular regulation of osteoclast activity.

    Science.gov (United States)

    Bruzzaniti, Angela; Baron, Roland

    2006-06-01

    Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed. PMID:16951988

  17. Alteration In Bones Metabolism In Active Rheumatoid Arthritis

    International Nuclear Information System (INIS)

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation and helps in corporating calcium into bone tissue. Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease characterized by bone complication including bone pain, erosion and osteoporosis. The aim of the present study is to evaluate some factors responsible in bone metabolism termed OC, vitamin D (vit. D), oncostatin M (OSM), ionized calcium and alkaline phosphatase. Fifty pre-menopausal female patients with active RA and twenty healthy controls of the same age were included in the present study. Radioimmunoassay (RIA) was used to estimate serum OC and active vitamin D. The quantitative determination of ionized calcium and alkaline phosphatase were carried out colorimetrically. OSM was measured by ELISA and serum levels of OC and active vitamin D were significantly decreased in RA patients as compared to those of the control group. On the other hand, the levels of serum OSM, ionized calcium and alkaline phosphatase were significantly increased in the RA patients as compared to their healthy control subjects. The results of this study indicated that early investigation and therapy of disturbances of bone metabolism in active RA are necessary for better prognosis and exhibited the importance of OC as a diagnostic tool of alterations of bone metabolism in RA patients.

  18. Influence of mineral phase in mineralization of a biocomposite containing chitosan, demineralized bone matrix and bone ash—in vitro study

    Indian Academy of Sciences (India)

    Krithiga Gunasekaran; Santhosh Kumar Baskar; Divya Sapphire Mohan; Thotapalli P Sastry

    2014-05-01

    A resorbable composite which acts as a active barrier in guided bone regeneration was fabricated using chitosan, demineralized bone matrix and bone ash. Its potential to form bone like apatite in simulated body fluid was assessed in this study. The mechanical strength of these composites was correlated with bone ash ratios and composites with better tensile strength were studied for their acellular bioactivity by incubating in simulated body fluid for 21 days. Composites without bone ash did not show acellular bioactivity which was confirmed by thermogravimetric analysis. In case of biocomposites with bone ash, there was an increase in residual weight indicating the mineralization of the composite. The composite containing bone ash has shown the peaks related to phosphate vibrations in its Fourier-transform infrared spectrum. Scanning micrographs revealed formation of apatite like crystals on its surface. Ca/P ratio was found to be 1.7 which is nearer to that of natural bone. Thus, prepared composites can be used as resorbable biocomposite in maxillofacial and oral defects.

  19. Crosstalk between cartilage and bone: when bone cytokines matter.

    Science.gov (United States)

    Funck-Brentano, Thomas; Cohen-Solal, Martine

    2011-04-01

    The cartilage damage which characterizes osteoarthritis is often accompanied by bone lesions. Joint integrity results from the balance in the physiological interactions between bone and cartilage. Several local factors regulate the physiological remodeling of cartilage, the disequilibrium of these leading to a higher cartilage catabolism. Several cytokines secreted by bone cells can induce chondrocyte differentiation, which suggests their role in the dialogue between both cells. Accumulative in vivo evidence shows that increased bone resorption occurs at an early stage in the development of osteoarthritis and that blocking bone-resorbing cytokines prevents cartilage damage, confirming the role of bone factors in the crosstalk of both tissues. Recently, molecules of the Wnt pathway have emerged as key regulators of bone and cartilage. Activation of Wnt/βcatenin induces an imbalance in cartilage homeostasis, and agonists/antagonists of Wnt are potential candidates for this interaction. This review will summarize what is known about the contribution of bone cytokines to the physiological remodeling of cartilage and in the pathophysiology of osteoarthritis. PMID:21596615

  20. [Bone marrow stromal damage mediated by immune response activity].

    Science.gov (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis. PMID:18173180

  1. Nanocrystalline biphasic resorbable calcium phosphate (HAp/β-TCP) thin film prepared by electron beam evaporation technique

    Energy Technology Data Exchange (ETDEWEB)

    Elayaraja, K.; Chandra, V. Sarath; Joshy, M.I. Ahymah; Suganthi, R.V. [Crystal Growth Centre, Anna University, Chennai 600025, Tamil Nadu (India); Asokan, K. [Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India); Kalkura, S. Narayana, E-mail: kalkura@yahoo.com [Crystal Growth Centre, Anna University, Chennai 600025, Tamil Nadu (India)

    2013-06-01

    Biphasic calcium phosphate (BCP) thin film having resorbable β-tricalcium phosphate (β-TCP) and non-resorbable hydroxyapatite (HAp) phases having enhanced bioactivity was synthesized by electron beam evaporation technique. Nanosized BCP was deposited as a layer (500 nm) on (0 0 1) silicon substrate by electron beam evaporation and crystalline phase of samples were found to improve on annealing at 700 °C. Uniform deposition of calcium phosphate on silicon substrate was verified from elemental mapping using scanning electron microscope (SEM-EDX). Annealing of the samples led to a decrease in surface roughness, hydrophobicity and dissolution of the coating layer. Amoxicillin loaded thin films exhibited significant bacterial resistance. In addition, BCP thin films did not exhibit any cytotoxicity. Antibiotics incorporated BCP coated implants might prevent the post-surgical infections and could promote bone-bonding of orthopedic devices.

  2. Nanocrystalline biphasic resorbable calcium phosphate (HAp/β-TCP) thin film prepared by electron beam evaporation technique

    International Nuclear Information System (INIS)

    Biphasic calcium phosphate (BCP) thin film having resorbable β-tricalcium phosphate (β-TCP) and non-resorbable hydroxyapatite (HAp) phases having enhanced bioactivity was synthesized by electron beam evaporation technique. Nanosized BCP was deposited as a layer (500 nm) on (0 0 1) silicon substrate by electron beam evaporation and crystalline phase of samples were found to improve on annealing at 700 °C. Uniform deposition of calcium phosphate on silicon substrate was verified from elemental mapping using scanning electron microscope (SEM-EDX). Annealing of the samples led to a decrease in surface roughness, hydrophobicity and dissolution of the coating layer. Amoxicillin loaded thin films exhibited significant bacterial resistance. In addition, BCP thin films did not exhibit any cytotoxicity. Antibiotics incorporated BCP coated implants might prevent the post-surgical infections and could promote bone-bonding of orthopedic devices.

  3. A novel combined surgical approach to vertical alveolar ridge augmentation with titanium mesh, resorbable membrane, and rhPDGF-BB: a retrospective consecutive case series.

    Science.gov (United States)

    Funato, Akiyoshi; Ishikawa, Tomohiro; Kitajima, Hajime; Yamada, Masahiro; Moroi, Hidetada

    2013-01-01

    The purpose of this case series was to report the clinical outcomes and histologic findings of vertical ridge augmentation using a combination of titanium mesh, resorbable collagen membrane, and recombinant human platelet-derived growth factor BB (rhPDGF-BB). Nineteen patients were included, and autogenous bone and anorganic bovine bone particles were used. The bone graft was mixed with rhPDGF-BB and loaded onto the bony defect up to the level of the adjacent alveolar crest. A pre-adapted titanium mesh was placed over the grafted region and covered with a resorbable collagen membrane, leaving no areas of the grafted region exposed. Seventeen patients exhibited good soft tissue healing. Postoperative flap dehiscence occurred relatively early in the healing period in one patient, whereas the covering collagen membrane was exposed during the later phase of the healing period in another. During reentry surgery for removal of the titanium mesh, three patients with favorable soft and hard tissue healing underwent bone biopsies for histologic evaluation of the augmented tissue just below the titanium mesh. The mean vertical height of augmented bone was 8.6 ± 4.0 mm. This report demonstrates the remarkable efficacy of guided bone regeneration using a combination of titanium mesh, resorbable collagen membrane, and rhPDGF for vertical ridge augmentation, thus expanding the indications for implant therapy and allowing recovery of the three-dimensional esthetic architecture in a severely absorbed alveolar ridge. PMID:23820701

  4. Instrumental neutron activation analysis of rib bone samples and of bone reference materials

    International Nuclear Information System (INIS)

    The instrumental neutron activation analysis method was used for the determination of trace elements in rib bone samples taken from autopsies of accident victims. The elements Br, Ca, Cl, Cr, Fe, Mg, Mn, Na, P, Sr, Rb and Zn were determined in cortical tissues by using short and long irradiations with thermal neutron flux of the IEA-R1m nuclear reactor. The reference materials NIST SRM 1400 Bone Ash and NIST SRM 1486 Bone Meal were also analyzed in order to evaluate the precision and the accuracy of the results. It was verified that lyophilization is the most convenient process for drying bone samples since it does not cause any element losses. Comparisons were made between the results obtained for rib samples and the literature values as well as between the results obtained for different ribs from a single individual and for bones from different individuals. (author)

  5. Abnormal bone remodelling in inflammatory arthritis

    Science.gov (United States)

    Bogoch, Earl R.; Moran, Erica

    1998-01-01

    Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis. PMID:9711159

  6. Bone microdamage and cell apoptosis

    OpenAIRE

    Noble B.

    2003-01-01

    Accumulation of microdamage in bone leads to the reduced strength of our skeleton. In health, bone adapts to the prevailing mechanical needs of the organism and is also capable of self-repair, sensing, removing and replacing damaged or mechanically insufficient volumes of bone. In disease and old age these characteristics are reduced. In order to undertake both of the processes of functional adaptation and repair the bone resorbing and forming cells must be very accurately targeted to areas o...

  7. Physical activity, bone density, and fragility fractures in women

    OpenAIRE

    Englund, Undis

    2009-01-01

    Scandinavia has among the highest incidence of fragility fractures in the world. The reasons for this are unknown, but might involve differences in genetic and/or environmental factors, such as sunlight exposure and levels of physical activity. Weight-bearing exercise is thought to have a beneficial effect on bone health in the young, but few studies have evaluated whether exercise in older subjects affects bone density and protects against fragility fractures. The initial objective of this t...

  8. Histologic analysis of resorbable blasting media surface implants retrieved from humans: a report of two cases.

    Science.gov (United States)

    Jeong, Kyung-In; Kim, Young-Kyun; Moon, Sang-Woon; Kim, Su-Gwan; Lim, Sung-Chul; Yun, Pil-Young

    2016-02-01

    The purpose of this study is to evaluate the degree of osseointegration of resorbable blasting media (RBM) surface implants retrieved from humans. Three implants in the mandibular molar region that were surface-treated with RBM were retrieved from two patients. The implants were used to manufacture specimens in order to measure the bone-implant contact (BIC) ratio. The BIC ratios of the three implants were found to be an average of 69.0%±9.1%. In conclusion, that RBM surface implants are integrated into the host environment with histological significance and the BIC ratio of the RBM surface-treated implant was not significantly different from that of other surface-treated implants. PMID:26904493

  9. Instrumental neutron activation analysis of prehistoric and ancient bone remains

    International Nuclear Information System (INIS)

    Instrumental neutron activation analysis (INAA) was used to study the element contents in bones of prehistoric dinosaurs and bones of an ancient bear and an archantrop (ancient person), which were found on the territory of Uzbekistan. Concentrations of more than 25 elements were in the range of 0.043-3600 mg/kg. Multielement analyses of bone and soil samples were carried out by INAA using the WWR-SM research nuclear reactor. Results of measurements have shown that in the dinosaurs bones the concentration of the rare earth elements (REEs) were within 280-3200 mg/kg; the uranium content reached a very high value, up to 180 mg/kg, while in soils coating the dinosaurs bones this content was 4.2 mg/kg; in the bones of the archantrop it was 1.53 mg/kg and in the bones of a standard person its amount is less than 0.016 mg/kg. (author)

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. The influence of bone surface availability in bone remodelling - A mathematical model including coupled geometrical and biomechanical regulations of bone cells

    OpenAIRE

    Pivonka, Peter; Buenzli, Pascal R.; Scheiner, Stefan; Hellmich, Christian; Dunstan, Colin R.

    2012-01-01

    Bone is a biomaterial undergoing continuous renewal. The renewal process is known as bone remodelling and is operated by bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Both biochemical and biomechanical regulatory mechanisms have been identified in the interaction between osteoclasts and osteoblasts. Here we focus on an additional and poorly understood potential regulatory mechanism of bone cells, that involves the morphology of the microstructure of bone. Bone cells...

  12. Biomechanical failure of metacarpal fracture resorbable plate fixation.

    Science.gov (United States)

    Lionelli, Gerald T; Korentager, Richard A

    2002-08-01

    Metacarpal fractures are a relatively common hand injury that may require operative intervention to ensure adequate reduction and stabilization. The use of permanent hardware, although acceptable, may lead to complications and an increased number of surgical procedures. The use of resorbable hardware such as poly-L-lactic acid and polyglycolic acid copolymer plates and screws may circumvent some of these complications. In vitro studies have demonstrated that the biomechanical characteristics of these resorbable plates may provide the rigid fixation necessary to allow for union of metacarpal fractures in vivo. However, limited clinical data are available regarding the success of their use in this application. The authors present what they believe is the first reported case of the failure of a poly-L-lactic acid and polyglycolic acid copolymer miniplate after use in the fixation of a metacarpal shaft fracture. PMID:12187350

  13. Application of Resorbable Poly(Lactide-co-Glycolide) with Entangled Hyaluronic Acid as an Autograft Extender for Posterolateral Intertransverse Lumbar Fusion in Rabbits

    OpenAIRE

    Walsh, William R.; Oliver, Rema A.; Gage, Gary; Yu, Yan; Bell, David; Bellemore, Jeremy; Adkisson, Huston Davis

    2010-01-01

    Facilitating fusion between bony segments in a reliable and reproducible manner using a synthetic bone graft material has a number of benefits for the surgeon as well as the patient. Although autograft remains the gold standard, associated comorbidities continue to drive the development of new biomaterials for use in spinal fusion. The ability of autograft alone and autograft combined with a radiolucent biomaterial composed of resorbable osteoconductive poly(lactide-co-glycolide) with entangl...

  14. Three Phase Bone Scintigraphy in Active and Inactive Osteomyelitis

    International Nuclear Information System (INIS)

    To Appreciate the value of bone scintigraphy in determination of the bony infection, we performed three phase bone scintigraphy in 34 cases of osteomyelitis of extremities prospectively. They were clinically inactive in 11 and active in 23 cases. We confirmed the active osteomyelitis by operation or aspiration within one week after scintigraphy. Perfusion, blood pool and delayed images were analyzed respectively and compared with the plain roentgenograms. All 23 active lesions showed diffusely increased perfusion in affected limbs. The areas of the increased activities on blood pool images were larger than or similar to those on delayed images in 17 cases (73.9%) with active osteomyelitis and smaller in 6 cases (26.1%). 5 of the latter 6 cases showed definite soft tissue activities on blood pool images. In inactive cases bone scintigrams were completely normal in 4 cases. Two of those were normal on plain films and remaining two showed mild focal bony sclerosis. Among 7 inactive lesions, perfusion was normal in 2 cases, diffusely increased in 4 cases and diffusely decreased in 1 case. 6 of these 7 cases showed increased activities both on blood pool and delayed images and the areas of increased activities on blood pool images didn't exceed those on delayed images. Bony sclerosis was noted on plain films in those 7 inactive lesions and the extent of the sclerosis correlated well to delayed images. Large blood pool activity was characteristics of active osteomyelitis. Normal three phase bone scintigram may indicate the time to terminate the treatment, but increased activity on perfusion and blood pool scans is not absolute indication of active lesion if the extent of the lesion on the blood pool image is smaller than that on delayed image and if no definite soft tissue activity is noted on perfusion and blood pool images in clinically inactive patient.

  15. A new biphasic osteoinductive calcium composite material with a negative Zeta potential for bone augmentation

    Directory of Open Access Journals (Sweden)

    Maciejewski Oliver

    2009-06-01

    Full Text Available Abstract The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential which was found to be favorable for bone regeneration and osseointegration of dental implants.

  16. Microcracks and Osteoclast Resorption Activity In Vitro

    OpenAIRE

    Rumpler, Monika; Würger, Tanja; Roschger, Paul; Zwettler, Elisabeth; Peterlik, Herwig; Fratzl, Peter; Klaushofer, Klaus

    2012-01-01

    During bone remodeling osteoclasts resorb bone, thus removing material, e.g., damaged by microcracks, which arises as a result of physiological loading and could reduce bone strength. Such a process needs targeted bone resorption exactly at damaged sites. Osteocytic signaling plays a key role in this process, but it is not excluded that osteoclasts per se may possess toposensitivity to recognize and resorb damaged bone since it has been shown that resorption spaces are associated with microcr...

  17. VEGF-C, a Lymphatic Growth Factor, Is a RANKL Target Gene in Osteoclasts That Enhances Osteoclastic Bone Resorption through an Autocrine Mechanism*S⃞

    OpenAIRE

    Qian ZHANG; Guo, Ruolin; Lu, Yan; Zhao, Lan; Zhou, Quan; Schwarz, Edward M.; Huang, Jing; Chen, Di; Jin, Zheng-Gen; Boyce, Brendan F.; Xing, Lianping

    2008-01-01

    Osteoclasts are bone-resorbing cells, but they also secrete and respond to cytokines. Here, we test the hypothesis that osteoclasts secrete the lymphatic growth factor, VEGF-C, to increase their resorptive activity. Osteoclasts and osteoclast precursors were generated by culturing splenocytes with macrophage colony-stimulating factor and RANKL from wild-type, NF-κBp50-/-/p52-/-, and Src-/- mice. Expression of VEGFs was measured by real time reverse transcription-PC...

  18. RANK, RANKL and osteoprotegerin in arthritic bone loss

    Directory of Open Access Journals (Sweden)

    M.C. Bezerra

    2005-02-01

    Full Text Available Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1, IL-6, IL-11, IL-17, tumor necrosis factor-alpha, prostaglandin E2, or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-ß released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.

  19. Antimicrobial activity of bone cements embedded with organic nanoparticles

    Directory of Open Access Journals (Sweden)

    Perni S

    2015-10-01

    Full Text Available Stefano Perni,1,2 Victorien Thenault,1 Pauline Abdo,1 Katrin Margulis,3 Shlomo Magdassi,3 Polina Prokopovich1,2 1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; 2Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; 3Casali Institute, Institute of Chemistry, The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem, IsraelAbstract: Infections after orthopedic surgery are a very unwelcome outcome; despite the widespread use of antibiotics, their incidence can be as high as 10%. This risk is likely to increase as antibiotics are gradually losing efficacy as a result of bacterial resistance; therefore, novel antimicrobial approaches are required. Parabens are a class of compounds whose antimicrobial activity is employed in many cosmetic and pharmaceutical products. We developed propylparaben nanoparticles that are hydrophilic, thus expanding the applicability of parabens to aqueous systems. In this paper we assess the possibility of employing paraben nanoparticles as antimicrobial compound in bone cements. The nanoparticles were embedded in various types of bone cement (poly(methyl methacrylate [PMMA], hydroxyapatite, and brushite and the antimicrobial activity was determined against common causes of postorthopedic surgery infections such as: Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, and Acinetobacter baumannii. Nanoparticles at concentrations as low as 1% w/w in brushite bone cement were capable of preventing pathogens growth, 5% w/w was needed for hydroxyapatite bone cement, while 7% w/w was required for PMMA bone cement. No ­detrimental effect was determined by the addition of paraben nanoparticles on bone cement compression strength and cytocompatibility. Our results demonstrate that paraben nanoparticles can be encapsulated in bone cement, providing concentration-dependent antimicrobial

  20. Data Mining Activities for Bone Discipline - Current Status

    Science.gov (United States)

    Sibonga, J. D.; Pietrzyk, R. A.; Johnston, S. L.; Arnaud, S. B.

    2008-01-01

    The disciplinary goals of the Human Research Program are broadly discussed. There is a critical need to identify gaps in the evidence that would substantiate a skeletal health risk during and after spaceflight missions. As a result, data mining activities will be engaged to gather reviews of medical data and flight analog data and to propose additional measures and specific analyses. Several studies are briefly reviewed which have topics that partially address these gaps in knowledge, including bone strength recovery with recovery of bone mass density, current renal stone formation knowledge, herniated discs, and a review of bed rest studies conducted at Ames Human Research Facility.

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

    Science.gov (United States)

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

    2014-01-10

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

  2. Mechanical and Histological Effects of Resorbable Blasting Media Surface Treatment on the Initial Stability of Orthodontic Mini-Implants.

    Science.gov (United States)

    Gansukh, Odontuya; Jeong, Jong-Wha; Kim, Jong-Wan; Lee, Jong-Ho; Kim, Tae-Woo

    2016-01-01

    Introduction. This study aimed to evaluate the effects of resorbable blasting media (RBM) treatment on early stability of orthodontic mini-implants by mechanical, histomorphometric, and histological analyses. Methods. Ninety-six (64 for mechanical study and 32 for histological study and histomorphometric analysis) titanium orthodontic mini-implants (OMIs) with machined (machined group) or RBM-treated (CaP) surface (RBM group) were implanted in the tibiae of 24 rabbits. Maximum initial torque (MIT) was measured during insertion, and maximum removal torque (MRT) and removal angular momentum (RAM) were measured at 2 and 4 weeks after implantation. Bone-to-implant contact (BIC) and bone area (BA) were analyzed at 4 weeks after implantation. Results. RBM group exhibited significantly lower MIT and significantly higher MRT and RAM at 2 weeks than machined group. No significant difference in MRT, RAM, and BIC between the two groups was noted at 4 weeks, although BA was significantly higher in RBM group than in machined group. RBM group showed little bone resorption, whereas machined group showed new bone formation after bone resorption. Conclusions. RBM surface treatment can provide early stability of OMIs around 2 weeks after insertion, whereas stability of machined surface OMIs may decrease in early stages because of bone resorption, although it can subsequently recover by new bone apposition. PMID:26942200

  3. Effect of acceleration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    Science.gov (United States)

    Suzuki, S.; Kitamura, K.; Nemoto, N.; Shimizu, S.; Wada, W.; Kondo, K.; Tabata, T.; Sodeyama, S.; Ijiri, I.; Hattori, H.

    It is well known that hypo-gravity and hyper-gravity influence bone metabolism However basic data concerning the mechanism are a few because no in vitro model system of human bone is available Human bone consists of osteoblasts osteoclasts and the bone matrix No technique for the co-culture of these components has ever been developed Fish scale is a calcified tissue that contains osteoblasts osteoclasts and bone matrix all of which are similar to those found in human bone Recently we developed a new in vitro model system using goldfish scale This system can simultaneously detect the activities of both scale osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers Using this system we analyzed the bone metabolism under acceleration with a custom-made G-load apparatus Osteoclastic activity in the goldfish scales was suppressed under low-acceleration 0 5-G while osteoblastic activity did not change under this acceleration Under high-acceleration 6-G however the osteoblastic activity of the scales increased In addition the osteoclastic activity of the scales decreased These results suggest that both osteoblastic and osteoclastic activities are regulated by the strength of acceleration Therefore we strongly believe that our in vitro system is useful for analysis of bone metabolism under acceleration

  4. Medium-Term Function of a 3D Printed TCP/HA Structure as a New Osteoconductive Scaffold for Vertical Bone Augmentation: A Simulation by BMP-2 Activation

    Directory of Open Access Journals (Sweden)

    Mira Moussa

    2015-04-01

    Full Text Available Introduction: A 3D-printed construct made of orthogonally layered strands of tricalcium phosphate (TCP and hydroxyapatite has recently become available. The material provides excellent osteoconductivity. We simulated a medium-term experiment in a sheep calvarial model by priming the blocks with BMP-2. Vertical bone growth/maturation and material resorption were evaluated. Materials and methods: Titanium hemispherical caps were filled with either bare- or BMP-2 primed constructs and placed onto the calvaria of adult sheep (n = 8. Histomorphometry was performed after 8 and 16 weeks. Results: After 8 weeks, relative to bare constructs, BMP-2 stimulation led to a two-fold increase in bone volume (Bare: 22% ± 2.1%; BMP-2 primed: 50% ± 3% and a 3-fold decrease in substitute volume (Bare: 47% ± 5%; BMP-2 primed: 18% ± 2%. These rates were still observed at 16 weeks. The new bone grew and matured to a haversian-like structure while the substitute material resorbed via cell- and chemical-mediation. Conclusion: By priming the 3D construct with BMP-2, bone metabolism was physiologically accelerated, that is, enhancing vertical bone growth and maturation as well as material bioresorption. The scaffolding function of the block was maintained, leaving time for the bone to grow and mature to a haversian-like structure. In parallel, the material resorbed via cell-mediated and chemical processes. These promising results must be confirmed in clinical tests.

  5. A Resorbable Calcium-Deficient Hydroxyapatite Hydrogel Composite for Osseous Regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Hutchens, Stacy A [ORNL; O' Neill, Hugh Michael [ORNL; Benson, Roberto S. [University of Tennessee, Knoxville (UTK); Evans, Barbara R [ORNL; Rawn, Claudia J [ORNL

    2009-01-01

    It was previously discovered that the unique structure and chemistry of bacterial cellulose (BC) permits the formation of calcium-deficient hydroxyapatite (CdHAP) nanocrystallites under aqueous conditions at ambient pH and temperature. In this study, BC was chemically modified via a limited periodate oxidation reaction to render the composite degradable and thus more suitable for bone regeneration. While native BC does not degrade in mammalian systems, periodate oxidation yields dialdehyde cellulose which breaks down at physiological pH. The composite was characterized by tensile testing, X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. X-ray diffraction showed that oxidized BC retains its structure and could biomimetically form CdHAP. Degradation behavior was analyzed by incubating the samples in simulated physiological fluid (pH 7.4) at 37 C under static and dynamic conditions. The oxidized BC and oxidized BC-CdHAP composites both lost significant mass after exposure to the simulated physiological environment. Examination of the incubation solutions by UV-Vis spectrophotometric analysis demonstrated that, while native BC released only small amounts of soluble cellulose fragments, oxidized cellulose releases carbonyl containing degradation products as well as soluble cellulose fragments. By entrapping CdHAP in a degradable hydrogel carrier, this composite should elicit bone regeneration then resorb over time to be replaced by new osseous tissue.

  6. Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling

    Science.gov (United States)

    Menéndez-Gutiérrez, María P.; Rőszer, Tamás; Fuentes, Lucía; Núñez, Vanessa; Escolano, Amelia; Redondo, Juan Miguel; De Clerck, Nora; Metzger, Daniel; Valledor, Annabel F.; Ricote, Mercedes

    2015-01-01

    Osteoclasts are bone-resorbing cells that are important for maintenance of bone remodeling and mineral homeostasis. Regulation of osteoclast differentiation and activity is important for the pathogenesis and treatment of diseases associated with bone loss. Here, we demonstrate that retinoid X receptors (RXRs) are key elements of the transcriptional program of differentiating osteoclasts. Loss of RXR function in hematopoietic cells resulted in formation of giant, nonresorbing osteoclasts and increased bone mass in male mice and protected female mice from bone loss following ovariectomy, which induces osteoporosis in WT females. The increase in bone mass associated with RXR deficiency was due to lack of expression of the RXR-dependent transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MAFB) in osteoclast progenitors. Evaluation of osteoclast progenitor cells revealed that RXR homodimers directly target and bind to the Mafb promoter, and this interaction is required for proper osteoclast proliferation, differentiation, and activity. Pharmacological activation of RXRs inhibited osteoclast differentiation due to the formation of RXR/liver X receptor (LXR) heterodimers, which induced expression of sterol regulatory element binding protein-1c (SREBP-1c), resulting in indirect MAFB upregulation. Our study reveals that RXR signaling mediates bone homeostasis and suggests that RXRs have potential as targets for the treatment of bone pathologies such as osteoporosis. PMID:25574839

  7. Bone

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-01-01

    Dental and periodontal tissue development is a complex process involving various cell-types. A finely orchestrated network of communications between these cells is implicated. During early development, communications between cells from the oral epithelium and the underlying mesenchyme govern the dental morphogenesis with successive bud, cap and bell stages. Later, interactions between epithelial and mesenchymal cells occur during dental root elongation. Root elongation and tooth eruption require resorption of surrounding alveolar bone to occur. For years, it was postulated that signaling molecules secreted by dental and periodontal cells control bone resorbing osteoclast precursor recruitment and differentiation. Reverse signaling originating from bone cells (osteoclasts and osteoblasts) toward dental cells was not suspected. Dental defects reported in osteopetrosis were associated with mechanical stress secondary to defective bone resorption. In the last decade, consequences of bone resorption over-activation on dental and periodontal tissue formation have been analyzed with transgenic animals (RANKTg and Opg−∕− mice). Results suggest the existence of signals originating from osteoclasts toward dental and periodontal cells. Meanwhile, experiments consisting in transitory inhibition of bone resorption during root elongation, achieved with bone resorption inhibitors having different mechanisms of action (bisphosphonates and RANKL blocking antibodies), have evidenced dental and periodontal defects that support the presence of signals originating bone cells toward dental cells. The aim of the present manuscript is to present the data we have collected in the last years that support the hypothesis of a role of bone resorption in dental and periodontal development. PMID:26594180

  9. Influence of bone marrow fat embolism on coagulation activation in an ovine model of vertebroplasty

    OpenAIRE

    Krebs, J; Ferguson, S. J.; Hoerstrup, S P; Goss, B G; Haeberli, A; Aebli, N

    2008-01-01

    BACKGROUND: Intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially serious complication during vertebroplasty. The release of fatty material and thromboplastin from the bone marrow cavity during vertebroplasty may activate the coagulation cascade resulting in thrombogenesis, and pharmacological prophylaxis may therefore prevent cardiovascular complications. Thus, the effects of bone marrow fat embolism on coagulation activation du...

  10. Top 10 Research Questions Related to Physical Activity and Bone Health in Children and Adolescents

    Science.gov (United States)

    Janz, Kathleen F.; Thomas, David Q.; Ford, M. Allison; Williams, Skip M.

    2015-01-01

    Evidence strongly supports a positive, causal effect of physical activity on bone strength and suggests long-term benefits of childhood physical activity to the prevention of osteoporosis. The contribution of healthy bone development in youth is likely to be as important to fracture prevention as the amount of late adulthood bone loss. Families,…

  11. The intensity of physical activity influences bone mineral accrual in childhood

    DEFF Research Database (Denmark)

    Heidemann, Malene Søborg; Mølgaard, Christian; Husby, Steffen;

    2013-01-01

    Background Studies indicate genetic and lifestyle factors can contribute to optimal bone development. In particular, the intensity level of physical activity may have an impact on bone health. This study aims to assess the relationship between physical activity at different intensities and Bone M...

  12. The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts.

    Science.gov (United States)

    Huang, Su; Eleniste, Pierre P; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A; Mains, Richard E; Allen, Matthew R; Bruzzaniti, Angela

    2014-03-01

    Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and found that it was expressed in osteoclasts and osteoblasts. Furthermore, micro-CT analyses of the distal femur of global Kalirin knockout (Kal-KO) mice revealed significantly reduced trabecular and cortical bone parameters in Kal-KO mice, compared to WT mice, with significantly reduced bone mass in 8, 14 and 36week-old female Kal-KO mice. Male mice also exhibited a decrease in bone parameters but not to the level seen in female mice. Histomorphometric analyses also revealed decreased bone formation rate in 14week-old female Kal-KO mice, as well as decreased osteoblast number/bone surface and increased osteoclast surface/bone surface. Consistent with our in vivo findings, the bone resorbing activity and differentiation of Kal-KO osteoclasts was increased in vitro. Although alkaline phosphatase activity by Kal-KO osteoblasts was increased in vitro, Kal-KO osteoblasts showed decreased mineralizing activity, as well as decreased secretion of OPG, which was inversely correlated with ERK activity. Taken together, our findings suggest that deletion of Kalirin directly affects osteoclast and osteoblast activity, leading to decreased OPG secretion by osteoblasts which is likely to alter the RANKL/OPG ratio and promote osteoclastogenesis. Therefore, Kalirin may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass. PMID:24380811

  13. New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation.

    Science.gov (United States)

    Wan, You

    2016-01-01

    In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation. PMID:26900062

  14. Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings.

    Science.gov (United States)

    Kim, Jinku; Magno, Maria Hanshella R; Ortiz, Ophir; McBride, Sean; Darr, Aniq; Kohn, Joachim; Hollinger, Jeffrey O

    2015-03-01

    Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components. In this article, we continue our exploration of E1001(1k), a tyrosine-derived polycarbonate, as an orthopedic implant material. Specifically, we use E1001(1k), which is degradable, nontoxic, and osteoconductive, to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate (CP) coatings: in one case, pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure (E1001(1k) + CP). In the other case, bone matrix minerals (BMM) such as zinc, manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating (E1001(1k) + BMM). These scaffold compositions were compared against each other and against ChronOS (Synthes USA, West Chester, PA, USA), a clinically used bone graft substitute (BGS), which served as the positive control in our experimental design. This BGS is composed of poly(lactide co-ε-caprolactone) and beta-tricalcium phosphate. We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions. New bone formation was determined after 2, 4, 6, 8 and 12 weeks by micro-computerized tomography (μCT) and histology. The experimental tyrosine-derived polycarbonate, enhanced with dicalcium phosphate dihydrate, E1001(1k) + CP, supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM, E1001(1k) + BMM. The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k) scaffolds. At all time points, there was a trend for E1001(1k) + CP to be superior to the commercial BGS. However, only at the 6-week time point did this trend reach statistical significance

  15. Comparison of morphological changes in efferent lymph nodes after implantation of resorbable and non-resorbable implants in rabbits

    Directory of Open Access Journals (Sweden)

    Angrisani Nina

    2011-04-01

    Full Text Available Abstract Background Magnesium alloys as biodegradable implant materials received much interest in recent years. It is known that products of implant degradation can induce several types of immune response. Hence, the aim of this study was to examine the morphological changes of efferent lymph nodes after implantation of different resorbable magnesium alloys (MgCa0.8, LAE442 in comparison to commercially available resorbable (PLA and non-resorbable (titanium implant materials as well as control groups without implant material. Methods The different implant materials were inserted intramedullary into the rabbit tibia. After postoperative observation periods of three and six months, popliteal lymph nodes were examined histologically and immunhistologically and compared to lymph nodes of sham operated animals and animals without surgery. Haematoxylin and eosin staining was performed for cell differentiation. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection, mouse anti-CD68 primary antibodies for macrophage detection. Evaluation of all sections was performed applying a semi quantitative score. Results The histological evaluation demonstrated low and moderate levels of morphological changes for both magnesium alloys (LAE442 and MgCa0.8. Higher than moderate values were reached for titanium in sinus histiocytosis and histiocytic apoptosis (3 months and for PLA in histiocytic apoptosis (3 and 6 months. The immune response to all investigated implants had a non-specific character and predominantly was a foreign-body reaction. LAE442 provoked the lowest changes which might be due to a lower degradation rate in comparison to MgCa0.8. Therewith it is a promising candidate for implants with low immunogenic potential. Conclusion Both examined magnesium alloys did not cause significantly increased morphological changes in efferent lymph nodes in comparison to the widely used implant materials titanium

  16. Multielement analysis of iliac crest bone by neutron activation

    International Nuclear Information System (INIS)

    Bone samples from iliac crest were obtained from apparently healthy female (n = 4) and male (n = 8) subjects with ages between 15-50. Cortical and trabecular parts were separated and soft tissues like fat, muscle and blood were removed. Calcium, Mg, Na, Cl, Fe, Zn, Br, Sr, and Cs were determined by instrumental neutron activation analysis and other techniques, and their relations were discussed. Fairly good agreement was obtained with literature data. These values may serve as reference values for subjects from a Turkish population. (author)

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

    OpenAIRE

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

    2012-01-01

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

  18. Surface characterization and in vivo evaluation of laser sintered and machined implants followed by resorbable-blasting media process: A study in sheep

    Science.gov (United States)

    Bowers, Michelle; Yoo, Daniel; Marin, Charles; Gil, Luiz; Shabaka, Nour; Goldstein, Matt; Janal, Malvin; Tovar, Nick; Bonfante, Estevam; Coelho, Paulo

    2016-01-01

    Background This study aimed to compare the histomorphometric and histological bone response to laser-sintered implants followed by resorbable-blasting media (RBM) process relative to standard machined/RBM surface treated implants. Material and Methods Six male sheep (n=6) received 2 Ti-6Al-4V implants (1 per surface) in each side of the mandible for 6 weeks in vivo. The histomorphometric parameters bone-implant contact (BIC) and bone area fraction occupancy (BAFO) were evaluated. Results Optical interferometry revealed higher Sa and Sq values for the laser-sintered/RBM surface in relation to standard/RBM implants. No significant differences in BIC were observed between the two groups (p>0.2), but significantly higher BAFO was observed for standard/RBM implants (p<0.01). Conclusions The present study demonstrated that both surfaces were biocompatible and osseoconductive, and the combination of laser sintering and RBM has no advantage over the standard machined implants with subsequent RBM. Key words:Dental implants, osseointegration, resorbable- blasting media, sheep, in vivo. PMID:26827064

  19. Fixation of a severely resorbed mandible for complete arch screw-retained rehabilitation: A clinical report.

    Science.gov (United States)

    Fabris, Vinicius; Bacchi, Atais

    2016-05-01

    Severely resorbed mandibles with placed endosteal dental implants can fracture. Therefore, techniques to reduce the risk or minimize the consequences of these fractures are needed. This clinical report presents a technique for placing a titanium plate in a severely resorbed mandible subjected to complete-arch implant therapy. The titanium plate is placed in the same surgical procedure as the implants, allowing immediate implant loading. This technique provides safe implant-supported treatment for patients with severe mandibular resorption. PMID:26775245

  20. Internal fixation for coronal shear fracture of the capitellum with polylactide resorbable fixation

    OpenAIRE

    Kraan, Gerald A; Krijnen, Matthijs R; Eerenberg, Jan Peter

    2013-01-01

    A 24-year-old woman with pain in the right elbow after a fall demonstrated a coronal shear fracture on radiographic studies. Perioperative a coronal shear fracture was seen and treated successfully with a polylactide Rigid fix resorbable pin. The operative correction resulted in normal function at 6 months follow-up. We state that a capitellum shear fracture can be fixated with a single resorbable pin, leading to successful fusion.

  1. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

  2. Effect of vibration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    Science.gov (United States)

    Suzuki, N.; Kitamura, K.; Nemoto, T.; Shimizu, N.; Wada, S.; Kondo, T.; Tabata, M. J.; Sodeyama, F.; Ijiri, K.; Hattori, A.

    In osteoclastic activity during space flight as well as hind limb unloading by tail suspension, inconsistent results have been reported in an in vivo study. The bone matrix plays an important role in the response to physical stress. However, there is no suitable in vitro co-culture system of osteoblasts and osteoclasts including bone matrix. On the other hand, fish scale is a calcified tissue that contains osteoblasts, osteoclasts, and bone matrix, all of which are similar to those found in human bones. Recently, we developed a new in vitro model system using goldfish scale. This system can detect the activities of osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers and precisely analyze the co-relationship between osteoblasts and osteoclasts. Using this system, we analyzed the bone metabolism under various degrees of acceleration (0.5-, 1-, 2-, 4-, and 6-G) by vibration with a G-load apparatus. After loading for 5 and 10 min, the scales were incubated for 6 and 24 h. The osteoblastic and osteoclastic activities were then measured. The osteoblastic activities gradually increased corresponding to 1-G to 6-G acceleration. In addition, ER mRNA expression was the highest under 6-G acceleration. On the other hand, the osteoclastic activity decreased at 24 h of incubation under low acceleration (0.5- and 1-G). This change coincided with TRAP mRNA expression. Under 2-G acceleration, the strength of suppression in osteoclastic activity was the highest. The strength of the inhibitory action under 4- and 6-G acceleration was lower than that under 2-G acceleration. In our co-culture system, osteoblasts and osteoclasts in the scale sensitively responded to several degrees of acceleration. Therefore, we strongly believe that our in vitro co-culture system is useful for the analysis of bone metabolism under loading or unloading.

  3. Bone-inducing Activity of Biological Piezoelectric Ceramic

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To simulate the piezoelectric effect of nature bone, two kinds of biological piezoelectric composite ceramics consisted of hydroxyapatite ( HA ) and lithium sodium potassium riobate (LNK) ceramic of which the ratio of HA/ LNK was 1: 10 and 5:5( wt/ wt ) were prepared. Their piezoelectric property and growth of apatite crystal in the ceramics surface were investigated. With the increase of LNK amount, piezoelectric activity increased correspondingly. By immersing the poled piezoelectric ceramics in simulated body fluid (SBF) at 36.5 ℃ for 7,14, and 21 days, apatite crystal was formed on negatively charged surfaces. After 21 days immersion in SBF,the thickest apatite crystal on the negatively charged surfaces increased to 3.337μm. The novel biological piezoelectric ceramics show an excellent piezoelectric property and superior potential bioactivity.

  4. Postirradiation proliferative activity and morphology of human bone marrow

    International Nuclear Information System (INIS)

    Bone marrow cells distribution by cell cycle stages (S, G1/0, G2+M) were studied by flow cytometry and myelograms analyzed in 13 subjects occupationally irradiated during an emergency situation, in 19 patients administered radiotherapy, and in 26 normal subjects. Low-dose (0,2 to 0,4 Gy) exposure was associated with an increase of proliferative activity, higher doses (1 to 4 Gy) caused a reduction of the share of cells in the phase of DNA synthesis and an expressed block at the C2+M stage. The studied parameters of cellular cycle reflect the degree of radiation exposure and together with myelogram values may be regarded as diagnostic characteristics of hemopoiesis. 10 refs., 4 figs., 1 tab

  5. Activation of Bone Remodeling after Fatigue: Differential Response to Linear Microcracks and Diffuse Damage

    OpenAIRE

    Herman, B.C.; Cardoso, L; Majeska, R.J.; Jepsen, K.J.; Schaffler, M.B.

    2010-01-01

    Recent experiments point to two predominant forms of fatigue microdamage in bone: linear microcracks (tens to a few hundreds microns in length) and “diffuse damage” (patches of diffuse stain uptake in fatigued bone comprised of clusters of sublamellar-sized cracks). The physiological relevance of diffuse damage in activating bone remodeling is not known. In this study microdamage amount and type were varied to assess whether linear or diffuse microdamage have similar effects on the activation...

  6. Interleukin-2 stimulates osteoclastic activity: Increased acid production and radioactive calcium release

    International Nuclear Information System (INIS)

    Recombinant human interleukin-2 (IL-2) was studied to determine effects on acid production by individual osteoclasts in situ on mouse calvarial bones. This analysis was performed using a microspectrofluorimetric technique to quantify acid production in individual cells. Radioactive calcium release was determined using calvarial bones in a standard tissue culture system. This allowed us to correlate changes in acid production with a measure of bone resorption. IL-2 stimulated acid production and bone resorbing activity. Both effects were inhibited by calcitonin. No stimulation of bone resorption occurred when IL-2-containing test media was incubated with a specific anti-IL-2 antibody and ultrafiltered. Our data demonstrated a correlation between acid production and bone resorbing activity in mouse calvaria exposed to parathyroid hormone (PTH). The data obtained from cultured mouse calvaria exposed to IL-2 demonstrated similar stimulatory effects to those seen during PTH exposure. These data suggest that calvaria exposed to IL-2 in vitro have increased osteoclastic acid production corresponding with increased bone resorption. (author)

  7. Bone Remodeling and Hydroxyapatite Resorption in Coated Primary Hip Prostheses

    OpenAIRE

    Tonino, Alphons J.; van der Wal, Bart C. H.; Heyligers, Ide C.; Grimm, Bernd

    2008-01-01

    Hydroxyapatite coatings for THA promote bone ongrowth, but bone and coating are exposed to stress shielding-driven osteoclastic resorption. We asked: (1) if the resorption of hydroxyapatite coating and bone ongrowth correlated with demographics; (2) if the resorption related to the stem level; and (3) what happens to the implant-bone interface when all hydroxyapatite coating is resorbed? We recovered 13 femoral components from cadaveric specimens 3.3 to 11.2 years after uneventful primary THA...

  8. Effects of a perfusion bioreactor activated novel bone substitute in spine fusion in sheep

    DEFF Research Database (Denmark)

    Sørensen, Jesper Roed; Koroma, Kariatta Ester; Ding, Ming; Wendt, David; Jespersen, Stig; Juhl, Maria Vinther; Theilgaard, Naseem; Martin, Ivan; Overgaard, Søren

    2012-01-01

    To evaluate the effect of a large perfusion-bioreactor cell-activated bone substitute, on a two-level large posterolateral spine fusion sheep model.......To evaluate the effect of a large perfusion-bioreactor cell-activated bone substitute, on a two-level large posterolateral spine fusion sheep model....

  9. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.

    2014-03-01

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  10. Investigation of environmental activity levels of bone-coal mining area in five provinces

    International Nuclear Information System (INIS)

    During 1991-1993, the activity levels of the bone-coal mines were investigated in Zhejiang, Hubei, Hunan, Jiangxi and Anhui Province, respectively, where the reserve of bone-coal is about 90% of our country's total reserve. The average of γ radiation dose rate level measured for bone-coal, bone-coal cinder (BCC) and bone-coal cinder brick (BCCB) in these provinces is about 500 nGy/h, 400 nGy/h and 700 nGy/h respectively, while that for fields, roads and houses made of BCCB in corresponding regions of these provinces is about 200 nGy/h, 260 nGy/h and 300 nGy/h respectively. It is shown that the environmental activity level of bone-coal mining area is about 3 times higher than the reference spots. (authors)

  11. Human breast cancer cell-mediated bone collagen degradation requires plasminogen activation and matrix metalloproteinase activity

    Directory of Open Access Journals (Sweden)

    Hill Peter A

    2005-02-01

    Full Text Available Abstract Background Breast cancer cells frequently metastasize to the skeleton and induce extensive bone destruction. Cancer cells produce proteinases, including matrix metalloproteinases (MMPs and the plasminogen activator system (PAS which promote invasion of extracellular matrices, but whether these proteinases degrade bone matrix is unclear. To characterize the role that breast cancer cell proteinases play in bone degradation we compared the effects of three human breast cancer cell lines, MDA-MB-231, ZR-75-1 and MCF-7 with those of a normal breast epithelial cell line, HME. The cell lines were cultured atop radiolabelled matrices of either mineralized or non-mineralized bone or type I collagen, the principal organic constituent of bone. Results The 3 breast cancer cell lines all produced significant degradation of the 3 collagenous extracellular matrices (ECMs whilst the normal breast cell line was without effect. Breast cancer cells displayed an absolute requirement for serum to dissolve collagen. Degradation of collagen was abolished in plasminogen-depleted serum and could be restored by the addition of exogenous plasminogen. Localization of plasmin activity to the cell surface was critical for the degradation process as aprotinin, but not α2 antiplasmin, prevented collagen dissolution. During ECM degradation breast cancer cell lines expressed urokinase-type plasminogen activator (u-PA and uPA receptor, and MMPs-1, -3, -9,-13, and -14. The normal breast epithelial cell line expressed low levels of MMPs-1, and -3, uPA and uPA receptor. Inhibitors of both the PAS (aprotinin and PA inhibitor-1 and MMPs (CT1166 and tisue inhibitor of metalloproteinase blocked collagen degradation, demonstrating the requirement of both plasminogen activation and MMP activity for degradation. The activation of MMP-13 in human breast cancer cells was prevented by plasminogen activator inhibitor-1 but not by tissue inhibitor of metalloproteinase-1, suggesting

  12. Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

    International Nuclear Information System (INIS)

    The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

  13. Nonspecific collagenolytic activity of the femoral bone in immobilized rat extremities.

    Science.gov (United States)

    Prokopová, D; Tesárek, B; Susta, A

    1975-01-01

    Nonspecific collagenolytic activity was studied in rat bones after immobilization. The left hind limb was immobilized by sectioning the sciatic nerve. Enzyme activity was determined by using synthetic pentapeptide substrate (Pz-Pro-Leu-Gly-Pro-D-Arg). After immobilization the activity of nonspecific collagenase increased and reached its maximum on the third day after the operation. The activity was decreased after one week and attained levels of control bones three weeks after sciatic nerve section. PMID:167392

  14. Bone metabolic activity in hyperostosis cranialis interna measured with {sup 18}F-fluoride PET

    Energy Technology Data Exchange (ETDEWEB)

    Waterval, Jerome J.; Dongen, Thijs M.A. van; Stokroos, Robert J.; Manni, Johannes J. [Maastricht University Medical Center, Department of Otorhinolaryngology and Head and Neck Surgery, Maastricht (Netherlands); Teule, Jaap G.J.; Kemerink, Gerrit J.; Brans, Boudewijn [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Nieman, Fred H.M. [Maastricht University Medical Center, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht (Netherlands)

    2011-05-15

    {sup 18}F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent {sup 18}F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average {sup 18}F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. {sup 18}F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. {sup 18}F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that {sup 18}F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course. (orig.)

  15. Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET

    International Nuclear Information System (INIS)

    18F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent 18F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average 18F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. 18F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. 18F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that 18F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course. (orig.)

  16. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, N; Glerup, H; Rungby, Jørgen;

    2000-01-01

    histomorphometric findings. MARKERS OF BONE FORMATION: Serum C-terminal propeptide of procollagen I (PICP) and serum bone-specific alkaline phosphatase (bAP) showed significant correlations with the dynamic parameters of bone formation (r=0.57-0.58), whereas serum osteocalcin and serum total AP did not. CYTOKINES......: Highly significant correlations were observed between marrow IL-6 and rates of bone resorption and activation frequency (r=0.76-0.82) and with serum ICTP (r=0.63). Minor, but also significant correlations were observed between the resorptive indices and IL-6sR and IL-1beta. The data indicate that...

  17. Diabetes mellitus related bone metabolism and periodontal disease

    Institute of Scientific and Technical Information of China (English)

    Ying-Ying Wu; E Xiao; Dana T Graves

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  18. Bone marrow fibrosis with fibrocytic and immunoregulatory responses induced by β-catenin activation in osteoprogenitors.

    Science.gov (United States)

    Yu, Jian; Cao, Jingjing; Li, Hanjun; Liu, Pei; Xu, Shuqin; Zhou, Rujiang; Yao, Zhengju; Guo, Xizhi

    2016-03-01

    Wnt/β-catenin signaling has been reported to contribute to the development of bone fibrous dysplasia. However, it remains unclear whether fibrocytes and immune cells are involved in this β-catenin-mediated bone marrow fibrosis. In this study, we showed that constitutive activation of β-catenin by Col1a1-Cre (3.6-kb) exhibited bone marrow fibrosis, featured with expanded populations of fibrocytes, myofibroblasts and osteoprogenitors. Lineage tracing and IHC examinations showed that Col3.6-Cre display Cre recombinase activity not only in osteoprogenitors, but also in monocyte-derived fibrocytes in the endosteal niches of bones. Additionally, β-catenin stimulated the secretion of cytokines and pro-fibrotic signals in bone marrow, including GM-CSF, TGFβ1 and VEGF. Consequently, the frequency of differentiated immature monocyte-derived dendritic cells and naïve T cells was markedly increased in the mutant bone marrow. These phenotypes were quite different from those following β-catenin activation in mature osteoblasts driven by Col1a1-Cre (2.3-kb). Our findings suggested that a conserved pro-fibrotic signal cascade might underlie β-catenin-mediated bone marrow fibrosis, involving TGFβ1-enhanced fibrocyte activation and immunoregulatory responses. This study might shed new light on the understanding and development of a therapeutic strategy for bone fibrous dysplasia. PMID:26688275

  19. Calcium Sulfate and Platelet-Rich Plasma make a novel osteoinductive biomaterial for bone regeneration

    Directory of Open Access Journals (Sweden)

    Intini Francesco E

    2007-03-01

    Full Text Available Abstract Background With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. Methods First, we tested CS-Platelet in heterotopic (muscle and orthotopic (bone bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. Results The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS-Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. Conclusion This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost-effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments.

  20. Peripheral cannabinoid receptor, CB2, regulates bone mass

    Science.gov (United States)

    Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

    2006-01-01

    The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

  1. Investigations of 90 SR activity concentrations in animal bones in Croatia

    Energy Technology Data Exchange (ETDEWEB)

    Maracic, M.; Franic, Z.; Marovic, G. [Institute for Medical Research and Occupational Health, Zagreb (Croatia)

    2006-07-01

    The paper describes investigations of 90 Sr activity concentrations in long bones of some domestic animals (cows, pigs and lambs) collected over the last ten years in the Republic of Croatia. These investigations are a part of an extended and still ongoing monitoring programme of radioactive contamination of human environment in Croatia. Bone is a critical organ for the accumulation of many radionuclides, including 90 Sr, a highly toxic radionuclide, similar to calcium in its chemicalaviour and metabolic processes. It has been found that the 90 Sr activity concentrations in bones differ between respective animal species, the highest activity concentrations being found in lamb bones. As the decrease of activity concentrations can be generally described by the exponential function, by fitting the measured data to the theoretical curve was estimated the ecological half-life of 90 Sr in bones of respective species. In addition was investigated the relation between 90 Sr activity concentrations in bones and fallout. The transient increases and decreases in 90 Sr activity concentrations in bones can be partially explained by a variety of environmental physical factors that naturally fluctuate. (authors)

  2. Investigations of 90 SR activity concentrations in animal bones in Croatia

    International Nuclear Information System (INIS)

    The paper describes investigations of 90 Sr activity concentrations in long bones of some domestic animals (cows, pigs and lambs) collected over the last ten years in the Republic of Croatia. These investigations are a part of an extended and still ongoing monitoring programme of radioactive contamination of human environment in Croatia. Bone is a critical organ for the accumulation of many radionuclides, including 90 Sr, a highly toxic radionuclide, similar to calcium in its chemical behaviour and metabolic processes. It has been found that the 90 Sr activity concentrations in bones differ between respective animal species, the highest activity concentrations being found in lamb bones. As the decrease of activity concentrations can be generally described by the exponential function, by fitting the measured data to the theoretical curve was estimated the ecological half-life of 90 Sr in bones of respective species. In addition was investigated the relation between 90 Sr activity concentrations in bones and fallout. The transient increases and decreases in 90 Sr activity concentrations in bones can be partially explained by a variety of environmental physical factors that naturally fluctuate. (authors)

  3. Localized CCR2 Activation in the Bone Marrow Niche Mobilizes Monocytes by Desensitizing CXCR4.

    Directory of Open Access Journals (Sweden)

    Hosung Jung

    Full Text Available Inflammatory (classical monocytes residing in the bone marrow must enter the bloodstream in order to combat microbe infection. These monocytes express high levels of CCR2, a chemokine receptor whose activation is required for them to exit the bone marrow. How CCR2 is locally activated in the bone marrow and how their activation promotes monocyte egress is not understood. Here, we have used double transgenic lines that can visualize CCR2 activation in vivo and show that its chemokine ligand CCL2 is acutely released by stromal cells in the bone marrow, which make direct contact with CCR2-expressing monocytes. These monocytes also express CXCR4, whose activation immobilizes cells in the bone marrow, and are in contact with stromal cells expressing CXCL12, the CXCR4 ligand. During the inflammatory response, CCL2 is released and activates the CCR2 on neighboring monocytes. We demonstrate that acutely isolated bone marrow cells co-express CCR2 and CXCR4, and CCR2 activation desensitizes CXCR4. Inhibiting CXCR4 by a specific receptor antagonist in mice causes CCR2-expressing cells to exit the bone marrow in absence of inflammatory insults. Taken together, these results suggest a novel mechanism whereby the local activation of CCR2 on monocytes in the bone marrow attenuates an anchoring signalling provided by CXCR4 expressed by the same cell and mobilizes the bone marrow monocyte to the blood stream. Our results also provide a generalizable model that cross-desensitization of chemokine receptors fine-tunes cell mobility by integrating multiple chemokine signals.

  4. Mean active bone marrow dose to the adult population of the United States from diagnostic radiology

    International Nuclear Information System (INIS)

    Estimates, based on an empirical model and computer program (Ellis, Healy, Shleien and Tucker, HEW publication (FDA)76-8015), have been calculated and are presented on the mean active bone marrow dose to adults from diagnostic radiography, fluoroscopy, and dental radiography as practiced in the United States in 1970. The annual per capita mean active bone marrow dose in 1970 to adults from the above practices is estimated to have been 103 mrad; 77 percent, 20 percent, and 3 percent from radiographic, fluoroscopic and dental examinations, respectively. Examinations of the upper and lower abdomen contribute approximately 39 percent each to the total mean active bone marrow dose for adults; those of the pelvis, 4 percent; the thorax, 12 percent; and head and neck examinations (including dental) contribute about 6 percent. The per capita mean active bone marrow dose for various age groups is discussed. Contributions to the dose within a given age group from different examinations indicate that in the 15 to 34 year age group lumbar and lumbosacral spine examinations contribute most to the mean active bone marrow dose. Thereafter upper Gi series and barium enemas are the highest contributors. Mean active bone marrow doses for children are not estimated in this presentation due to insufficient data. However, the lower rate of use of diagnostic x rays (except dental) in children would reduce the annual per capita mean active bone marrow dose for the entire population to approximately a maximum of 77 mrads. The results may be viewed relative to several surveys of radiation doses from diagnostic radiology performed in other countries which reported annual per capita mean active bone marrow doses varying from 30 to 189 mrads for their entire populations, and with natural background for which the annual per capita whole body and bone marrow dose in the United States is approximately 130 and 86 mrads, respectively

  5. The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice.

    Science.gov (United States)

    Vinik, Yaron; Shatz-Azoulay, Hadas; Vivanti, Alessia; Hever, Navit; Levy, Yifat; Karmona, Rotem; Brumfeld, Vlad; Baraghithy, Saja; Attar-Lamdar, Malka; Boura-Halfon, Sigalit; Bab, Itai; Zick, Yehiel

    2015-01-01

    Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins. PMID:25955862

  6. Dietary Polyphenols, Berries, and Age-Related Bone Loss: A Review Based on Human, Animal, and Cell Studies

    Directory of Open Access Journals (Sweden)

    Patrice A. Hubert

    2014-03-01

    Full Text Available Bone loss during aging has become an increasing public health concern as average life expectancy has increased. One of the most prevalent forms of age-related bone disease today is osteoporosis in which the body slows down bone formation and existing bone is increasingly being resorbed by the body to maintain the calcium balance. Some causes of this bone loss can be attributed to dysregulation of osteoblast and osteoclast activity mediated by increased oxidative stress through the aging process. Due to certain serious adverse effects of the currently available therapeutic agents that limit their efficacy, complementary and alternative medicine (CAM has garnered interest as a natural means for the prevention of this debilitating disease. Natural antioxidant supplementation, a type of CAM, has been researched to aid in reducing bone loss caused by oxidative stress. Naturally occurring polyphenols, such as anthocyanins rich in berries, are known to have anti-oxidative properties. Several studies have been reviewed to determine the impact polyphenol intake—particularly that of berries—has on bone health. Studies reveal a positive association of high berry intake and higher bone mass, implicating berries as possible inexpensive alternatives in reducing the risk of age related bone loss.

  7. Physical activity and bone: The importance of the various mechanical stimuli for bone mineral density. A review

    Directory of Open Access Journals (Sweden)

    Bente Morseth

    2011-08-01

    Full Text Available Numerous studies have reported benefits of regular physical activity on bone mineral density (BMD. The effects of physical activity on BMD are primarily linked to the mechanisms of mechanical loading, but the understanding of the precise mechanism behind the association is incomplete. The aim of this paper was to review the main findings concerning sources and types of mechanical stimuli in relation to BMD. Mechanical forces that act on bone are generated from impact with the ground (ground-reaction forces and from skeletal muscle contractions (muscle forces or muscle-joint forces, but the relative importance of these two sources has not been elucidated. Both muscle-joint forces and gravitational forces seem to be able to induce bone adaptation independently, and there may be differences in the importance of loading sources at different skeletal sites. The nature of the stimuli is affected by the type, intensity, frequency, and duration of the activity. The activity should be dynamic, not static, and the magnitude and rate of the stimuli should be high. In accordance with this, cross-sectional studies report highest BMD in athletes of high-impact activities such as dancing, soccer, volleyball, basketball, squash, speed skating, gymnastics, hockey, and step-aerobics. Endurance activities such as orienteering, skiing, and triathlon seem to be beneficial to a lesser degree, whereas low-impact activities such as swimming and cycling are associated with lower BMD than controls. Both the intensity and frequency of the activity should be varied and increased beyond the habitual level. Duration of the activity seems to be less important, and a few loading cycles seem to be sufficient.

  8. Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

    International Nuclear Information System (INIS)

    Purpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. Methods and Materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D50%) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies

  9. Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

    Energy Technology Data Exchange (ETDEWEB)

    Veres, Cristina; Allodji, Rodrigue S.; Llanas, Damien; Vu Bezin, Jérémi [Radiation Epidemiology Group, Center for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Médicale, UMR 1018, Villejuif (France); Institut Gustave Roussy, Villejuif (France); University Paris-Sud XI, Villejuif (France); Chavaudra, Jean; Mège, Jean Pierre; Lefkopoulos, Dimitri [Institut Gustave Roussy, Villejuif (France); Quiniou, Eric [Institut National de la Santé et de la Recherche Médicale UMR 759, Orsay (France); Deutsh, Eric [Institut Gustave Roussy, Villejuif (France); Institut National de la Santé et de la Recherche Médicale, UMR 1030, Villejuif (France); Vathaire, Florent de [Radiation Epidemiology Group, Center for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Médicale, UMR 1018, Villejuif (France); Institut Gustave Roussy, Villejuif (France); University Paris-Sud XI, Villejuif (France); Diallo, Ibrahima, E-mail: ibrahim.diallo@gustaveroussy.fr [Radiation Epidemiology Group, Center for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Médicale, UMR 1018, Villejuif (France); Institut Gustave Roussy, Villejuif (France); University Paris-Sud XI, Villejuif (France)

    2014-12-01

    Purpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia. Methods and Materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients. Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D{sub 50%}) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean. Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies.

  10. Histone Deacetylases in Bone Development and Skeletal Disorders.

    Science.gov (United States)

    Bradley, Elizabeth W; Carpio, Lomeli R; van Wijnen, Andre J; McGee-Lawrence, Meghan E; Westendorf, Jennifer J

    2015-10-01

    Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn(2+) for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2(+). Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the

  11. In vitro determination of inorganic constituents in bone tissues using neutron activation analysis

    International Nuclear Information System (INIS)

    In the past years, there has been an increasing interest in bone analyses since they are deposits of essential and toxic elements. Besides they have supporting function of human body and protect vital organs. Besides, analyses of inorganic constituents in bones have been carried out to study bone diseases such as osteoporosis and tumors in bones. In this work, an adequate experimental procedure was established for bone tissue treatment, and instrumental neutron activation analysis was applied to trace element determinations in freeze-dried cortical and trabecular tissues and whole bone ash from animal (porcine and bovine) and human ribs. Using short and long-period irradiations at the IEA-R1 nuclear research reactor, the elements Ba, Br, Ca, Cl, Fe, K, Mg, Mn, Na, P, Rb, Sb, Sr and Zn were determined in bone tissues. To validate the analytical methodology, biological certified reference materials were analyzed and their results showed good precision and accuracy. Besides analyses of a bovine rib bone presented precise data for most elements with relative standard deviations lower than 14 %. This result demonstrated that the procedure defined for bone tissue treatment was appropriate to obtain homogeneous samples. However, the calcination was not suitable for whole bone treatment due to loss of Br and Cl. Statistical t test was applied to compare the results obtained for different tissues of bone and also the results found for ribs of two animal species. Comparisons between the results obtained for correspondent tissues of porcine and bovine ribs present different element concentration. Moreover, cortical and trabecular tissues of humans presented different concentrations for all the elements analyzed in this work. These findings indicate that trace elements in bone samples have to be separately studied. (author)

  12. Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction.

    Science.gov (United States)

    Iwamoto, Yoriko; Nishikawa, Keizo; Imai, Ryusuke; Furuya, Masayuki; Uenaka, Maki; Ohta, Yumi; Morihana, Tetsuo; Itoi-Ochi, Saori; Penninger, Josef M; Katayama, Ichiro; Inohara, Hidenori; Ishii, Masaru

    2016-06-01

    Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. PMID:27001307

  13. Effects of Physical Activity and Muscle Quality on Bone Development in Girls

    OpenAIRE

    Joshua N Farr; Laddu, Deepika R.; Blew, Robert M.; Lee, Vinson R.; Going, Scott B.

    2013-01-01

    Poor muscle quality and sedentary behavior are risk factors for metabolic dysfunction in children and adolescents. However, because longitudinal data are scarce, relatively little is known about how changes in muscle quality and physical activity influence bone development.

  14. Osteopenia of Prematurity: Does Physical Activity Improve Bone Mineralization in Preterm Infants?

    Science.gov (United States)

    Stalnaker, Kelsey A; Poskey, Gail A

    2016-01-01

    Bone mineralization of preterm infants is significantly less than full-term infants at birth, placing preterm infants at risk for osteopenia of prematurity and other metabolic bone diseases. Advances in nutritional supplementation and standard nursing care alone have been unsuccessful in improving bone mineralization postnatally. Research supports a daily physical activity protocol of passive range of motion and gentle joint compression when combined with adequate nutritional supplementation reduces osteopenia of prematurity. This article provides a systematic review of the current evidence surrounding early physical activity and neonatal massage for the treatment of osteopenia and indicates the need for universal handling protocols in caring for this unique population. PMID:27052984

  15. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    International Nuclear Information System (INIS)

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  16. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  17. Neural crest-mediated bone resorption is a determinant of species-specific jaw length.

    Science.gov (United States)

    Ealba, Erin L; Jheon, Andrew H; Hall, Jane; Curantz, Camille; Butcher, Kristin D; Schneider, Richard A

    2015-12-01

    Precise control of jaw length during development is crucial for proper form and function. Previously we have shown that in birds, neural crest mesenchyme (NCM) confers species-specific size and shape to the beak by regulating molecular and histological programs for the induction and deposition of cartilage and bone. Here we reveal that a hitherto unrecognized but similarly essential mechanism for establishing jaw length is the ability of NCM to mediate bone resorption. Osteoclasts are considered the predominant cells that resorb bone, although osteocytes have also been shown to participate in this process. In adults, bone resorption is tightly coupled to bone deposition as a means to maintain skeletal homeostasis. Yet, the role and regulation of bone resorption during growth of the embryonic skeleton have remained relatively unexplored. We compare jaw development in short-beaked quail versus long-billed duck and find that quail have substantially higher levels of enzymes expressed by bone-resorbing cells including tartrate-resistant acid phosphatase (TRAP), Matrix metalloproteinase 13 (Mmp13), and Mmp9. Then, we transplant NCM destined to form the jaw skeleton from quail to duck and generate chimeras in which osteocytes arise from quail donor NCM and osteoclasts come exclusively from the duck host. Chimeras develop quail-like jaw skeletons coincident with dramatically elevated expression of TRAP, Mmp13, and Mmp9. To test for a link between bone resorption and jaw length, we block resorption using a bisphosphonate, osteoprotegerin protein, or an MMP13 inhibitor, and this significantly lengthens the jaw. Conversely, activating resorption with RANKL protein shortens the jaw. Finally, we find that higher resorption in quail presages their relatively lower adult jaw bone mineral density (BMD) and that BMD is also NCM-mediated. Thus, our experiments suggest that NCM not only controls bone resorption by its own derivatives but also modulates the activity of mesoderm

  18. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

    OpenAIRE

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; YAMADA, Kumiko; Kubo, Kin-Ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a woode...

  19. Physical activity and lifestyle effects on bone mineral density among young adults: sociodemographic and biochemical analysis.

    Science.gov (United States)

    Alghadir, Ahmad H; Gabr, Sami A; Al-Eisa, Einas

    2015-07-01

    [Purpose] The purpose of this study was to assess the possible role of physical activities, calcium consumption and lifestyle factors in both bone mineral density and bone metabolism indices in 350 young adult volunteers. [Subjects and Methods] All volunteers were recruited for the assessment of lifestyle behaviors and physical activity traits using validated questioners, and bone mineral density (BMD), serum osteocalcin (s-OC), bone-specific alkaline phosphatase (BAP), and calcium were estimated using dual-energy X-ray absorptiometry analysis, and immunoassay techniques. [Results] Male participants showed a significant increase in BMD along with an increase in bone metabolism markers compared with females in all groups. However, younger subjects showed a significant increase in BMD, OC, BAP, and calcium compared with older subjects. Osteoporosis was more common in older subjects linked with abnormal body mass index and waist circumference. Bone metabolism markers correlated positively with BMD, physically activity and negatively with osteoporosis in all stages. Also, moderate to higher calcium and milk intake correlated positively with higher BMD. However, low calcium and milk intake along with higher caffeine, and carbonated beverage consumption, and heavy cigarette smoking showed a negative effect on the status of bone mineral density. Stepwise regression analysis showed that life style factors including physical activity and demographic parameters explained around 58-69.8% of the bone mineral density variation in young adults especially females. [Conclusion] body mass index, physical activity, low calcium consumption, and abnormal lifestyle have role in bone mineral density and prognosis of osteoporosis in young adults. PMID:26311965

  20. A mechanical and histomorphometric analysis of bone bonding by hydroxyapatite-coated strain gages.

    Science.gov (United States)

    Wilson, D L; Szivek, J A; Anderson, P L; Miera, V L; Battraw, G A

    1998-01-01

    Identification of the strains controlling bone remodeling is important for determining ways to prevent bone loss due to load deprivation, or implant placement. Long-term monitoring of strains can potentially provide the best information. Glues are resorbed within 2-3 weeks. Two formulations of microcrystalline hydroxyapatite (HA) were used to attach strain gages to rat femora to assess their long-term in vivo strain measurement capability. Seven male rats received HA-coated gages, and 2 animals underwent a sham procedure. The gages were prepared using a published technique and placed on the antero-lateral aspect of the left femora. After 6-7 weeks, the animals were euthanized and both femora explanted. Gages were attached to the right femora with cyanoacrylate. All femora were tested in cantilever bending, then embedded, sectioned, and stained with mineralized bone stain. The undecalcified sections were examined using transmitted and ultraviolet light microscopy. Mechanical testing showed one HA formulation provided 70-100% bonding. Histology showed intimate contact between the gage and bone surface. Histomorphometry indicated increased bone activity under the gage compared to the remaining bone, the controls, and the shams. The results indicate that microcrystalline HAs bond to bone quickly and can allow long term in vivo measurements. PMID:9659635

  1. Transgenic medaka fish as models to analyze bone homeostasis under micro-gravity conditions in vivo

    Science.gov (United States)

    Winkler, C.; Wagner, T.; Renn, J.; Goerlich, R.; Schartl, M.

    Long-term space flight and microgravity results in bone loss that can be explained by reduced activity of bone-forming osteoblast cells and/or an increase in activity of bone resorbing osteoclast cells. Osteoprotegerin (OPG), a secreted protein of 401 amino acids, has been shown to regulate the balance between osteoblast and osteoclast formation and thereby warrants constant bone mass under normal gravitational conditions. Consistent with this, earlier reports using transgenic mice have shown that increased activation of OPG leads to exc essive bone formation (osteopetrosis), while inactivation of OPG leads to bone loss (osteoporosis). Importantly, it has recently been reported that expression of murine OPG is regulated by vector averaged gravity (Kanematsu et al., 2002, Bone 30, p553). The small bony fish medaka (Oryzias latipes ) has attracted increasing attention as genetic model system to study developmental and pathological processes. To analyze the molecular mechanisms of bone formation in this small vertebrate, we have isolated two related genes, opr-1 and opr -2, from medaka. Our phylogenetic analysis revealed that both genes originated from a common ancestor by fish-specific gene duplication and represent the orthologs of the mammalian OPG gene. Both opr genes are differentially expressed during embryonic and larval development, in adult tissues and in cultured primary osteoblast cells. We have characterized their promoter regions and identified consensus binding sites for transcription factors of the bone-morphogenetic-protein (BMP) p thway and for core-binding-factor-1Aa (cbfa1). Cbfa1 has been shown to be the key regulator of OPG expression during several steps of osteoblast differentiation in mammals. This opens the possibility that the mechanisms controlling bone formation in teleost fish and higher vertebrates are regulated by related mechanisms. We are currently generating transgenic medakafish expressing a GFP reporter gene under control of the

  2. Secondary digital nerve repair in the foot with resorbable p(DLLA-epsilon-CL) nerve conduits

    NARCIS (Netherlands)

    Meek, MF; Nicolai, JPA; Robinson, PH

    2006-01-01

    Nerve guides are increasingly being used in peripheral nerve repair. In the last decade, Much preclinical research has been undertaken into a resorbable nerve guide composed of p(DLLA-epsilon-CL). This report describes the results of secondary digital nerve reconstruction in the foot in a patient wi

  3. Potential bone-inducing activity in vitro of recombinant human bone morphogenetic protein-7 from a CHO expression system

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-yan; SHI Wei-wei; WANG Hao; LI Bo-hua; YANG Yang; TAN Min; XUE Jing-ya; GUO Ya-jun

    2005-01-01

    Objective: To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results:rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.

  4. Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Izabela Podgorski

    2005-03-01

    Full Text Available Prostate cancers metastasize to bone leading to osteolysis. Here we assessed proteolysis of DOcollagen I (a bone matrix protein and, for comparison, DO-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, this degradation was reduced by inhibitors of matrix metallo, serine, cysteine proteases. Because secretion of the cysteine protease cathepsin B is increased in human breast fibroblasts grown on collagen I gels, we analyzed cathepsin B levels and secretion in prostate cells grown on collagen I gels. Levels and secretion were increased only in DU145 cells-cells that expressed the highest baseline levels of cathepsin B. Secretion of cathepsin B was also elevated in DU145 cells grown in vitro on human bone fragments. We further investigated the effect of the bone microenvironment on cathepsin B expression and activity in vivo in a SCID-human model of prostate bone metastasis. High levels of cathepsin B protein and activity were found in DU145, PC3, LNCaP bone tumors, although the PC3 and LNCaP cells had exhibited low cathepsin B expression in vitro. Our results suggest that tumor-stromal interactions in the context of the bone microenvironment can modulate the expression of the cysteine protease cathepsin B.

  5. Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin

    Directory of Open Access Journals (Sweden)

    Jingru Meng

    2016-04-01

    Full Text Available Glucagon-like peptide 1 (GLP-1 plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4 promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased. Furthermore, GLP-1 receptor was detected in bone marrow stromal cells (BMSCs, but not in osteoblast. Activation of GLP-1 receptor by Ex-4 promoted the osteogenic differentiation and inhibited BMSC adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provide a molecular basis for therapeutic potential of GLP-1 against osteoporosis.

  6. Comparison of segmentation using fast marching and geodesic active contours methods for bone

    Science.gov (United States)

    Bilqis, A.; Widita, R.

    2016-03-01

    Image processing is important in diagnosing diseases or damages of human organs. One of the important stages of image processing is segmentation process. Segmentation is a separation process of the image into regions of certain similar characteristics. It is used to simplify the image to make an analysis easier. The case raised in this study is image segmentation of bones. Bone's image segmentation is a way to get bone dimensions, which is needed in order to make prosthesis that is used to treat broken or cracked bones. Segmentation methods chosen in this study are fast marching and geodesic active contours. This study uses ITK (Insight Segmentation and Registration Toolkit) software. The success of the segmentation was then determined by calculating its accuracy, sensitivity, and specificity. Based on the results, the Active Contours method has slightly higher accuracy and sensitivity values than the fast marching method. As for the value of specificity, fast marching has produced three image results that have higher specificity values compared to those of geodesic active contour's. The result also indicates that both methods have succeeded in performing bone's image segmentation. Overall, geodesic active contours method is quite better than fast marching in segmenting bone images.

  7. Effects of Sangu Decoction on Osteoclast Activity in a Rat Model of Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Bo Deng

    2012-01-01

    Full Text Available Bone metastasis (BM is a major clinical problem for which current treatments lack full efficacy. The Traditional Chinese Medicine (TCM Sangu Decoction (SGD has been widely used to treat BM in China. However, no in vivo experiments to date have investigated the effects of TCM on osteoclast activity in BM. In this study, the protective effect and probable mechanism of SGD were evaluated. The model was established using the breast cancer MRMT-1 cells injected into the tibia of rat. SGD was administrated, compared with Zoledronic acid as a positive control. The development of the bone tumor and osteoclast activity was monitored by radiological analysis. TRAP stain was used to identify osteoclasts quantity and activity. TRAP-5b in serum or bone tumor and TRAP mRNA were also quantified. Radiological examination showed that SGD inhibited tumor proliferation and preserved the cortical and trabecular bone structure. In addition, a dramatic reduction of TRAP positive osteoclasts was observed and TRAP-5b levels in serum and bone tumor decreased significantly. It also reduced the mRNA expression of TRAP. The results indicated that SGD exerted potent antiosteoclast property that could be directly related to its TRAP inhibited activity. In addition it prevented bone tumor proliferation in BM model.

  8. Recombinant human bone morphogenetic protein-7 expressed from CHO cells possessing the activity of bone-induced in vitro

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoyan; WANG Hao; YANG Yang; TAN Min; XUE Jingya; NI Haidong; GUO Yajun

    2006-01-01

    Objective To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary (CHO) cells and to establish the in vitro biological activity assay of rhBMP-7. Methods Human BMP-7 cDNA was subcloned into pcDNA3.1 mammalian expression vector and transfected to CHO cells by using the lipofectin transfection method. BMP-7 expression cell culture supernatants were harvested and purified for target protein. To analyze the bioactivity of the secreted rhBMP-7, a novel in vitro assay was established by measuring its alkaline phosphatase (ALP) stimulating of osteoblast cell line, W-20-17. Results BMP-7 stably expressing cell clone was selected, which secreted mature disulfide-linked homodimer form of hBMP-7 and had an apparent molecular weight of 36kDa. rhBMP-7 with >95% purity was obtained using 3 step chromatography method. Bioactivity assay showed that the purified protein specifically stimulated W-20-17 cell producing ALP, with a 4-fold increase of ALP activity at 100ng/ml or more, and the EC50 of 15.6ng/ml. Conclusion Purified rhBMP-7 from this CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates potential bone regeneration activity.

  9. Rehabilitation of resorbed mandibular ridges using mini implant retained overdentures: A case series with 3 year follow-up.

    Science.gov (United States)

    Kumari, Pooja; Verma, Mahesh; Sainia, Vikrant; Gupta, Rekha; Gill, Shubhra

    2016-01-01

    With the increasing average life expectancy of human beings, the need to cater geriatric patients is ever increasing. Complete dentures are an indispensable tool in this regard. The loose and unstable lower complete denture owing to residual ridge resorption is one of the most common problems faced by edentulous patients. Dental implant retained overdentures have emerged as an efficient treatment modality for such patients. Though useful, not every patient is a suitable candidate to go for conventional implant-borne prosthesis, limitation being the available bone width. In such cases, mini implants may be used for augmenting the retention of the dentures and improving the quality of life of patients. In this case series, rehabilitation of three compromised cases with mini implant retained overdentures have been described wherein patients are experiencing instability of lower denture due to thin resorbed mandibular ridges. In one of the cases, three mini implants placed in A, C, and E position were splinted using a cemented bar to retain the mandibular denture. The other two cases were rehabilitated using unsplinted ball type one piece mini implants placed in A, C, and E position in one case and B and D position in another case. Though splinted bar design should be preferred but the lack of available vertical space precluded the utilization of bar in other two cases. The results were found to be satisfactory with no complications reported during a follow-up period of over 3 years in all the cases. PMID:27141177

  10. SHORT-TERM JUMP ACTIVITY ON BONE METABOLISM IN FEMALE COLLEGE-AGED NON-ATHLETES

    Directory of Open Access Journals (Sweden)

    Kohei Kishimoto

    2012-03-01

    Full Text Available There have been few studies examining the short-term effect of high-impact activities on bone metabolism measured by bone serum marker concentrations. The purpose of this study was to examine the effect of short-term high-impact jump activity on bone turnover in female college-aged non-athletes. Twenty six healthy females were randomly assigned to a control or jump group. The subjects jumped 5 days per week for 2 weeks. The participants completed 10 jumps per session. A general health questionnaire and a bone-specific physical activity assessment instrument (BPAQ were completed. BPAQ scores were calculated based on the past history of exercise. Blood draws were taken in both groups before and after the two-week experimental period. The vertical ground reaction force (VGRF of all jumps and jump height were measured for each subject daily and the osteogenic index (OI was measured. Concentrations of serum osteocalcin (OC, Bone Specific Alkaline Phosphatase (BAP, C-Terminal Telopeptides of Type I Collagen (CTX and plasma Tartrate-Resistant Acid Phosphatase (TRAP5b were assessed pre and post jump protocol to measure bone formation and resoprtion respectively. A significant interaction (time x group was found in TRAP5b, and BAP values (p < 0.05. There was a significant decrease in CTX and BAP values in the jump group (p < 0.05 after the two week jump protocol. No significant interactions or changes were observed in OC values for either the jump or the control group. Two weeks of jump activity consisting of 10 jumps/day for 5 days/week with a weekly osteogenic index of 52.6 significantly decreased markers of bone resorption (TRAP5b and CTX and bone formation (BAP in young female non- athletes.

  11. Comparison of circummandibular wiring with resorbable bone plates in pediatric mandibular fractures

    OpenAIRE

    Saikrishna, D.; Gupta, Nimish

    2010-01-01

    Pediatric patients present a unique challenge to maxillofacial surgeons in terms of their treatment planning as well as in their functional and nutritional needs which are different from that of adult patients. Early literature has advocated conservative closed management of pediatric fractures to prevent complications. However recent advances in maxillofacial surgery has enabled us to use biodegradable plates and screws, which overcomes the limitations of metallic plates. We present a compar...

  12. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma.

    Science.gov (United States)

    Yang, J; He, J; Wang, J; Cao, Y; Ling, J; Qian, J; Lu, Y; Li, H; Zheng, Y; Lan, Y; Hong, S; Matthews, J; Starbuck, M W; Navone, N M; Orlowski, R Z; Lin, P; Kwak, L W; Yi, Q

    2012-09-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into severe combined immunodeficient (SCID) or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism-activation of p38 signaling in myeloma cells-by which myeloma cells induce osteolytic bone lesions, and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  13. Formation of acellular cementum-like layers, with and without extrinsic fiber insertion, along inert bone surfaces of aging c-Src gene knockout mice.

    Science.gov (United States)

    Baba, Otto; Miyata, Atsushi; Abe, Tatsuhiko; Shibata, Shunichi; Nakano, Yukiko; Terashima, Tatsuo; Oda, Tsuyoshi; Kudo, Akira; Takano, Yoshiro

    2006-12-01

    To investigate the long-term effects of c-src deficiency on skeletal and dental tissues, we examined the lower jaws and long bones of c-src gene knockout (c-src KO) mice by histological and histochemical methods. Numerous multinucleated osteoclasts were distributed throughout the mandible in 5-wk-old c-src KO mice, but by 14 wk they had almost completely disappeared from the alveolar bone, leaving tartrate-resistant acid phosphatase (TRAP)-positive layers along the bone surface. Deposition of osteopontin-positive mineralized tissue, reminiscent of acellular afibrillar cementum (AAC), was confirmed along the TRAP-positive bone surface at 14 wk. The layer progressively thickened up to 21 months. A comparable mineralized layer was noted along the trabeculae of long bones as thickened cement lines. In the periostin-rich areas of jaw bones, but not in the long bones, portions of AAC-like mineralized layers were often replaced with and/or covered by acellular extrinsic fiber cementum (AEFC)-like tissue. These data suggest that the deposition of AAC-like mineralized tissue is a general phenomenon that may occur along inert or slowly remodeling bone surfaces under conditions characterized by reduced bone-resorbing activity, whereas the induction of AEFC-like tissue seems to be associated with the expression of certain molecules that are particularly abundant in the microenvironment of the periodontal ligament. PMID:17184236

  14. 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. PMID:27463832

  15. Methods for demonstration of enzyme activity in muscle fibres at the muscle/bone interface in demineralized tissue

    DEFF Research Database (Denmark)

    Kirkeby, S; Vilmann, H

    1981-01-01

    A method for demonstration of activity for ATPase and various oxidative enzymes (succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase) in muscle/bone sections of fixed and demineralized tissue has been developed. It was found that it is possible to preserve...... with the aid of a mapping of presence of phosphomonoesterases on bone surfaces, the method may be used to study possible biochemical interactions between bone and muscle tissue at the muscle/bone interface....

  16. Activation of bone remodeling after fatigue: differential response to linear microcracks and diffuse damage.

    Science.gov (United States)

    Herman, B C; Cardoso, L; Majeska, R J; Jepsen, K J; Schaffler, M B

    2010-10-01

    Recent experiments point to two predominant forms of fatigue microdamage in bone: linear microcracks (tens to a few hundred microns in length) and "diffuse damage" (patches of diffuse stain uptake in fatigued bone comprised of clusters of sublamellar-sized cracks). The physiological relevance of diffuse damage in activating bone remodeling is not known. In this study microdamage amount and type were varied to assess whether linear or diffuse microdamage has similar effects on the activation of intracortical resorption. Activation of resorption was correlated to the number of linear microcracks (Cr.Dn) in the bone (R(2)=0.60, pmicrocracks in bone, does not result from sublamellar damage. These findings indicate that inability of diffuse microdamage to activate resorption may be due to lack of a focal injury response. Finally, we found that duration of loading does not affect the remodeling response. In conclusion, our data indicate that osteocytes activate resorption in response to linear microcracks but not diffuse microdamage, perhaps due to lack of a focal injury-induced apoptotic response. PMID:20633708

  17. Reengineering autologous bone grafts with the stem cell activator WNT3A.

    Science.gov (United States)

    Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A

    2015-04-01

    Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. PMID:25682158

  18. Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists.

    Science.gov (United States)

    Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard; Gurven, Michael

    2016-03-01

    Sedentary lifestyle contributes to osteoporosis and fragility fracture risks among modern humans, but whether such risks are prevalent in physically active preindustrial societies with lower life expectancies is unclear. Osteoporosis should be readily observable in preindustrial societies if it was regularly experienced over human history. In this study of 142 older adult Tsimane forager-horticulturalists (mean age ± SD, 62.1 ± 8.6 years; range, 50 to 85 years; 51% female) we used calcaneal quantitative ultrasonography (qUS) to assess bone status, document prevalence of adults with reduced bone status, and identify factors (demographic, anthropometric, immunological, kinesthetic) associated with reduced bone status. Men (23%) are as likely as women (25%) to have reduced bone status, although age-related decline in qUS parameters is attenuated for men. Adiposity and fat-free mass positively co-vary with qUS parameters for women but not men. Leukocyte count is inversely associated with qUS parameters controlling for potential confounders; leukocyte count is positively correlated within adults over time, and adults with persistently low counts have higher adjusted qUS parameters (6% to 8%) than adults with a high count. Reduced bone status characteristic of osteoporosis is common among active Tsimane with minimal exposure to osteoporosis risk factors found in industrialized societies, but with energetic constraints and high pathogen burden. © 2015 American Society for Bone and Mineral Research. PMID:26460548

  19. Dried plum diet protects from bone loss caused by ionizing radiation

    International Nuclear Information System (INIS)

    Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or antiinflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Furthermore, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth

  20. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    Science.gov (United States)

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  1. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    OpenAIRE

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W.; Navone, Nora M.; Orlowski, Robert Z.

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induce...

  2. Physical activity and bone mineral density in Italian middle-aged women

    International Nuclear Information System (INIS)

    Osteoporosis is a major health issue in postmenopausal women on account of the association between low bone mineral density and fractures. A role of physical activity in the prevention and treatment of low bone mineral density is possible but still unclear. The relationship between low spine bone mineral density measured by means of dual photon absorptiometry at lumbar spines, and levels of past and recent physical activity has been assessed by means of a population-based screening study carried out on 1373 women (age 40-64 years) in the North-East of Italy. Physical activity at work and in leisure time was investigated for three specific periods of life: at age 12, between 15 and 19 years (during bone formative years), and in the recent years prior to the interview (30-39 or 50-59 years). Data were analysed comparing low versus high bone mineral density tertile (i.e., 458 and 461 women, respectively), after controlling for other known contributory factors in the development of osteoporosis. A positive association emerged with leisure time physical activity, with significant trends at age 15-19 (odds ratio (OR) for low versus high tertile of leisure time activity: 1.4, 95% confidence interval (CI): 0.8-2.4) and at most recent age (OR: 1.7, 95% CI: 1.1-2.6). Risk trends with occupational physical activity were less clear and non-statistically significant. The present Southern European cross-sectional study lends further support to the possibility that past and recent physical activity helps increasing bone mineral density in middle-aged women. Although the most beneficial type and intensity level of exercise has yet to be determined, the present results provide further evidence that participation in even moderate exercise programs should be encouraged

  3. Chronic osteomyelitis: bone and gallium scan patterns associated with active disease

    International Nuclear Information System (INIS)

    Bone and gallium scans are used to assess osteomyelitis patients with prior bone disease. To refine the criteria for interpreting these scans, the data from 136 consecutive patients with clinically suspected osteomyelitis were reviewed. Active osteomyelitis was diagnosed with surgery or biopsy and culture in 49 patients, excluded with the same criteria in 16, and excluded by clinical follow-up for at least 6 months in 71. Five different scintigraphic patterns were found. The true-positive and false-positive ratios, the likelihood ratios, and posterior probabilities for active osteomyelitis in each pattern were calculated. Only one pattern (gallium uptake exceeding bone-seeking radiopharmaceutical uptake) was indicative of active disease. Other patterns slightly raised or decreased the probability of disease. The extent of these changes varies directly with the prior probability of disease, determined from patient-specific factors (e.g., clinical data, laboratory data, findings on plain films) known best by the referring clinician

  4. Lost salt technique for severely resorbed alveolar ridges: An innovative approach

    Directory of Open Access Journals (Sweden)

    Himanshi Aggarwal

    2012-01-01

    Full Text Available The success of a complete denture relies on the principles of retention, stability and support. The prosthodontist skill lies in applying these principles efficiently in critical situations. Severely resorbed maxillary edentulous ridges that are narrow and constricted with increased inter ridge space provide decreased support, retention and stability. The consequent weight of the processed denture only compromises them further. This article describes a case report of an edentulous patient with resorbed ridges where a simplified technique of fabricating a hollow maxillary complete denture using lost salt technique was used for preservation of denture bearing areas. The hollowing of the denture reduces the weight of the denture, thereby enhancing stability and retention, reducing the further resorption of the jaws.

  5. Antioxidant activity of hydrolysates of deer bone gelatin in a liposome

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yuhong; GAO Tian; ZHANG Ligang

    2007-01-01

    Gelatin extracted from deer bone was hydrolyzed for 3.5-120 min. The degree of hydrolysis was higher from Alcalase-hydrolyzed gelatin than that from neutral proteinase-hydrolyzed gelatin. Alcalase-hydrolyzed gelatin exhibited a stronger antioxidant activity than that of neutral proteinase-hydrolyzed gelatin. Hydrolysates showed strong radical-scavenging ability and Fe2+-chelating activity, both of which were influenced by hydrolysis time. Although nonhydrolyzed gelatin displayed a certain antioxidative effect, it was far less than that of hydrolysates. The hydrolysates of deer bone gelatin can work as a radical stabilizer and metal ion chelator to inhibit lipid oxidation.

  6. Study on osteopotential activity of Terminalia arjuna bark extract incorporated bone substitute

    Indian Academy of Sciences (India)

    G Krithiga; T Hemalatha; R Deepachitra; Kausik Ghosh; T P Sastry

    2014-10-01

    Bark extract of Terminalia arjuna (TA) possesses potent medical properties and therefore, holds a reputed position in both Ayurvedic and Unani systems of medicine. Bone substitutes play an inevitable role in traumatic bone damages. Growth factors induce osteoinductivity, but suffer from limitations such as high cost and side effects. This study aims to evaluate the osteoinductive potential of bark extract of TA in bone substitutes. Bone substitutes prepared with TA bark extract were characterized for their physicochemical properties. In vitro biomineralization study was carried out using simulated body fluid. Cytotoxicity, alkaline phosphatase activity and mineralization potential were assessed using MG-63 cell lines. Scanning electron microscope revealed apatite formation on the surface after biomineralization. Thermogravimetric analysis showed 15% increase in residual weight by deposition of calcium and phosphate and their presence was identified by energy dispersive analysis. Increased alkaline phosphatase and calcium release was observed in bone substitutes prepared with TA extract compared with control. The functional groups of TA bark extract help in in vitro biomineralization. In MG-63 cells, it showed potential influence in cell differentiation. TA extract may be used as low-cost alternative for growth factors for treatment of fractured bones.

  7. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    Science.gov (United States)

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic. PMID:24755526

  8. Comparison of resorbable plates and titanium plates for fixation stability of combined mandibular symphysis and angle fractures

    OpenAIRE

    Lim, Ho-Yong; Jung, Chang-Hwa; Kim, Seong-Yong; Cho, Jin-Yong; Ryu, Jae-Young; Kim, Hyeon-Min

    2014-01-01

    Objectives We compared resorbable plates with titanium plates for treatment of combined mandibular angle and symphyseal fractures. Materials and Methods Patients with mandibular angle and symphysis fractures were divided into two groups. The control (T) group received titanium plates while the experimental (R) group received resorbable plates. All procedures were carried out under general anesthesia using standard surgical techniques. We compared the frequency of wound dehiscence, development...

  9. Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement

    Science.gov (United States)

    Tao, Hu; Hwang, Suk-Won; Marelli, Benedetto; An, Bo; Moreau, Jodie E.; Yang, Miaomiao; Brenckle, Mark A.; Kim, Stanley; Kaplan, David L.; Rogers, John A.; Omenetto, Fiorenzo G.

    2014-01-01

    A paradigm shift for implantable medical devices lies at the confluence between regenerative medicine, where materials remodel and integrate in the biological milieu, and technology, through the use of recently developed material platforms based on biomaterials and bioresorbable technologies such as optics and electronics. The union of materials and technology in this context enables a class of biomedical devices that can be optically or electronically functional and yet harmlessly degrade once their use is complete. We present here a fully degradable, remotely controlled, implantable therapeutic device operating in vivo to counter a Staphylococcus aureus infection that disappears once its function is complete. This class of device provides fully resorbable packaging and electronics that can be turned on remotely, after implantation, to provide the necessary thermal therapy or trigger drug delivery. Such externally controllable, resorbable devices not only obviate the need for secondary surgeries and retrieval, but also have extended utility as therapeutic devices that can be left behind at a surgical or suturing site, following intervention, and can be externally controlled to allow for infection management by either thermal treatment or by remote triggering of drug release when there is retardation of antibiotic diffusion, deep infections are present, or when systemic antibiotic treatment alone is insufficient due to the emergence of antibiotic-resistant strains. After completion of function, the device is safely resorbed into the body, within a programmable period. PMID:25422476

  10. Biodegradable Polymers in Bone Tissue Engineering

    OpenAIRE

    Govaert, Leon E.; Smit, Theo H; Robert J. Kroeze; Helder, Marco N.

    2009-01-01

    The use ofdegradable polymers in medicine largely started around the mid 20th century with their initial use as in vivo resorbing sutures. Thorough knowledge on this topic as been gained since then and the potential applications for these polymers were, and still are, rapidly expanding. After improving the properties of lactic acid-based polymers, these were no longer studied only from a scientific point of view, but also for their use in bone surgery in the 1990s. Unfortunately, after implan...

  11. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    OpenAIRE

    Trouvin, Anne-Priscille; Goëb, Vincent

    2010-01-01

    Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG) and receptor activator for nuclear factor-κB (RANK) ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, ...

  12. PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact

    Energy Technology Data Exchange (ETDEWEB)

    Klaeser, Bernd; Wartenberg, Jan; Weitzel, Thilo; Krause, Thomas [Bern University Hospital and University of Bern, Department of Nuclear Medicine, Inselspital, Bern (Switzerland); Wiskirchen, Jakub [Bern University Hospital and University of Bern, Department of Nuclear Medicine, Inselspital, Bern (Switzerland); University Hospital Tuebingen, Department of Radiology, Neuroradiology, and Nuclear Medicine, Tuebingen (Germany); Schmid, Ralph A. [Bern University Hospital and University of Bern, Department of Thoracic Surgery, Inselspital, Bern (Switzerland); Mueller, Michel D. [Bern University Hospital and University of Bern, Department of Obstetrics and Gynaecology, Inselspital, Bern (Switzerland)

    2010-11-15

    In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions. We retrospectively reviewed the data of 20 consecutive patients who underwent multimodal image-guided bone biopsies using a dedicated PET/CT system in a step-by-step technique. Technical and clinical success rates of PET/CT-guided biopsies were evaluated. Questionnaires were sent to the referring physicians to assess the impact of biopsies on patient management and to check the clinical need for PET/CT-guided biopsies. Clinical indications for biopsy were to histologically verify the aetiology of metabolically active bone lesions without a morphological correlate confirming the suspicion of metastases in 15 patients, to determine the origin of suspected metastases in 3 patients and to evaluate the appropriateness of targeted therapy options in 2 patients. Biopsies were technically successful in all patients. In 19 of 20 patients a definite histological diagnosis was possible. No complications or adverse effects occurred. The result of PET/CT-guided bone biopsies determined a change of the planned treatment in overall 56% of patients, with intramodality changes, e.g. chemotherapy with palliative instead of curative intent, and intermodality changes, e.g. systemic therapy instead of surgery, in 22 and 50%, respectively. PET/CT-guided bone biopsies are a promising alternative to conventional techniques to make metabolically active bone lesions - especially without a distinctive morphological correlate - accessible for histological verification. PET/CT-guided biopsies had a major clinical impact in patients who otherwise cannot be reliably stage grouped at the time of treatment decisions. (orig.)

  13. Lipopolysaccharide-activated microglial-induced neuroglial cell differentiation in bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Xiaoguang Luo; Chunlin Ge; Yan Ren; Hongmei Yu; Zhe Wu; Qiushuang Wang; Chaodong Zhang

    2008-01-01

    BACKGROUND: Microglia are very sensitive to environmental changes, often becoming activated by pathological conditions. Activated microglia can exert a dual role in injury and repair in various diseases of the central nervous system, including cerebral ischemia, Parkinson's disease, and Alzheimer's disease. OBJECTIVE: An immortal microglial cell line, BV2, was treated with varying concentrations of lipopolysaccharide (LPS) to induce a pathological situation. Supernatant was harvested and incubated with bone marrow mesenchymal stem cells and, concomitantly, bone marrow mesenchymal stem cell differentiation was observed. DESIGN: A controlled observation, in vitro experiment. SETTING: Department of Neurology, First Affiliated Hospital of China Medical University. MATERIALS: Five male 2-3-week-old Sprague Dawley rats were purchased from Animal Laboratory Center of China Medical University and included in this study. The protocol was performed in accordance with ethical guidelines for the use and care of animals. The microglial cell line BV2 was produced by Cell Research Institute of Chinese Academy of Sciences. LPS was produced by Sigma Company, USA. METHODS: This study was performed in the Central Laboratory of China Medical University from September 2006 to March 2007. Rat femoral and tibial bone marrow was collected for separation and primary culture of bone marrow mesenchymal stem cells. Bone marrow mesenchymal stem cell cultures were divided into 5 groups: control group, non-activated group, as well as low-, medium-, and high-dose LPS groups. In the control group, bone marrow mesenchymal stem cells were cultured with Dulbecco's modified Eagle's medium (DMEM) supplemented with fetal bovine serum (volume fraction 0.1). In the non-activated group, bone marrow mesenchymal stem cells were incubated with non-activated BV2 supernatant. In the low-, medium-, and high-dose LPS groups, bone marrow mesenchymal stem cells were incubated with LPS (0.01, 0.1 and 1

  14. Enzymatically synthesized inorganic polymers as morphogenetically active bone scaffolds: application in regenerative medicine.

    Science.gov (United States)

    Wang, Xiaohong; Schröder, Heinz C; Müller, Werner E G

    2014-01-01

    In recent years a paradigm shift in understanding of human bone formation has occurred that starts to change current concepts in tissue engineering of bone and cartilage. New discoveries revealed that fundamental steps in biomineralization are enzyme driven, not only during hydroxyapatite deposition, but also during initial bioseed formation, involving the transient deposition and subsequent transformation of calcium carbonate to calcium phosphate mineral. The principal enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase, open novel targets for pharmacological intervention of bone diseases like osteoporosis, by applying compounds acting as potential activators of these enzymes. It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future. PMID:25376489

  15. The use of bone scintigraphy to detect active Hansen's disease in mutilated patients

    International Nuclear Information System (INIS)

    Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2). Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided. (orig.)

  16. Hydrogen sulfide and sodium nitroprusside compete to activate/deactivate MMPs in bone tissue homogenates

    Directory of Open Access Journals (Sweden)

    Vacek TP

    2013-03-01

    Full Text Available Thomas P Vacek, Natia Qipshidze, Suresh C Tyagi Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, USA Background: Bone microvascular remodeling is the primary predictor of bone structure and function. Remodeling by its very nature implies synthesis and degradation of the extracellular matrix. Normally, 50% of total protein in the vessel wall is elastin. During remodeling, elastin is degraded by specialized matrix metalloproteinases (MMPs. Because the turnover of elastin is 1000-fold slower than that of collagen, most of the elastin is replaced by stiffer collagen. Stiffer vessels impose pressure on the aortic valve, causing regurgitation and increased pulse pressure. On the other hand, high MMP activity will cause vascular dilatation, leading to aneurysm. Therefore, balanced constitutive remodeling is necessary for adequate bone structure and function. Interestingly, collagen-degrading MMPs are involved in various pathological conditions, including osteoporosis, osteoarthritis, and cardiovascular disease. Sodium nitroprusside is a nitric oxide donor that could potentially alter MMP activity via vasodilation in vivo, but can also produce peroxynitrite, which activates MMPs by combining with superoxide. Moreover, hydrogen sulfide is a known antioxidant as well as a vasodilator, and is also speculated to contribute directly to MMP activity. We hypothesized that hydrogen sulfide reduced activity of MMP in ex vivo bone tissue homogenates and that sodium nitroprusside would increase MMP activity in vitro. Methods: We surgically removed the tibia and femur from anesthetized mice, and prepared bone tissue homogenates using a mortar and pestle, measured the protein concentration with a spectrophotometer, and detected MMP activity using gelatin gel zymography. Results: Our data showed increased MMP activity at a sodium nitroprusside concentration of 1 µM, and MMP activity increased exponentially. There

  17. Vancomycin graft composite for infected bone defects

    International Nuclear Information System (INIS)

    Reconstructive surgery under septic conditions represents a major challenge in orthopaedics. Local application of antibiotics can provide high drug levels at the site of infection without systemic effects. However, removal of non-resorbable implants and filling of defects usually requires additional operative procedures. An ideal antibiotic carrier should provide for : 1) Effective bactericidal activity, especially against staphylococci including MRSA; 2) High and long lasting levels at the site of infection without local or systemic toxicity; 3) Repair of defects without a second stage procedure. Allogeneic cancellous bone is proven to be effective in restoration of bone stock. Vancomycin is effective against all gram-positive populations and the agent of choice for infections with MRSA. The aim of our study is to investigate the efficacy of a combination of both components in bone infection. Cancellous bone of human origin was processed during several steps and incubated in 10% vancomycin solution. The antimicrobial activity of the vancomycin graft composite (VGC) was evaluated using an agar diffusion bioassay against staphylococcus aureus and high performance liquid chromatography (HPLC). The testing period was up to 9 weeks. Elution of vancomycin from the graft was evaluated in 2.5% human albumin solution, which was exchanged every 24 hours. Concentration of vancomycin in allograft-bone was between 6.653[tg/g and 23.194gg/g with an average of 15.250 [tg/g, which is equivalent to 10.000 times the minimum inhibitory concentration (MIC) for s. aureus. The initial activity decreased to approx. 50% during the first week and approx. 30% at the end of the 9th week. The lowest values measured exceeded the MIC by 2000 times. Concentration in surrounding fluid decreased from 24.395,80 to 18,43pg/ml after 11 complete exchanges. Human cancellous bone, processed in an adequate way, offers capability to store high quantities of vancomycin. Vancomycin graft composites are

  18. Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases.

    Science.gov (United States)

    Wan, Xinhai; Corn, Paul G; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W; Efstathiou, Eleni; Li Ning Tapia, Elsa M; Tapia, Elsa M Li-Ning; Zurita, Amado J; Aparicio, Ana; Ravoori, Murali K; Vazquez, Elba S; Robinson, Dan R; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M; Logothetis, Christopher J; Navone, Nora M

    2014-09-01

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell-bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. PMID:25186177

  19. Prostate Cancer Cell–Stromal Cell Cross-Talk via FGFR1 Mediates Antitumor Activity of Dovitinib in Bone Metastases

    Science.gov (United States)

    Wan, Xinhai; Corn, Paul G.; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W.; Efstathiou, Eleni; Li-Ning Tapia, Elsa M.; Zurita, Amado J.; Aparicio, Ana; Ravoori, Murali K.; Vazquez, Elba S.; Robinson, Dan R.; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K.; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M.; Logothetis, Christopher J.; Navone, Nora M.

    2015-01-01

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell–bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. PMID:25186177

  20. Correlation between low bone density and disease activity in patients with ulcerative colitis.

    Science.gov (United States)

    Amiriani, Taghi; Besharat, Sima; Pourramezan, Zahra; Mirkarimi, Honey Sadat; Aghaei, Mehrdad; Joshaghani, Hamidreza; Roshandel, Gholamreza; Faghani, Maryam; Besharat, Mahsa

    2015-01-01

    BACKGROUND Different clinical and epidemiological studies using dual-energy X-ray absorptiometry have shown an increased prevalence of low bone mineral density in patients with inflammatory bowel diseases. The aim of this study was to assess the correlation between bone density and the disease activity in patients with ulcerative colitis. METHODS In this cross-sectional study, 52 patients with ulcerative colitis (duration of the disease less than 5 years) were invited to our research center, Golestan province, northeast of Iran, during February 2012 up to August 2012. A demographic checklist and Simple Clinical Colitis Activity Index was completed for each patients and 5 cc of blood sample was taken after obtaining the informed consent. We used colorimetry method for measuring serum calcium, UV method for serum phosphorus and ELISA for serum vitamin D. Dual-energy X-ray absorptiometry was done to evaluate the bone density. Data analysis was done using SPSS software version 16. Normality of data was assessed using Kolmogorov- Smirnov test. T and ANOVA tests were used if data had normal distribution. Mann-Whitney U or Kruskal-Wallis tests were used for the remaining data. Correlation between qualitative variables was evaluated by Chi-square test. RESULTS The mean (±SD) age and disease activity of the patients were 37.72 (±12.18) years and 4.78 (±1.98), respectively. There were no correlation between disease activity and mean age. Low bone density was seen in 30.8%, 11.5%, and 15.4% in spine, femur neck, and hip, respectively. There was no relationship between Z-score of total hip, spine, and femur neck with disease activity, age, and duration of disease (p>0.05). CONCLUSION Our results showed an acceptable rate of low bone density in patients with ulcerative colitis without any correlation with the disease activity index. PMID:25628850

  1. Correlation Between Low Bone Density and Disease Activity in Patients with Ulcerative Colitis

    Science.gov (United States)

    Amiriani, Taghi; Besharat, Sima; Pourramezan, Zahra; Mirkarimi, Honey Sadat; Aghaei, Mehrdad; Joshaghani, Hamidreza; Roshandel, Gholamreza; Faghani, Maryam; Besharat, Mahsa

    2015-01-01

    BACKGROUND Different clinical and epidemiological studies using dual-energy X-ray absorptiometry have shown an increased prevalence of low bone mineral density in patients with inflammatory bowel diseases. The aim of this study was to assess the correlation between bone density and the disease activity in patients with ulcerative colitis. METHODS In this cross-sectional study, 52 patients with ulcerative colitis (duration of the disease less than 5 years) were invited to our research center, Golestan province, northeast of Iran, during February 2012 up to August 2012. A demographic checklist and Simple Clinical Colitis Activity Index was completed for each patients and 5 cc of blood sample was taken after obtaining the informed consent. We used colorimetry method for measuring serum calcium, UV method for serum phosphorus and ELISA for serum vitamin D. Dual-energy X-ray absorptiometry was done to evaluate the bone density. Data analysis was done using SPSS software version 16. Normality of data was assessed using Kolmogorov– Smirnov test. T and ANOVA tests were used if data had normal distribution. Mann-Whitney U or Kruskal-Wallis tests were used for the remaining data. Correlation between qualitative variables was evaluated by Chi-square test. RESULTS The mean (±SD) age and disease activity of the patients were 37.72 (±12.18) years and 4.78 (±1.98), respectively. There were no correlation between disease activity and mean age. Low bone density was seen in 30.8%, 11.5%, and 15.4% in spine, femur neck, and hip, respectively. There was no relationship between Z-score of total hip, spine, and femur neck with disease activity, age, and duration of disease (p>0.05). CONCLUSION Our results showed an acceptable rate of low bone density in patients with ulcerative colitis without any correlation with the disease activity index. PMID:25628850

  2. Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis

    NARCIS (Netherlands)

    Hofkens, Wouter; Grevers, Lilyanne C.; Walgreen, Birgitte; de Vries, Teun J.; Leenen, Pieter J. M.; Everts, Vincent; Storm, Gert; van den Berg, Wim B.; van Lent, Peter L.

    2011-01-01

    The objective of this study was to determine the effect of systemic delivery of prednisolone phosphate (PLP) encapsulated within long circulating 'stealth' liposomes on bone erosion and osteoclast activity during experimental antigen-induced arthritis (AIA). Liposomal PLP strongly suppressed knee jo

  3. ACE inhibitory activity of pangasius catfish (Pangasius sutchi) skin and bone gelatin hydrolysate

    OpenAIRE

    Mahmoodani, Fatemeh; Ghassem, Masomeh; Babji, Abdul Salam; Yusop, Salma Mohamad; Khosrokhavar, Roya

    2012-01-01

    Skin and bone gelatins of pangasius catfish (Pangasius sutchi) were hydrolyzed with alcalase to isolate Angiotensin Converting Enzyme (ACE) inhibitory peptides. Samples with the highest degree of hydrolysis (DH) were separated into different fractions with molecular weight cut-off (MWCO) sizes of 10, 3 and 1 kDa, respectively and assayed for ACE inhibitory activity. Skin and bone gelatins had highest DH of 64.87 and 68.48 % after 2 and 1 h incubation, respectively. Results from this study ind...

  4. Neutron activation analysis of NBS oyster tissue (SRM 1566) and IAEA animal bone (H-5)

    International Nuclear Information System (INIS)

    Instrumental and radiochemical neutron activation analysis (INAA and RNAA) were employed to measure about 37 major, minor, and trace elements in two standard reference materials: oyster tissue (SRM 1566) supplied by the National Bureau of Standards (NBS) and animal bone (H-5) supplied by the International Atomic Energy Agency (IAEA). Wherever the comparison exists, the data show excellent agreement with accepted values for each SRM. These SRM's are useful as reference standards for the analysis of biological materials. Additionally, the chondritic normalized rare earth element pattern of animal bone behaves as a smooth function of the ionic radii, as previously observed for biological materials. 7 references, 2 figures, 2 tables

  5. Combined Percutaneous Iliosacral Screw Fixation With Sacroplasty Using Resorbable Calcium Phosphate Cement for Osteoporotic Pelvic Fractures Requiring Surgery.

    Science.gov (United States)

    Collinge, Cory A; Crist, Brett D

    2016-06-01

    Osteoporotic sacral fractures, including acute and chronic insufficiency fractures, are increasing in frequency and present a number of management problem. Many of these patients are treated nonoperatively with relative immobility (eg, bedrest, wheelchair, or weight-bearing restrictions) and analgesics, which likely make the osteoporotic component worse. Surgery in this patient population may be desirable in some cases with the goals of improving mobility, relieving pain, and healing in an aligned position while minimizing deformity progression. However, internal fixation of the osteoporotic pelvis can be difficult. Large unicortical lag screws are the workhorse of posterior pelvic fixation, and yet fixation in cancellous bone corridors of an osteoporotic sacrum seems unlikely to achieve optimal fixation. As a result, the operative management and clinical results of these difficult injuries may not be uniformly successful. The authors present a technique for treating osteoporotic patients with a sacral fracture when operative treatment is indicated using percutaneous screw fixation combined with screw augmentation using a resorbable calcium phosphate bone substitute or "cement." The guide wire for a 7.3-mm or other large cannulated lag screw is fully inserted along the desired bony sacral corridor as is standard. The lag screw is then inserted over the wire to the depth where cement is desired. The guide wire is removed, and the aqueous calcium phosphate is injected through the screw's cannulation. For acute fractures, cement was applied to the areas distant to the fracture; whereas in insufficiency fractures, the cement was inserted along most of the screw path. The guide wire then can be reinserted and the lag screw fully inserted. The rationale for using these 2 modalities is their synergistic effect: the cannulated screw provides typical screw fixation and also a conduit for cement application. The cement augments the lag screw's purchase in osteoporotic bone

  6. How Does Physical Activity Help Build Healthy Bones?

    Science.gov (United States)

    ... weight-bearing physical activities include: Walking, jogging, or running Playing tennis or racquetball Playing field hockey Climbing stairs Jumping rope and other types of jumping Playing basketball Dancing Hiking Playing soccer Lifting weights Swimming and bicycling are not weight- ...

  7. Dual mode antibacterial activity of ion substituted calcium phosphate nanocarriers for bone infections

    Directory of Open Access Journals (Sweden)

    Sampath Kumar eT.S.

    2015-05-01

    Full Text Available Nanotechnology has tremendous potential for the management of infectious diseases caused by multi-drug resistant (MDR bacteria, through the development of newer antibacterial materials and efficient modes of antibiotic delivery. Calcium phosphate (CaP bioceramics are commonly used as bone substitutes due to their similarity to bone mineral and are widely researched upon for the treatment of bone infections associated with bone loss. CaPs can be used as local antibiotic delivery agents for bone infections and can be substituted with antibacterial ions in their crystal structure to have a wide spectrum, sustained antibacterial activity even against drug resistant bacteria. In the present work, a dual mode antibiotic delivery system with antibacterial ion substituted calcium deficient hydroxyapatite (CDHA nanoparticles has been developed. Antibacterial ions such as zinc, silver and strontium have been incorporated into CDHA at concentrations of 6 at. %, 0.25-0.75 at. % and 2.5-7.5 at. % respectively. The samples were found to be phase pure, acicular nanoparticles of length 40-50 nm and width 5-6 nm approximately. The loading and release profile of doxycycline, a commonly used antibiotic, was studied from the nanocarriers. The drug release was studied for five days and the release profile was influenced by the ion concentrations. The release of antibacterial ions was studied over a period of 21 days. The ion substituted CDHA samples were tested for antibacterial efficacy on S.aureus and E.coli by MIC/MBC studies and time-kill assay. AgCDHA and ZnCDHA showed high antibacterial activity against both bacteria while SrCDHA was weakly active against S.aureus. Present study shows that the antibiotic release can provide the initial high antibacterial activity and the sustained ion release can provide a long-term antibacterial activity. Such dual mode antibiotic and antibacterial ion release offers an efficient and potent way to treat an incumbent drug

  8. Calcitonin receptors as markers for osteoclastic differentiation: correlation between generation of bone-resorptive cells and cells that express calcitonin receptors in mouse bone marrow cultures.

    Science.gov (United States)

    Hattersley, G; Chambers, T J

    1989-09-01

    The osteoclast is the cell that resorbs bone. It is known to derive from hemopoietic precursors, but analysis of lineage and regulation of differentiation has been hampered by lack of a specific marker that enables identification of cells of osteoclastic phenotype. Previously used markers, such as multinuclearity, that are specific for osteoclasts in bone become less specific in culture. Uniquely among bone and bone marrow cells, osteoclasts possess abundant calcitonin (CT) receptors. We therefore tested the correlation between the generation of bone-resorptive function and the formation of CT receptor-positive cells from hemopoietic tissue in vitro. Without 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3], a hormone that induces osteoclastic differentiation in vitro, bone marrow cultures showed very little bone resorption, and only small numbers of CT receptor-positive cells developed. When 1,25-(OH)2D3 was added to the cultures, CT receptor-positive cells developed within 1 day and reached a peak after 7 days. Bone resorption commenced within 2 days of hormone addition. There was a strong parallelism between the cumulative number of CT receptor-positive cells and the extent of bone resorption. The capacity of cultures to generate bone-resorptive activity and CT receptor-positive cells declined progressively when 1,25-(OH)2D3 was added to hemopoietic tissue after a 7- to 21-day hormone-free incubation period. The number of CT receptor-positive cells in these cultures correlated strongly (r = 0.96) with bone resorption. The behavior of these cultures suggests that 1,25-(OH)2D3 acts to induce terminal differentiation of osteoclast precursors present in the cultures, and that precursor cell numbers decreased with increasing time in vitro. All of the CT receptor-positive cells in control cultures and all of those seen shortly after 1,25-(OH)2D3 addition were mononuclear, despite considerable bone resorption; the majority of CT receptor-positive cells remained mononuclear

  9. Trace elements determination in human bone tissue by neutron activation analysis

    International Nuclear Information System (INIS)

    Determination of trace elements in human bones is of the great interest for evaluating nutritional state and for prevention, control and study of several diseases caused by mineral or trace element imbalance. In this study, neutron activation analysis (NAA) was applied for trace elements in human rib bone tissue. Elements Ba, Br, Ca, Cl, Fe, K, Mg, Mn, Na, P, Rb, Sr and Zn were determined in total bone tissue and in its subcompartments (cortical and trabecular tissue) separately. Irradiations were performed at IEA-R1 nuclear research reactor of IPEN-CNEN/SP. Short irradiations of 4 minutes were carried out under thermal neutron flux of 4.5x1011 n cm-2 s-1 and long irradiations of 16 hours under neutron flux of 1012 n cm-2 s-1. Results obtained showed a variability between elemental concentrations found for bones from different individuals. A comparative study made between the data obtained for cortical and trabecular bones indicated that these two tissues present different elemental concentrations. Concentrations of Ca, Mg, Na and P obtained for cortical tissue were the same magnitude of those published data. (author)

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

    OpenAIRE

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

    2014-01-01

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

  11. Mycobacterium tuberculosis Contaminant Risk on Bone Marrow Aspiration Material from Iliac Bone Patients with Active Tuberculous Spondylitis

    OpenAIRE

    Ahmad Jabir Rahyussalim; Tri Kurniawati; Andriansjah Rukmana

    2016-01-01

    There was a concern on Mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. This research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. As many as nine patients with tuberculous spondylitis were used as samples. During the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria c...

  12. Three-Dimensional Bone Regeneration of Alveolar Ridge Defects Using Corticocancellous Allogeneic Block Grafts: Histologic and Immunohistochemical Analysis.

    Science.gov (United States)

    Jun, Choong-Man; Yun, Jeong-Ho

    2016-01-01

    In this study, the effectiveness of a corticocancellous block allograft for restoring alveolar ridge defects in preparation for the placement of dental implants was assessed. Significant ridge defects in four partially edentulous patients were reconstructed using an irradiated corticocancellous allogeneic block soaked in platelet-rich plasma, which was also covered with a resorbable collagen membrane. After 5 or 6 months, the sites were reentered and a trephine bone core specimen was obtained from each augmented site for histologic, histomorphometric, and immunohistochemical assessment. In all four cases, histologic evaluation of the augmented site showed areas of new vital bone formation around the graft material (mean newly formed bone fraction, 23.7%; mean total mineralized tissue fraction, 40.1%), in which osteocytes were frequently observed within the lacunae. Immunohistochemical analysis showed the presence of biomarkers commonly related to active bone formation (alkaline phosphatase, osteocalcin, and bone morphogenetic protein-2), confirming that the biochemical environment was conducive to new bone formation. The findings of this study demonstrate that the use of allogeneic block grafts for restoring alveolar ridge defects prior to the placement of dental implants may be an effective and advantageous alternative to autograft procedures. PMID:26697555

  13. Activity in the gastrointestinal tract after administration of bone-seeking radiopharmaceuticals. Experimental studies in mice

    International Nuclear Information System (INIS)

    Purpose: To test the possibility that (radio)activity of non-pertechnetate nature is excreted into the gastrointestinal tract at bone scintigraphy. Material and Methods: The distribution of a bone-seeking radiopharmaceutical (99mTc-HDP) was studied in an experimental mouse system by dissecting different organs and assessing their activity with a gamma-counter. Results: A comparison of the activity of the submandibular glands, which are assumed to accumulate only pertechnetate, and the gastrointestinal tract showed that a significant fraction of the activity excreted into the gastrointestinal tract did not consist of pertechnetate. Part of the excretion took place in the stomach. It was not connected to a specific bone-seeking agent or 99Mo/99mTc generator. Nor did it increase with time between make-up and injection. The excretion of the non-pertechnetate activity was reduced by cimetidine and omeprazole. These gastric-secretion blocking drugs did not reduce excretion of pertechnetate or significantly affect the general distribution of the radiopharmaceutical. Conclusion: There is a significant excretion of non-pertechnetate activity in the gastrointestinal tract. Part of this may be caused by excretion of the undegraded radiopharmaceutical by the stomach mucosa. (orig.)

  14. Relationships between ESR-evaluated doses estimated from enamel and activity of radionuclides in bone and teeth of reindeer

    International Nuclear Information System (INIS)

    Doses of radiation estimated from ESR analysis of tooth enamel were compared with activities of alpha- and beta-emitters in enamel and in bone tissue of mandibles of 77 reindeer from populations with different levels of radiation contamination. Contribution of the radionuclides incorporated into bone (or bone-seeking radionuclides in food) to ESR-evaluated doses was substantial and the contribution of the radionuclides incorporated into enamel itself proved to be relatively small

  15. Prostate Cancer Cell–Stromal Cell Cross-Talk via FGFR1 Mediates Antitumor Activity of Dovitinib in Bone Metastases

    OpenAIRE

    Wan, Xinhai; Corn, Paul G.; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W.; Efstathiou, Eleni; Li-Ning Tapia, Elsa M.; Zurita, Amado J.; Aparicio, Ana; Ravoori, Murali K.; Vazquez, Elba S; Robinson, Dan R.; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K

    2014-01-01

    Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially medi...

  16. Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors

    Science.gov (United States)

    Yamagishi, Tetsuro; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Sasaki, Taro; Hatano, Hiroshi; Hotta, Tetsuo; Endo, Naoto

    2016-01-01

    The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts. PMID:27163152

  17. Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021.

    Science.gov (United States)

    Ruan, Alexandra; Tobin, Nicole H; Mulligan, Kathleen; Rollie, Adrienne; Li, Fan; Sleasman, John; Aldrovandi, Grace M

    2016-08-01

    Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss. PMID:26885808

  18. Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

    International Nuclear Information System (INIS)

    Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERαColII, expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERαColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERαColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERαColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  19. The mean active bone marrow dose to the adult population of the United States from diagnostic radiology

    International Nuclear Information System (INIS)

    Based on an empirical dosimetry model, estimates have been calculated and are presented on the mean active bone marrow dose to adults from diagnostic radiography, fluoroscopy, and dental radiography, as practiced in the United States in 1970. The annual per capita mean active bone marrow dose to adults in 1970 from the above practices is estimated to have been 103 mrad: 77, 20 and 3% form radiographic, fluoroscopic and dental examinations respectively. The per capita mean active bone marrow dose for various age groups is discussed. Contributions to the dose within a given age group from different examinations indicate that in the 15-34-yr age group, lumbar and lumbosacral spine examinations contribute most to the mean active bone marrow dose; thereafter, upper GI series and barium enemas are the highest contributors. Mean active bone marrow doses for children have not been estimated because of insufficient data. However, the lower rate of use of diagnostic X-rays (except dental) in children would reduce the annual per capita mean active bone marrow dose for the entire population to a maximum of approximately 77 mrad. In 1964 the annual per capita mean active bone marrow dose to adults is estimated to have been 83 mrad. A comparison of the results with surveys of radiation doses from diagnostic radiology performed in other countries and with natural radiation background is described. (author)

  20. Mycobacterium tuberculosis Contaminant Risk on Bone Marrow Aspiration Material from Iliac Bone Patients with Active Tuberculous Spondylitis

    Directory of Open Access Journals (Sweden)

    Ahmad Jabir Rahyussalim

    2016-01-01

    Full Text Available There was a concern on Mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. This research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. As many as nine patients with tuberculous spondylitis were used as samples. During the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria culture, and PCR (polymerase chain reaction tests for Mycobacterium tuberculosis at the Clinical Microbiology Laboratory of Faculty of Medicine Universitas Indonesia. This research showed that there was a relationship between diagnostic confirmation of tuberculous spondylitis based on the PCR test and bacterial culture on the solid vertebral lesion material with the PCR test and bacterial culture from the bone marrow aspirates. If the diagnostic confirmation concluded positive results, then there was a higher probability that there would be a positive result for the bone marrow aspirates, so that it was not recommended to use autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis unless the PCR and culture examination of the bone marrow showed a negative result.

  1. Mycobacterium tuberculosis Contaminant Risk on Bone Marrow Aspiration Material from Iliac Bone Patients with Active Tuberculous Spondylitis.

    Science.gov (United States)

    Rahyussalim, Ahmad Jabir; Kurniawati, Tri; Rukmana, Andriansjah

    2016-01-01

    There was a concern on Mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. This research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. As many as nine patients with tuberculous spondylitis were used as samples. During the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria culture, and PCR (polymerase chain reaction) tests for Mycobacterium tuberculosis at the Clinical Microbiology Laboratory of Faculty of Medicine Universitas Indonesia. This research showed that there was a relationship between diagnostic confirmation of tuberculous spondylitis based on the PCR test and bacterial culture on the solid vertebral lesion material with the PCR test and bacterial culture from the bone marrow aspirates. If the diagnostic confirmation concluded positive results, then there was a higher probability that there would be a positive result for the bone marrow aspirates, so that it was not recommended to use autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis unless the PCR and culture examination of the bone marrow showed a negative result. PMID:27294117

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

    Directory of Open Access Journals (Sweden)

    Marion David

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

  3. Nmp4/CIZ suppresses the response of bone to anabolic parathyroid hormone by regulating both osteoblasts and osteoclasts.

    Science.gov (United States)

    Childress, Paul; Philip, Binu K; Robling, Alexander G; Bruzzaniti, Angela; Kacena, Melissa A; Bivi, Nicoletta; Plotkin, Lilian I; Heller, Aaron; Bidwell, Joseph P

    2011-07-01

    How parathyroid hormone (PTH) increases bone mass is unclear, but understanding this phenomenon is significant to the improvement of osteoporosis therapy. Nmp4/CIZ is a nucleocytoplasmic shuttling transcriptional repressor that suppresses PTH-induced osteoblast gene expression and hormone-stimulated gains in murine femoral trabecular bone. To further characterize Nmp4/CIZ suppression of hormone-mediated bone growth, we treated 10-week-old Nmp4-knockout (KO) and wild-type (WT) mice with intermittent human PTH(1-34) at 30 μg/kg daily or vehicle, 7 days/week, for 2, 3, or 7 weeks. Null mice treated with hormone (7 weeks) gained more vertebral and tibial cancellous bone than WT animals, paralleling the exaggerated response in the femur. Interestingly, Nmp4/CIZ suppression of this hormone-stimulated bone formation was not apparent during the first 2 weeks of treatment. Consistent with the null mice enhanced PTH-stimulated addition of trabecular bone, these animals exhibited an augmented hormone-induced increase in serum osteocalcin 3 weeks into treatment. Unexpectedly, the Nmp4-KO mice displayed an osteoclast phenotype. Serum C-terminal telopeptide, a marker for bone resorption, was elevated in the null mice, irrespective of treatment. Nmp4-KO bone marrow cultures produced more osteoclasts, which exhibited elevated resorbing activity, compared to WT cultures. The expression of several genes critical to the development of both osteoblasts and osteoclasts was elevated in Nmp4-KO mice at 2 weeks, but not 3 weeks, of hormone exposure. We propose that Nmp4/CIZ dampens PTH-induced improvement of trabecular bone throughout the skeleton by transiently suppressing hormone-stimulated increases in the expression of proteins key to the required enhanced activity and number of both osteoblasts and osteoclasts. PMID:21607813

  4. Microcracks and osteoclast resorption activity in vitro.

    Science.gov (United States)

    Rumpler, Monika; Würger, Tanja; Roschger, Paul; Zwettler, Elisabeth; Peterlik, Herwig; Fratzl, Peter; Klaushofer, Klaus

    2012-03-01

    During bone remodeling osteoclasts resorb bone, thus removing material, e.g., damaged by microcracks, which arises as a result of physiological loading and could reduce bone strength. Such a process needs targeted bone resorption exactly at damaged sites. Osteocytic signaling plays a key role in this process, but it is not excluded that osteoclasts per se may possess toposensitivity to recognize and resorb damaged bone since it has been shown that resorption spaces are associated with microcracks. To address this question, we used an in vitro setup of a pure osteoclast culture and mineralized substrates with artificially introduced microcracks and microscratches. Histomorphometric analyses and statistical evaluation clearly showed that these defects had no effect on osteoclast resorption behavior. Osteoclasts did not resorb along microcracks, even when resorption started right beside these damages. Furthermore, quantification of resorption on three different mineralized substrates, cortical bone, bleached bone (bone after partial removal of the organic matrix), and dentin, revealed lowest resorption on bone, significantly higher resorption on bleached bone, and highest resorption on dentin. The difference between native and bleached bone may be interpreted as an inhibitory impact of the organic matrix. However, the collagen-based matrix could not be the responsible part as resorption was highest on dentin, which contains collagen. It seems that osteocytic proteins, stored in bone but not present in dentin, affect osteoclastic action. This demonstrates that osteoclasts per se do not possess a toposensitivity to remove microcracks but may be influenced by components of the organic bone matrix. PMID:22271249

  5. Osteoblastogenesis and Role of Osteoblasts in Calcıum Homeostasis and Remodeling of Bone

    Directory of Open Access Journals (Sweden)

    Neslihan Başcıl Tütüncü

    2008-05-01

    Full Text Available Bone remodeling is very important for repair of microfractures and fatigue damage and prevention of excessive aging and its consequences. Bone remodeling lasts for about 6-9 months. During this period osteoclasts resorb damaged bone and osteoblasts synthesize new bone. The lifespan of mature osteoclasts is about 15 days and for osteoblasts 3 months. Therefore, the time required for the remodeling of a given segement of bone is much longer than the lifespan of its cells which perform remodeling. A supply of new osteoblasts and osteoclasts are therefore needed for succesful remodeling by the basic multicellular unit. The major event that triggers osteogenesis is the transition of mesenchymal stem cells into bone differentiating osteoblast cells. Osteoblast commitment and differentation are controlled by complex activities. Many factors are involved in the regulation of osteoblastogenesis. Bone morphogenetic proteins and the Wnt glycoproteins play crucial roles in signaling osteoblast commitment and differentiation, and are the only known factors capable of initiating osteoblastogenesis from uncommitted progenitors. They can initiate commitment of mesenchymal cells to osteoblastic lineage. The initial cell division is asymmetric, giving rise to another stem cell and a committed osteoprogenitor. After commitment to the osteoblastic lineage, a osteoprogenitor cell gives rise to the transit-amplifying compartment. At this stage osteoprogenitor cells proliferate intensively. After this stage, the cells are more differentiated and give rise to preosteoblasts which express both STRO1, alkaline phosphatase, pyrophosphate, and type 1 collagen. Preosteoblasts are committed to the osteoblast lineage with extensive replicative capacity, but have no self-renewal capacity. Preosteoblasts form the intermediate stage of osteoblastogenesis. The mature osteoblasts express osteopontin, alkaline phosphatase, bone sialoprotein, and osteocalcin. This stage is

  6. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express uPAR and...... to mechanical tests. UPAR KO calvaria osteoblasts were characterized by proliferation assays, RT-PCR for important proteins secreted during differentiation, and immunoblot for activator protein 1 (AP-1) family members. In vitro osteoclast formation was tested with uPAR KO bone marrow monocytes in the...... osteoblasts showed a proliferative advantage with no difference in apoptosis, higher matrix mineralization, and earlier appearance of alkaline phosphatase (ALP). Surface RANKL expression at different stages of differentiation was not altered. AP-1 components, such as JunB and Fra-1, were upregulated in u...

  7. Mutant activated FGFR3 impairs endochondral bone growth by preventing SOX9 downregulation in differentiating chondrocytes.

    Science.gov (United States)

    Zhou, Zi-Qiang; Ota, Sara; Deng, Chuxia; Akiyama, Haruhiko; Hurlin, Peter J

    2015-03-15

    Fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the control of endochondral ossification, and bone growth and mutations that cause hyperactivation of FGFR3 are responsible for a collection of developmental disorders that feature poor endochondral bone growth. FGFR3 is expressed in proliferating chondrocytes of the cartilaginous growth plate but also in chondrocytes that have exited the cell cycle and entered the prehypertrophic phase of chondrocyte differentiation. Achondroplasia disorders feature defects in chondrocyte proliferation and differentiation, and the defects in differentiation have generally been considered to be a secondary manifestation of altered proliferation. By initiating a mutant activated knockin allele of FGFR3 (FGFR3K650E) that causes Thanatophoric Dysplasia Type II (TDII) specifically in prehypertrophic chondrocytes, we show that mutant FGFR3 induces a differentiation block at this stage independent of any changes in proliferation. The differentiation block coincided with persistent expression of SOX9, the master regulator of chondrogenesis, and reducing SOX9 dosage allowed chondrocyte differentiation to proceed and significantly improved endochondral bone growth in TDII. These findings suggest that a proliferation-independent and SOX9-dependent differentiation block is a key driving mechanism responsible for poor endochondral bone growth in achondroplasia disorders caused by mutations in FGFR3. PMID:25432534

  8. Optimization of administrated activity for patients submitted to bone scintillography

    International Nuclear Information System (INIS)

    One of the consequences of the use of radioactive tracers in medical routine is that some radiation is delivered to both the pt and the occupationally exposed workers. It is indeed necessary to optimise the technique aiming to reduce AA, but still obtaining acceptable information density and good image quality. We qualitatively evaluated images obtained from 125 pts who benefited from conventional BS (99mTc-MDP). Images were qualified by a nuclear physician and by a physicist working in a nuclear medicine department. Pts were divided into 3 groups: G1 (n=40, aged 23-85 yo, AA ranging from 1036-1110 MBq); G2 (n=46, aged 20-84 yo, AA ranging from 888-999 MBq) and G3 (n=39, aged 24-94 yo, AA ranging from 740-850 MBq Images were classified (good, G; fair, F; poor, P). We also evaluated the index of body mass (IBM), age (A) and the time of image acquisition (T). The percentage of images classified as G, F and P in the different groups was as follows: G1 - G=35; F=47,5; P=17,5; G2 - G=24, F=45,6, P=30,5; G3 - 33,3, F=46, P=20,5). No significant difference was found among the images classified as a) G in groups 1 and 3, b) F in the 3 groups, c) P in groups 1 and 3. As expected, the quality of image correlated negatively with A and the IBM in the 3 groups. T of acquisition was as follows in the different groups: G1 = 19 ± 4, G2 = 22 ± 5, G3 = 25 ± 5 (significantly different between G1 and G3). Further studies with larger series of pts are needed, but we believe that it is possible to reduce the AA to 740-850 MBq per pt when conventional BS is performed without a reduction in the quality of the image. Elder pts and those with high IMB could be injected with higher activities. (author)

  9. Circulating cytokeratin 18 fragments and activation of dormant tumor cells in bone marrow of cancer patients

    OpenAIRE

    Ausch, Christoph; Buxhofer-Ausch, Veronika; Olszewski, Ulrike; Hamilton, Gerhard

    2010-01-01

    In cancer patients detection of systemic disease is of great importance to obtain prognostic information and to guide therapy. Bone marrow (BM) seems to be a common homing tissue for the early spread of tumor cells from various epithelial tumors; however, verification of the prognostic significance of BM-disseminated tumor cells (BM-DTCs), is restricted to breast cancer so far. These cells may be dormant for a long time, and signals triggering their activation leading to recurrence remain to ...

  10. The effects of Zinc supplementation on serum zinc, alkaline phosphatase activity and fracture healing of bones

    International Nuclear Information System (INIS)

    Objective was to determine the effect of zinc supplementation on callus information, serum zinc and alkaline phosphatase activity in humans. This randomized, double-blind, placebo controlled clinical trial was conducted on 60 patients with traumatic bone fracture referred to Shohada Hospital of Tabriz, Iran from August to December 2007. Subjects were randomly divided into 2 groups: cases (n=30), receiving one capsule of zinc sulfate consists of 50 mg zinc each day and the controls (n=30), receiving placebo for 60 days. Individual and clinical information was determined by a questionnaire: nutritional intake by 3 days food records at the beginning and the end of trial. Serum zinc and alkaline phosphatase was measured by atomic absorption spectroscopy and by enzymatic method. Callus information during fracture healing was evaluated by radiography of the bone. There was no significant difference in physical activity, gender, age, type of fractures and nutrient intake, between the 2 groups. The administration of zinc caused a significant elevation of serum zinc and alkaline phosphatase activity. Assessment of bone x-rays showed a significant progress in callus formation in cases compared to the controls. This study shows that zinc supplementation can stimulate fracture healing, however, it needs further study. (author)

  11. Osteoprotegerin in bone metastases: mathematical solution to the puzzle.

    Directory of Open Access Journals (Sweden)

    Marc D Ryser

    Full Text Available Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes.

  12. Physical Activity and Bone Health%体力活动与骨健康

    Institute of Scientific and Technical Information of China (English)

    李红娟; 王正珍; 严翊

    2012-01-01

    The present study aims to review the progress and trend of the research concerning physical activity and bone health with Dr.Wolffe memorial lecture in the 59th ACSM annual meeting as the breakthrough point.Evidence-based research provides moderate evidence for the positive role of physical activity in improving bone health and preventing osteoporosis fracture.The Wolff Law and the Mechanostat lay the theory foundation for the positive effect of physical activity in improving bone health.But there is lack of strong evidence in the clinical guidance of the physical activity in preventing osteoporosis.It′s necessary to expand Mechanostat theory and explore it′s mechanism through multi-discipline research.Multi-disciplinary and multi-type research was conducted to discuss mechanical load mechanism of the function of physical activity on bones and its metabolizing effect.It also conducted the research on the effect of different types of exercises on bone metabolize and effective exercise load of different groups of people.Multi-center randomized controlled trial for years would be the best way to get strong evidence for the role of physical activity in health promotion.%以2012年ACSM第59届年会Dr.Wolffe纪念讲座为切入点,对体力活动与骨骼健康的研究进展及未来发展趋势进行综述。循证研究表明:体力活动有益骨健康和预防骨质疏松性骨折,证据等级为中等,Wolff定律、机械负荷理论等为体力活动促进骨健康奠定了理论基础。但现有预防骨质疏松的体力活动临床指南还缺乏强有力的证据支持,必须进一步拓展和深入研究机械负荷理论,从多学科、多层次探讨体力活动作用于骨骼的机械负荷机制和代谢影响;开展不同运动方式对骨代谢的影响及不同人群有效运动负荷的研究;通过多中心的随机对照试验,可为体力活动促进骨健康提供更多更有力的证据支持。

  13. Estimation of kidney and bladder radionuclide activity for patients undergoing bone scan

    Directory of Open Access Journals (Sweden)

    Luc T. Bambara

    2015-07-01

    Full Text Available Radionuclide activities in the kidney and bladder have been estimated experimentally from practical data 3 h after injection of Tc-99m MDP, using conjugate view methodology. The study involved sixty-five patient images from the database of a nuclear medicine department in Ghana. Time–activity curve was stimulated with MatLab computer program using biokinetic model published in MIRD Report 13. The model was used to determine theoretical activities in kidney and bladder, which were compared with the experimental data. Estimated radionuclide activities for the kidney and bladder were both minimal in the experimental case comparative to the theoretical. The fraction of injected activity in kidney and bladder were less than 1% of injected activity, and hence kidney and bladder could be seen to receive very low doses during bone scans.

  14. Determination of the most appropriate stress distribution by Finite Element Analysis in fixation with resorbable screws after Bilateral Sagittal Split Ramus Osteotomy surgery

    Directory of Open Access Journals (Sweden)

    Sarkarat F.

    2009-12-01

    Full Text Available "nBackground and Aim: Due to the complications associated with fixation by Titanium screws and plates in Bilateral Sagittal Split Ramus Osteotomy (BSSRO surgery, the use of resorbable polymers has been increasingly recommended. Since there are not enough studies on this issue, this study aimed to assess the most appropriate stress distribution in fixation with resorbable screws after BSSRO surgery by Fnite Element Analysis (FEA."nMaterials and Methods: This experimental study was performed on simulated human mandible using Ansys and Catia softwares. The osteotomy line was applied to the simulated model and experimental loads of 75, 135 and 600 N were respectively exerted according to the natural direction of occlusal force. The distribution pattern of stress was assessed and compared for fixation with one resorbable screw, two resorbable screws in vertical pattern, two resorbable screws in horizontal pattern, three resorbable screws in L pattern and three resorbable screws in inverted backward L pattern using Ansys software."nResults: Among the four simulated fixations, L pattern showed the highest primary stability. Two screws in vertical pattern were also associated with sufficient primary stability and less trauma and cost for patients. One screw did not provide enough stability under 600 N."nConclusion: Polymer-based resorbable screws (polyglycolic acid and D, L polylactide acid provided satisfactory primary stability in BSSRO surgery.

  15. In vivo analysis of bone calcium by local neutron activation of the hand. Results osteoporotic and hemodialysed patients

    International Nuclear Information System (INIS)

    Neutron activation analysis can be used to measure the total bone mass or simply the calcium mass or concentration of a bone segment, for example the hand bones or vertebrae. For a number of reason, dosimetric, technological but especially physiophatological we decided to use local activation technique. In generalized demineralising one diseases, particularly osteoporosis, the calcium content variations of one segment are in fast comparable to those of another, and more generally to the mineral content variations of the whole skeleton. It is true that ideally we should measure the mineral content of the lumbar vertebrae where the metabolic activity is especially high, and where damage may occur sooner or in any case is detected earlier in osteoporosis. However neutron irradiation of the vertebrae meets with certain technical problems and may also present difficulties in the interpretation of results. Furthermore in other bone diseases, hyperparathyroidism for instance and especially renal osteodystrophy, bone mineral loss is particularly premature and pronounced in the hand and we therefore decided for the moment to use the hand for the neutron activation analysis of bone calcium. The technique enabled us to measure the calcium concentration of the hand bones in hemodialysed subjects and in patients with primitive osteoporosis

  16. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation.

    Science.gov (United States)

    Ming, Wei; Lu, Gan; Xin, Sha; Huanyu, Lu; Yinghao, Jiang; Xiaoying, Lei; Chengming, Xu; Banjun, Ruan; Li, Wang; Zifan, Lu

    2016-08-01

    Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. PMID:27237975

  17. Bone mineral density changes during pregnancy in actively exercising women as measured by quantitative ultrasound

    OpenAIRE

    To, William W. K.; Wong, Margaret W. N.

    2012-01-01

    Objective To evaluate whether bone mineral density (BMD) changes in women engaged in active exercises during pregnancy would be different from non-exercising women. Methods Consecutive patients with singleton pregnancies who were engaged in active exercise training during pregnancy were prospectively recruited over a period of 6 months. Quantitative USG measurements of the os calcis BMD were performed at 14–20 weeks and at 36–38 weeks. These patients were compared to a control cohort of non-e...

  18. Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway

    OpenAIRE

    Guo-yong Yu; Gui-zhou Zheng; Bo Chang; Qin-xiao Hu; Fei-xiang Lin; De-zhong Liu; Chu-cheng Wu; Shi-xin Du; Xue-dong Li

    2016-01-01

    Naringin is a major flavonoid found in grapefruit and is an active compound extracted from the Chinese herbal medicine Rhizoma Drynariae. Naringin is a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of naringin involves the Notch signaling pathway. Rat bone marrow stromal cells (BMSCs) were cultured in osteogenic ...

  19. The teleost fish medaka ( Oryzias latipes) as genetic model to study gravity dependent bone homeostasis in vivo

    Science.gov (United States)

    Wagner, T. U.; Renn, J.; Riemensperger, T.; Volff, J.-N.; Köster, R. W.; Goerlich, R.; Schartl, M.; Winkler, C.

    2003-10-01

    Long-term space flight and microgravity result in bone loss that can be explained by reduced activity of bone-forming cells (osteoblasts) and/or an increase in activity of bone resorbing cells (osteoclasts). Osteoprotegerin (OPG) has been shown to regulate the balance between osteoblast and osteoclast cell numbers and is involved in maintaining constant bone mass under normal gravitational conditions. The small bony fish medaka ( Oryzias latipes) has attracted increasing attention as a genetic model system to study normal embryonic developmental and pathological processes. To analyze the molecular mechanisms of bone formation in this small vertebrate, we have isolated two opg genes, opgl and opg2, from medaka. Our phylogenetic analysis reveals that both genes originated from a common ancestor by fish-specific gene duplication and represent the orthologs of the mammalian opg gene. Both opg genes are differentially expressed during embryonic and larval development, in adult tissues and in cultured primary osteoblast-like cells. Furthermore, we have characterized the opg2 promoter region and identified consensus binding sites for the transcription factor core-binding-factor-1A (CBFA1). In mammals, CBFA1 has been shown to be a regulator of opg expression and to be essential for several steps during osteoblast differentiation. Here we show that sequence and expression domains of opg, cbfal and a member of the dlx gene family are highly conserved between medaka and higher vertebrates. This suggests that not only single genes but entire genetic networks for bone formation are conserved between teleosts and mammals. These findings will open medaka fish as a genetic model to monitor bone formation under different gravity conditions in a living whole animal allowing the identification of novel factors involved in bone homeostasis.

  20. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com; Jiang, Shengdan, E-mail: jiangsd@126.com; Jiang, Leisheng, E-mail: leisheng_jiang@126.com

    2014-08-15

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.

  1. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

    International Nuclear Information System (INIS)

    Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) and bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss

  2. Bone microdamage and cell apoptosis

    Directory of Open Access Journals (Sweden)

    Noble B.

    2003-12-01

    Full Text Available Accumulation of microdamage in bone leads to the reduced strength of our skeleton. In health, bone adapts to the prevailing mechanical needs of the organism and is also capable of self-repair, sensing, removing and replacing damaged or mechanically insufficient volumes of bone. In disease and old age these characteristics are reduced. In order to undertake both of the processes of functional adaptation and repair the bone resorbing and forming cells must be very accurately targeted to areas of physiological need. The mechanism by which cells are precisely targeted to areas requiring repair is both clinically relevant and poorly understood. The osteocyte has been assumed to play a role in sensing damage and signaling for its removal, due largely to its abundance throughout the mineralized bone matrix. However, until recently there has been little evidence that osteocyte function is modified in the vicinity of the microdamage. Here I outline the possibility that the targeted removal of bone containing microcracks might involve signals derived from the apoptotic death of the osteocyte. I shall discuss data that support or refute this view and will consider the possible molecular mechanisms by which controlled cell death might contribute to the signals for repair in the light of work involving cells in bone and other tissue systems.

  3. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia

    Science.gov (United States)

    Chinnasamy, Dhanalakshmi; Yu, Zhiya; Morgan, Richard A.; Lee, Chyi-Chia Richard; Restifo, Nicholas P.

    2013-01-01

    Fibroblast activation protein (FAP) is a candidate universal target antigen because it has been reported to be selectively expressed in nearly all solid tumors by a subset of immunosuppressive tumor stromal fibroblasts. We verified that 18/18 human tumors of various histologies contained pronounced stromal elements staining strongly for FAP, and hypothesized that targeting tumor stroma with FAP-reactive T cells would inhibit tumor growth in cancer-bearing hosts. T cells genetically engineered with FAP-reactive chimeric antigen receptors (CARs) specifically degranulated and produced effector cytokines upon stimulation with FAP or FAP-expressing cell lines. However, adoptive transfer of FAP-reactive T cells into mice bearing a variety of subcutaneous tumors mediated limited antitumor effects and induced significant cachexia and lethal bone toxicities in two mouse strains. We found that FAP was robustly expressed on PDGFR-α+, Sca-1+ multipotent bone marrow stromal cells (BMSCs) in mice, as well as on well-characterized, clinical-grade multipotent human BMSCs. Accordingly, both mouse and human multipotent BMSCs were recognized by FAP-reactive T cells. The lethal bone toxicity and cachexia observed after cell-based immunotherapy targeting FAP cautions against its use as a universal target. Moreover, the expression of FAP by multipotent BMSCs may point toward the cellular origins of tumor stromal fibroblasts. PMID:23712432

  4. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ryosuke [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Kayamori, Kou [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Oue, Erika [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Sakamoto, Kei [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Harada, Kiyoshi [Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan)

    2015-03-20

    Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

  5. Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

  6. The Inhibitory Effects of Forsythia Koreana Extracts on the Metastatic Ability of Breast Cancer Cells and Bone Resorption by Osteoclasts

    Science.gov (United States)

    Kim, Yu Li; Lee, Sun Kyoung; Park, Kwang-Kyun; Chung, Won-Yoon

    2016-01-01

    Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor β1-induced migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts. PMID:27390737

  7. Total body irradiation for installment of arylsulfatase B activity in a cat by bone marrow transplantation

    International Nuclear Information System (INIS)

    Mucopolysaccharidosis VI is an inherited, metabolic defect in which a deficiency of arylsulfatase B, results in accumulation of glycosaminoglycans (GAG) in lysosomes. Arylsulfatase B activity was installed in an affected 2 year old siamese cat with no arylsulfatase B activity, excess urinary GAG, Alder-Reilly bodies in neutrophils, facial dysmorphia, corneal clouding, multiple epiphyseal dysplasia, and hind limb paresis. Following grafting of bone marrow from an immunologically nonreactive, female sibling with normal arylsulfatase B activity, increased arylsulfatase B activity and urinary excretion of hexuronic acid decreased by 19 days post transplantation. There were no metachromatic inclusions in circulating neutrophils, which were phenotypically female. The cat now has competent trilineage hematopoiesis, resolution of the facial dysmorphia, no corneal clouding, and improved movement of the head, neck, and mandible. The technique, sequence of hematologic recovery, and evidence of engraftment, are discussed. This may be a model for correction of mucopolysaccharidosis VI in man

  8. Salvation of a severely resorbed mandibular ridge with a neutral zone technique

    Directory of Open Access Journals (Sweden)

    Kanhaiya L Gupta

    2011-01-01

    Full Text Available The objective of any prosthodontic service is to restore the patient to normal function, contour, esthetics, speech, and health. An optimum denture stability is difficult to achieve in conventional complete dentures. This problem is more magnified in mandibular dentures. The design of prostheses to replace lost teeth and resorbed ridges is largely determined by the position and amount of morphological change in the denture-bearing area of the jaws. A neutral zone may be defined as the space where, during function, the forces of the lips and cheeks pressing inward neutralize the forces of the tongue pressing outward. The neutral zone concept implies acquired muscle control, especially by tongue, lips, and cheeks toward the denture stability. Advocates of the neutral zone concept agree that a lack of favorable leverage is observed when teeth are positioned directly over the ridge. By employing the neutral zone concept, the dislodging muscle energy can easily become a retentive and stabilizing force.

  9. Bio resorbability of the modified hydroxyapatite in Tris-HCL buffer

    Science.gov (United States)

    Golovanova, O. A.; Izmailov, R. R.; Ghyngazov, S. A.

    2016-02-01

    The solubility of carbonated hydroxyapatite powders and granulated carbonated hydroxyapatite produced from the synovial biofluid model solution has been studied. The kinetic characteristics of dissolution were determined. It was found that the solubility of carbonated hydroxyapatite is higher as compared to that of hydroxyapatite. The impact of the organic matrix on the rate of sample dissolution was revealed. For HA-gelatin composites, as the gelatin concentration grows, the dissolution rate becomes greater, and a sample of 6.0 g / L concentration has higher resorbability. The results of the research can be used to study the kinetics of dissolution and the biocompatibility of ceramic materials for medicine, namely for reconstructive surgery, dentistry, and development of drug delivery systems.

  10. Novel targets of vitamin D activity in bone: action of the vitamin D receptor in osteoblasts, osteocytes and osteoclasts.

    Science.gov (United States)

    Ryan, Jackson W; Reinke, Daniel; Kogawa, Masakazu; Turner, Andrew G; Atkins, Gerald J; Anderson, Paul H; Morris, Howard A

    2013-12-01

    The active form of vitamin D, 1,25-dihydroxyvitamin D3, carries out its diverse range of biological activities by binding to the nuclear vitamin D receptor, present in almost every cell of the body. It is well established that adequate serum 25-hydroxyvitamin D levels correlate with a reduction in the incidence of osteoporosis; however, the physiological basis for this relationship remains elusive. Although, the endocrine actions of vitamin D are thoroughly appreciated, the effect of vitamin D on bone tissue and bone cells is yet to be completely understood. There exists a wealth of literature that suggests the VDR within the three major bone cell types, osteoblasts, osteocytes and osteoclasts, is responsible for the regulation of bone homeostasis. The circumstances, under which the action of 1,25-dihydroxyvitamin D3 elicits an anabolic or catabolic role have not been elucidated. However, it would seem that vitamin D can evoke both of these effects and that this is partly mediated by calcium homeostasis. This raises the possibility that dietary calcium intake and vitamin D metabolism act concomitantly at the kidney, intestine and the bone in a coordinated response. Thus, to maintain adequate bone homeostasis and reduce the risk of metabolic bone disease via the diet, it is important to consider this duality of vitamin D action in relation to the overall calcium economy. PMID:24010964

  11. Determinants of bone marrow adiposity: the modulation of peroxisome proliferator-activated receptor-γ2 activity as a central mechanism.

    Science.gov (United States)

    Sadie-Van Gijsen, H; Hough, F S; Ferris, W F

    2013-10-01

    Although the presence of adipocytes in the bone marrow is a normal physiological phenomenon, the role of these cells in bone homeostasis and during pathological states has not yet been fully delineated. As osteoblasts and adipocytes originate from a common progenitor, with an inverse relationship existing between osteoblastogenesis and adipogenesis, bone marrow adiposity often negatively correlates with osteoblast number and bone mineral density. Bone adiposity can be affected by several physiological and pathophysiological factors, with abnormal, elevated marrow fat resulting in a pathological state. This review focuses on the regulation of bone adiposity by physiological factors, including aging, mechanical loading and growth factor expression, as well as the pathophysiological factors, including diseases such as anorexia nervosa and dyslipidemia, and pharmacological agents such as thiazolidinediones and statins. Although these factors regulate bone marrow adiposity via a plethora of different intracellular signaling pathways, these diverse pathways often converge on the modulation of the expression and/or activity of the pro-adipogenic transcription factor peroxisome proliferator-activated receptor (PPAR)-γ2, suggesting that any factor that affects PPAR-γ2 may have an impact on the fat content of bone. PMID:23800517

  12. Bone structure and quality preserved by active versus passive muscle exercise in 21 days tail-suspended rats

    Science.gov (United States)

    Luan, Huiqin; Sun, Lian-wen; Fan, Yu-bo

    2012-07-01

    Humans in Space suffer from microgravity-induced attenuated bone strength that needs to be addressed by on-orbit exercise countermeasures. However, exercise prescriptions so far did not adequately counteract the bone loss of astronauts in spaceflight because even active muscle contractions were converted to passive mode during voluntary bouts. We tested our hypothesis in unloaded rat hind limb following twenty-one days of tail-suspension (TS) combined with exercise using a hind limb stepper device designed by our group. Female Sprague Dawley rats (250g b.wt.) were divided into four groups (n=5, each): TS-only (hind limb unloading), TS plus passive mode exercise (TSP) induced by mechanically-forced passive hind limb lifting, TS plus active mode exercise (TSA) entrained by plantar electrostimulation, and control (CON) group. Standard measures of bone (e.g., mineral density, trabecular microstructure, biomechanics and ash weight) were monitored. Results provided that the attenuated properties of unloaded hind limb bone in TS-rats were more effectively supported by active mode than by passive mode motions. We here propose a modified exercise regimen combined with spontaneous muscle contractions thereby considering the biodynamic demands of both muscle and bone during resistive-load exercise in microgravity. Keywords: rat, BMD, DXA, passive exercise, active exercise, bone loss, tail suspension, spaceflight analogue, exercise countermeasure.

  13. A Bone Anabolic Effect of RANKL in a Murine Model of Osteoporosis Mediated Through FoxP3+ CD8 T Cells.

    Science.gov (United States)

    Buchwald, Zachary S; Yang, Chang; Nellore, Suman; Shashkova, Elena V; Davis, Jennifer L; Cline, Anna; Ko, Je; Novack, Deborah V; DiPaolo, Richard; Aurora, Rajeev

    2015-08-01

    TNF-α and IL-17 secreted by proinflammatory T cells (T(EFF)) promote bone erosion by activating osteoclasts. We previously demonstrated that in addition to bone resorption, osteoclasts act as antigen-presenting cells to induce FoxP3 in CD8 T cells (Tc(REG)). The osteoclast-induced regulatory CD8 T cells limit bone resorption in ovariectomized mice (a murine model of postmenopausal osteoporosis). Here we show that although low-dose receptor activator of NF-κB ligand (RANKL) maximally induces Tc(REG) via Notch signaling pathway to limit bone resorption, high-dose RANKL promotes bone resorption. In vitro, both TNF-α and IL-17, cytokines that are abundant in ovariectomized animals, suppress Tc(REG) induction by osteoclasts by repressing Notch ligand expression in osteoclasts, but this effect can be counteracted by addition of RANKL. Ovariectomized mice treated with low-dose RANKL induced Tc(REG) that suppressed bone resorption, decreased T(EFF) levels, and increased bone formation. High-dose RANKL had the expected osteolytic effect. Low-dose RANKL administration in ovariectomized mice lacking CD8 T cells was also osteolytic, confirming that Tc(REG) mediate this bone anabolic effect. Our results show that although RANKL directly stimulates osteoclasts to resorb bone, it also controls the osteoclasts' ability to induce regulatory T cells, engaging an important negative feedback loop. In addition to the conceivable clinical relevance to treatment of osteoporosis, these observations have potential relevance to induction of tolerance and autoimmune diseases. PMID:25656537

  14. Trace element determination in human bones using the neutron activation analysis method

    International Nuclear Information System (INIS)

    This work presents the results obtained in the analysis of rib bone samples from normal human individuals by applying instrumental neutron activation analysis. In these analyses, the elements Br, Cl, Fe, K, Mg, Na, Rb, Sr and Zn were found at the ppm level and the elements Ca and P at the level of percentage. The precision and the of the results were evaluated by using biological reference materials NIST SRM 1577a Bovine Liver, IAEA A-11 Milk powder, NIES CRM 9 Sargasso e NIES CRM 10A Rice Flour Unpolished. (author). 5 refs., 3 tabs

  15. Neutron activation analysis of calcium/phosphorus ratio in rib bone of healthy humans

    International Nuclear Information System (INIS)

    The Ca/P ratio was estimated in intact rib bone samples from healthy humans, 37 women and 45 men, aged from 15 to 55 years using instrumental neutron activation analysis. No statistically significant differences (p>0.05) age- or sex-related differences in the Ca/P ratio were observed. The mean value (M±SD) for the investigated parameter for the whole group studied, 2.33±0.34, was within a very wide range of published data and close to the median value

  16. The role of physical activity and diet on bone mineral indices in young men: a cross-sectional study

    OpenAIRE

    Liberato, Selma C; Bressan, Josefina; Hills, Andrew P.

    2013-01-01

    Background Osteoporotic fractures are a significant cause of morbidity and mortality, particularly in developed countries. Increasing peak bone mass in young people may be the most important primary prevention strategy to reduce the risk of osteoporosis. This study aimed to examine the relationship between dietary factors and physical activity on bone mineralization in young men. Methods Thirty-five healthy men aged 18–25 y had anthropometric measures, body composition, resting metabolic rate...

  17. Inhibition of bone resorption by the cathepsin K inhibitor odanacatib is fully reversible.

    Science.gov (United States)

    Zhuo, Y; Gauthier, J-Y; Black, W C; Percival, M D; Duong, L T

    2014-10-01

    The cathepsin K (CatK) inhibitor odanacatib (ODN) is currently being developed for the treatment of osteoporosis. In clinical trials, efficacy and resolution of effect of ODN treatment on bone turnover biomarkers and accrued bone mass have been demonstrated. Here, we examine the effects of continuing treatment and discontinuation of ODN versus alendronate (ALN) on osteoclast (OC) function. First, accessibility and reversible engagement of active CatK in intracellular vesicles and resorption lacunae of actively resorbing OCs were demonstrated by the selective and reversible CatK inhibitors, BODIPY-L-226 (IC50=39nM) and L-873,724 (IC50=0.5nM). Next, mature human OCs on bone slices were treated with vehicle, ODN, or ALN for 2days, followed by either continuing with the same treatment, or replacement of the inhibitors by vehicle for additional times as specified per experimental conditions. Maintaining OCs on ODN or ALN significantly reduced CTx-I release compared to vehicle controls. However, only the treatment of OCs with ODN resulted in the formation of small shallow discrete resorption pits, retention of intracellular vesicles enriched with CatK and other lysosomal enzymes, increase in 1-CTP release and number of TRAP(+) OCs. Upon discontinuation of ODN treatment, OCs rapidly resumed bone resorption activity, as demonstrated by a return of OC functional markers (CTx-I, 1-CTP), cell number and size, morphology and number of resorption pits, and vesicular secretion of CatK toward the respective vehicle levels. As expected, discontinuation of ALN did not reverse the treatment-related inhibition of OC activity in the time frame of the experiment. In summary, this study demonstrated rapid kinetics of inhibition and reversibility of the effects of ODN on OC bone resorption, that differentiated the cellular mechanism of CatK inhibition from that of the bisphosphate antiresorptive ALN. PMID:25038310

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

    Science.gov (United States)

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

    2016-08-01

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

  19. Structurally-diverse, PPARγ-activating environmental toxicants induce adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Environmental obesogens are a newly recognized category of endocrine disrupting chemicals that have been implicated in contributing to the rising rates of obesity in the United States. While obesity is typically regarded as an increase in visceral fat, adipocyte accumulation in the bone has been linked to increased fracture risk, lower bone density, and osteoporosis. Exposure to environmental toxicants that activate peroxisome proliferator activated receptor γ (PPARγ), a critical regulator of the balance of differentiation between adipogenesis and osteogenesis, may contribute to the increasing prevalence of osteoporosis. However, induction of adipogenesis and suppression of osteogenesis are separable activities of PPARγ, and ligands may selectively alter these activities. It currently is unknown whether suppression of osteogenesis is a common toxic endpoint of environmental PPARγ ligands. Using a primary mouse bone marrow culture model, we tested the hypothesis that environmental toxicants acting as PPARγ agonists divert the differentiation pathway of bone marrow-derived multipotent mesenchymal stromal cells towards adipogenesis and away from osteogenesis. The toxicants tested included the organotins tributyltin and triphenyltin, a ubiquitous phthalate metabolite (mono-(2-ethylhexyl) phthalate, MEHP), and two brominated flame retardants (tetrabromobisphenol-a, TBBPA, and mono-(2-ethylhexyl) tetrabromophthalate, METBP). All of the compounds activated PPARγ1 and 2. All compounds increased adipogenesis (lipid accumulation, Fabp4 expression) and suppressed osteogenesis (alkaline phosphatase activity, Osx expression) in mouse primary bone marrow cultures, but with different potencies and efficacies. Despite structural dissimilarities, there was a strong negative correlation between efficacies to induce adipogenesis and suppress osteogenesis, with the organotins being distinct in their exceptional ability to suppress osteogenesis. As human exposure to a mixture of

  20. In vivo quantification of bone-fluorine by delayed neutron activation analysis: a pilot study of hand-bone-fluorine levels in a Canadian population

    International Nuclear Information System (INIS)

    Humans can be exposed to fluorine (F) through their diet, occupation, environment and oral dental care products. Fluorine, at proper dosages, is believed to have positive effects by reducing the incidence of dental caries, but fluorine toxicity can occur when people are exposed to excessive quantities of fluorine. In this paper we present the results of a small pilot in vivo study on 33 participants living in Southwestern Ontario, Canada. The mean age of participants was 45 ± 18 years with a range of 20–87 years. The observed calcium normalized hand-bone-fluorine concentrations in this small pilot study ranged from 1.1 to 8.8 mg F/g Ca. Every person measured in this study had levels of fluorine in bone above the detection limit of the system. The average fluorine concentration in bone was found to be 3.5 ± 0.4 mg F/g Ca. No difference was observed in average concentration for men and women. In addition, a significant correlation (r2 = 0.55, p < 0.001) was observed between hand-bone-fluorine content and age. The amount of fluorine was found to increase at a rate of 0.084 ± 0.014 mg F/g Ca per year. There was no significant difference observed in this small group of subjects between the accumulation rates in men and women. To the best of our knowledge, this is the first time data from in vivo measurement of fluorine content in humans by neutron activation analysis have been presented. The data determined by this technique were found to be consistent with results from ex vivo studies from other countries. We suggest that the data demonstrate that this low risk non-invasive diagnostic technique will permit the routine assessment of bone-fluorine content with potential application in the study of clinical bone-related diseases. This small study demonstrated that people in Southern Ontario are exposed to fluoride in measureable quantities, and that fluoride can be seen to accumulate in bone with age. However, all volunteers were found to have levels below those

  1. Bone status of adult female butyrylcholinesterase gene-deficient mice.

    Science.gov (United States)

    Haupt, Malte; Kauschke, Vivien; Sender, Jonas; Kampschulte, Marian; Kovtun, Anna; Dürselen, Lutz; Heiss, Christian; Lips, Katrin Susanne

    2015-11-01

    Butyrylcholinesterase (BChE) degrades acetylcholine in addition to acetylcholinesterase (AChE) which is involved in embryonic development of limbs. Since BChE is expressed by osteoblast-like cells we asked whether it is functional in adult bone remodeling. We addressed this issue by analyzing BChE gene-deficient mice (BChE-KO). Bones were extracted from 16-week old female BChE-KO and corresponding wild type mice (WT). Femoral bones were used for biomechanical testing and μCT evaluation of cancellous and cortical bone. Also vertebrae Th12 and L1 were investigated with μCT while L3 was used for tartrate-resistant acidic phosphatase (TRAP) histomorphometry and Th10 for gene expression analysis by means of real-time RT-PCR. BChE-KO did not reveal significant differences in biomechanical bone strength and bone mineral density determined by μCT. Microarchitecture of cancellous and cortical bone showed an increase in μCT parameters like trabecular thickness, trabecular separation, and relative cortical bone area of femoral BChE-KO bone compared to WT. In vertebrae no changes of microstructure and mRNA expression were detected. However, osteoclast histomorphometry with TRAP stained sections demonstrated a significant increase in relative osteoclast number. In conclusion, in adult murine bone the role of BChE is limited to bone specific changes in microarchitecture and to an increase in relative number of bone resorbing osteoclasts whereas the main collagen resorbing enzyme Cathepsin-K (CtsK) was stably expressed. Besides, AChE might be able to compensate the lack of BChE. Thus, further analyses using bone tissue specific AChE BChE cre-lox double knockout mice would be helpful. PMID:26138460

  2. The Macrophage Inflammatory Proteins MIP1α (CCL3 and MIP2α (CXCL2 in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

    Directory of Open Access Journals (Sweden)

    Ulrike Dapunt

    2014-01-01

    Full Text Available Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3 and MIP2α (CXCL2 was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis.

  3. The mean active bone marrow dose to the adult population of the United States from diagnostic radiology

    International Nuclear Information System (INIS)

    Estimates, based on an empirical model and computer program, have been calculated and are presented on the mean active bone marrow dose to adults from diagnostic radiography, fluoroscopy, and dental radiography as practiced in the United States in 1970. The annual per capita mean active bone marrow dose in 1970 to adults from the above practices is estimated to be 103 mrad; 77 percent, 20 percent, and 3 percent from radiographic, fluoroscopic and dental examinations respectively. Examinations of the upper and lower abdomen contribute approximately 39 percent each to the total mean active bone marrow dose for adults; those of the pelvis 4 percent; the thorax 12 percent; and head and neck examinations (including dental) contribute about 6 percent. The per capita mean active bone marrow dose for various age groups is discussed. Contributions to the dose within a given age group from different examinations indicate that in the 15-34 year old age group Lumbar and Lumbosacral Spine examinations contribute most to the mean active bone marrow dose. Thereafter Upper G I Series and Barium Enemas are the highest contributors. Comparisons are made with results of the 1964 U.S. X-ray survey and similar surveys from other nations

  4. Physical Activity Level of Post-menopausal Women with Low Bone Mineral Density.

    Science.gov (United States)

    Dallanezi, Glauber; Freire, Beatriz Funayama Alvarenga; Nahás, Eliana Aguiar Petri; Nahás-Neto, Jorge; Corrente, José Eduardo; Mazeto, Gláucia Maria Ferreira da Silva

    2016-05-01

    Introduction Proper physical activity is related to the prevention and the treatment of osteoporosis. Purpose To assess the level of physical activity (PA) in post-menopausal women with low bone mineral density (BMD). Methods This cross-sectional clinical study included 123 post-menopausal women. The inclusion criteria were: age of ≥ 45 years with last menses at least 12 months prior to the initiation of the study, and bone density scan (BDS) values measured over the preceding 12 months. Women with severe osteoarthritis were excluded. Women were allocated into three groups, according to BMD measured by BDS [osteoporosis (OP; 54 women), osteopenia (35 women), and normal bone density (NBD; 35 women)], and compared for general, clinical, and anthropometric data, and for PA level. The latter was assessed using the International Physical Activity Questionnaire (IPAQ), in metabolic equivalent of task (MET) units. Participants were classified as sedentary, active or very active. Quantitative variables were compared using ANOVA followed by Tukey's test. Associations between qualitative variables were tested by Chi-square (χ2) or Fisher's exact test. In order to check for differences among groups and IPAQ domains, a generalized linear model with Gamma distribution was adjusted for values in METs. Results The OP group differed from the NBD group regarding age (61.8 ± 10.1 and 52.9 ± 5.4 years), percentage of participants with self-declared white ethnicity (43.9 and 28.0%), body mass index (BMI - 25.7 ± 5.4 and 30.9 ± 5.1 kg/m(2)), and time since menopause (15.5 ± 7.5 and 5.8 ± 4.5 years). Smoking rates were higher in the OP (55.6%) and NBD groups (33.3%) than in the osteopenia group (11.1%). Within the OP group, the rate of subjects with sedentary lifestyles was higher (42.6%), and time spent sitting was greater (344.3 ± 204.8 METs) than in the groups with osteopenia (20.0% and 300.9 ± 230.6 METs) and NBD (17.7% and 303

  5. Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To determine whether interleukin-1α and 1β gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1β and rheumatoid arthritis (RA) motif gene. Methods IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1α-889 and IL-1β+3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1β2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data.Results There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and the controls. The β2/2 genotype of IL-1β was more common in female RA patients compared with controls (P=0.001). A lower carriage rate of IL-1β2 occurred in male RA patients (P=0.001). A higher carriage rate of IL-1α2 is associated with a higher ESR (P=0.008), HAQ score (P=0.03), and vit-D3 (P<0.001), but conversely a lower SJC (p=0.002), a lower RF (P=0.002) and a lower BMD at the lumbar spine (P=0.001). A higher frequency of IL-1α1 is associated with a lower CRP value (P=0.009). An increased IL-1β2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P<0.001), ESR (P<0.001) and pain score (P=0.001) and a higher BMD at the lumbar spine (P=0.007), lower vit-D3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time did not contribute to disease activity

  6. Ethanol Extracts of Fresh Davallia formosana (WL1101 Inhibit Osteoclast Differentiation by Suppressing RANKL-Induced Nuclear Factor-κB Activation

    Directory of Open Access Journals (Sweden)

    Tzu-Hung Lin

    2013-01-01

    Full Text Available The rhizome of Davallia formosana is commonly used to treat bone disease including bone fracture, arthritis, and osteoporosis in Chinese herbal medicine. Here, we report the effects of WL1101, the ethanol extracts of fresh rhizomes of Davallia formosana on ovariectomy-induced osteoporosis. In addition, excess activated bone-resorbing osteoclasts play crucial roles in inflammation-induced bone loss diseases, including rheumatoid arthritis and osteoporosis. In this study, we examined the effects of WL1101 on receptor activator of nuclear factor-κB ligand (RANKL-induced osteoclastogenesis. Treatment with WL1101 significantly inhibited RANKL-stimulated osteoclastogenesis. Two isolated active compounds, ((−-epicatechin or WL14 (4-hydroxy-3-aminobenzoic acid could also inhibit RANKL-induced osteoclastogenesis. WL1101 suppressed the RANKL-induced nuclear factor-κB (NF-κB activation and nuclear translocation, which is the key process during osteoclastogenesis, by inhibiting the activation of IκB kinase (IKK and IκBα. In animal model, oral administration of WL1101 (50 or 200 mg/kg/day effectively decreased the excess bone resorption and significantly antagonized the trabecular bone loss in ovariectomized rats. Our results demonstrate that the ethanol extracts of fresh rhizomes of Davallia formosana inhibit osteoclast differentiation via the inhibition of NF-κB activation and effectively ameliorate ovariectomy-induced osteoporosis. WL1101 may thus have therapeutic potential for the treatment of diseases associated with excessive osteoclastic activity.

  7. The characteristics of physical activity and gait in patients receiving radiotherapy in cancer induced bone pain

    International Nuclear Information System (INIS)

    Background and purpose: An objective measure of pain relief may add important information to patients’ self assessment, particularly after a treatment. The study aims were to determine whether measures of physical activity and/or gait can be used in characterizing cancer-induced bone pain (CIBP) and whether these biomarkers are sensitive to treatment response, in patients receiving radiotherapy (XRT) for CIBP. Materials and methods: Patients were assessed before (baseline) and 6–8 weeks after XRT (follow up). The following assessments were done: Brief Pain Inventory (BPI), activPAL™ activity meter, and GAITRite® electronic walkway (measure of gait). Wilcoxon, Mann–Whitney and Pearson statistical analyses were done. Results: Sixty patients were assessed at baseline; median worst pain was 7 and walking interference was 5. At follow up 42 patients were assessed. BPI worst pain, average pain, walking interference and total functional interference all improved (p < 0.001). An improvement in functional interference correlated with aspects of physical activity (daily hours standing r = 0.469, p = 0.002) and gait (cadence r = 0.341, p = 0.03). The activPAL and GAITRite parameters did not change following XRT (p > 0.05). In responder analyses there were no differences in activPAL and GAITRite parameters (p > 0.05). Conclusion: Assessment of physical activity and gait allow a characterization of the functional aspects of CIBP, but not in the evaluation of XRT

  8. Characterization of the molecular mechanism of the bone-anabolic activity of carfilzomib in multiple myeloma.

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    Bo Hu

    Full Text Available Carfilzomib, the next generation of proteasome inhibitor, may increase osteoblast-related markers in patients with multiple myeloma, but the molecular mechanism of its effect on mesenchymal stem cell differentiation to osteoblasts remains unknown. Herein, we demonstrated that carfilzomib significantly promoted mesenchymal stem cell differentiation into osteoblasts. In osteoprogenitor cells and primary mesenchymal stem cells from patients with myeloma, carfilzomib induced increases in alkaline phosphatase activity, matrix mineralization, and calcium deposition via Wnt-independent activation of β-catenin/TCF signaling. Using affinity pull-down assays with immunoblotting analysis and immunofluorescence, we found that carfilzomib induced stabilization of both free and active forms of β-catenin in a time- and dose-dependent manner that was not associated with β-catenin transcriptional regulation. Nuclear translocation of β-catenin protein was associated with TCF transcriptional activity that was independent of the effects of GSK3β-activation and of signaling induced by 19 Wnt ligands, 10 Frizzled receptors, and LRP5/6 co-receptors. Blocking activation of β-catenin/TCF signaling by dominant negative TCF1 or TCF4 attenuated carfilzomib-induced matrix mineralization. Thus, carfilzomib induced osteoblast differentiation via Wnt-independent activation of the β-catenin/TCF pathway. These results provide a novel molecular mechanism critical to understanding the anabolic role of carfilzomib on myeloma-induced bone disease.

  9. Melt-electrospun polycaprolactone strontium-substituted bioactive glass scaffolds for bone regeneration.

    Science.gov (United States)

    Ren, Jiongyu; Blackwood, Keith A; Doustgani, Amir; Poh, Patrina P; Steck, Roland; Stevens, Molly M; Woodruff, Maria A

    2014-09-01

    Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue engineering owing to good structural properties and processability. Strontium-substituted bioactive glass (SrBG) has the ability to promote osteogenesis and may be incorporated into scaffolds intended for bone repair. Here, we describe for the first time, the development of a PCL-SrBG composite scaffold incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the technique of melt electrospinning. We show that we are able to reproducibly manufacture composite scaffolds with an interconnected porous structure and, furthermore, these scaffolds were demonstrated to be noncytotoxic in vitro. Ions present in the SrBG component were shown to dissolve into cell culture media and promoted precipitation of a calcium phosphate layer on the scaffold surface which in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3-E1 cells compared to PLC-only scaffolds. These results suggest that melt-electrospun PCL-SrBG composite scaffolds show potential to become effective bone graft substitutes. PMID:24133006

  10. Effect of hyperhydration on bone mineralization in physically healthy subjects after prolonged restriction of motor activity

    Science.gov (United States)

    Zorbas, Yan G.; Federenko, Youri F.; Naexu, Konstantin A.

    The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on bone mineralization in physically healthy male volunteers after exposure to hypokinesia (decreased number of steps taken/day) over a period of 364 days. The studies were performed after exposure to 364 days of hypokinesia (HK) on 18 physically healthy male volunteers who had an average VO2max of 65 ml/kg/min and were aged between 19 and 24 years. For the simulation of the hypokinetic effect the volunteers were kept under an average of 1000 steps/day. The subjects were divided into three equal groups of 6: 6 underwent a normal ambulatory life (control group), 6 were placed under HK (hypokinetic group) and the remaining 6 were subjected to HK and consumed a daily FSS (water 26 ml/kg body wt and NaCl 0.10 mg/kg body wt) (hyperhydrated group). The density of the ulnar, radius, tibia, fibular, lumbar vertebrae and calcenous was measured. Calcium and phosphorus changes, plasma volume, blood pressure and body weight were determined. Calcium content in the examined skeletal bones decreased more in the hypokinetic subjects than in the hyperhydrated subjects. Urinary calcium and phosphorus losses were more pronounced in hypokinetic than hyperhydrated subjects. Plasma volume and body weight increased in hyperhydrated subjects, while it decreased in hypokinetic subjects. It was concluded that a daily intake of FSS may be used to neutralize bone demineralization in physically healthy subjects during prolonged restriction of motor activity.

  11. The Multifaceted Osteoclast; Far and Beyond Bone Resorption.

    Science.gov (United States)

    Drissi, Hicham; Sanjay, Archana

    2016-08-01

    The accepted function of the bone resorbing cell, osteoclast, has been linked to bone remodeling and pathological osteolysis. Emerging evidence points to novel functions of osteoclasts in controlling bone formation and angiogenesis. Thus, while the concept of a "clastokine" with the potential to regulate osteogenesis during remodeling did not come as a surprise, new evidence provided unique insight into the mechanisms underlying osteoclastic control of bone formation. The question still remains as to whether osteoclast precursors or a unique trap positive mononuclear cell, can govern any aspect of bone formation. The novel paradigm eloquently proposed by leaders in the field brings together the concept of clastokines and osteoclast precursor-mediated bone formation, potentially though enhanced angiogenesis. These fascinating advances in osteoclast biology have motivated this short review, in which we discuss these new roles of osteoclasts. J. Cell. Biochem. 117: 1753-1756, 2016. © 2016 Wiley Periodicals, Inc. PMID:27019318

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

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    Takashi Watanabe

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

  13. Osteogenetic activity in composite grafts of demineralized compact bone and marrow

    International Nuclear Information System (INIS)

    The effects of a composite graft of autologous marrow and demineralized autologous compact bone on the healing of a surgically created bone defect were observed in adult rabbits. A segment of the radius was bilaterally resected, demineralized, and replaced. On one side the bone graft was supplemented with autologous marrow. The new bone formation was measured 14 and 28 days after operation by roentgenography, including planimetry with scintigraphy and autoradiography using /sup 99m/Tc-labelled MDP. The composite graft, i.e., demineralized compact bone and marrow, had a significantly higher (p less than 0.01) bone formation rate 14 days after operation compared with the graft with demineralized compact bone in the opposite radius. At 28 days, however, there were no differences between the sides. Viable autologous marrow cells and demineralized autologous compact bone graft accelerate the rate of osteogenesis, but only at the beginning of the healing process

  14. Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Halberg, P; Kollerup, G;

    1998-01-01

    The bone metabolism in patients with systemic lupus erythematosus (SLE) has previously been examined, but the results are conflicting. In the present study the bone mineral density (BMD) of the axial and the appendicular skeleton was examined by means of dual energy x-ray absorptiometry. The bone...

  15. Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

    Science.gov (United States)

    A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma ch...

  16. Postmenopausal women with osteoarthritis and osteoporosis show different ultrastructural characteristics of trabecular bone of the femoral head

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    Jiang Lei-Sheng

    2009-04-01

    Full Text Available Abstract Background Osteoporosis (OP and osteoarthritis (OA are public health diseases affecting the quality of life of the elderly, and bring about a heavy burden to the society and family of patients. It has been debated whether or not there is an inverse relationship between these two disorders. Methods To compare the exact difference in bone tissue structure between osteoporosis and osteoarthritis, we observed the ultrastructure of trabecular bone from the femoral heads using scanning electron microscopy (SEM and transmission electron microscopy (TEM. A total of 15 femoral head specimens from postmenopausal women were collected during the procedures of total or hemi hip replacement (OP, n = 8; OA, n = 7. The morphologic structure of the trabecular bone, collagen fibers, resorption lacuna and osteoblasts were observed. Results Under SEM, osteoporotic trabeculae appeared to be thinning, tapering, breaking and perforating. A number of resorption lacunae of various shapes were seen on the surface of the trabeculum. The collagen fibers of lacuna were resorbed. On occasion, naked granular bone crystals could be found. In the OA group, the trabecular bone looked thick with integrated structure. Reticular and granular new bone could be found. The trabeculum was covered by well-arranged collagen fibers around the resorption lacuna. In the OP group, under TEM, marginal collagen fibers were observed to be aligned loosely with enlarged spaces. A few inactive osteoblasts and no inflammatory cells were seen. In the OA group, the collagen fibers inside the trabeculum were arranged in a dense manner with many active osteoblasts and inflammatory cells infiltrating the matrix. Conclusion We found significant differences in the trabecular bone, collagen fibers, lacunae and osteoblasts between postmenopausal women with OP and OA. These findings support the hypothesis that there is an inverse relationship between OP and OA.

  17. Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells

    Science.gov (United States)

    McAllister, T. N.; Du, T.; Frangos, J. A.

    2000-01-01

    Bone is a porous tissue that is continuously perfused by interstitial fluid. Fluid flow, driven by both vascular pressure and mechanical loading, may generate significant shear stresses through the canaliculi as well as along the bone lining at the endosteal surface. Both osteoblasts and osteocytes produce signaling factors such as prostaglandins and nitric in response to fluid shear stress (FSS); however, these humoral agents appear to have more profound affects on osteoclast activity at the endosteal surface. We hypothesized that osteoclasts and preosteoclasts may also be mechanosensitive and that osteoclast-mediated autocrine signaling may be important in bone remodeling. In this study, we investigated the effect of FSS on nitric oxide (NO), prostaglandin E(2) (PGE(2)), and prostacyclin (PGI(2)) release by neonatal rat bone marrow-derived preosteoclast-like cells. These cells were tartrate-resistant acid phosphatase (TRAP) positive, weakly nonspecific esterase (NSE) positive, and capable of fusing into calcitonin-responsive, bone-resorbing, multinucleated cells. Bone marrow-derived preosteoclast-like cells exposed for 6 h to a well-defined FSS of 16 dynes/cm(2) produced NO at a rate of 7.5 nmol/mg protein/h, which was 10-fold that of static controls. This response was completely abolished by 100 microM N(G)-amino-L-arginine (L-NAA). Flow also stimulated PGE(2) production (3.9 microg/mg protein/h) and PGI(2) production (220 pg/mg protein/h). L-NAA attenuated flow-induced PGE(2) production by 30%, suggesting that NO may partially modulate PGE(2) production. This is the first report demonstrating that marrow derived cells are sensitive to FSS and that autocrine signaling in these cells may play an important role in load-induced remodeling and signal transduction in bone. Copyright 2000 Academic Press.

  18. Lack of telomerase activity in rabbit bone marrow stromal cells during differentiation along neural pathway

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhen-zhou; XU Ru-xiang; JIANG Xiao-dan; TENG Xiao-hua; LI Gui-tao; ZHOU Yü-xi

    2006-01-01

    Objective: To investigate telomerase activity in rabbit bone marrow stromal cells (BMSCs) during their committed differentiation in vitro along neural pathway and the effect of glial cell line-derived neurotrophic factor (GDNF) on the expression of telomerase.Methods: BMSCs were acquired from rabbit marrow and divided into control group, GDNF (10 ng/ml) group.No. ZL02134314. 4) supplemented with 10% fetal bovine serum (FBS) was used to induce BMSCs differentiation along neural pathway. Fluorescent immunocytochemistry was employed to identify the expressions of Nestin, neuronspecific endase (NSE), and gial fibrillary acidic protein (GFAP). The growth curves of the cells and the status of cell cycles were analyzed, respectively. During the differentiation, telomerase activitys were detected using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA).Results: BMSCs were successfully induced to differentiate along neural pathway and expressed specific markers of fetal neural epithelium, mature neuron and glial cells. Telomerase activities were undetectable in BMSCs during differentiation along neural pathway. Similar changes of cell growth curves, cell cycle status and telomerase expression were observed in the two groups.Conclusions: Rabbit BMSCs do not display telomerase activity during differentiation along neural pathway. GDNF shows little impact on proliferation and telomerase activity of BMSCs.

  19. Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of inflammatory activators and hypoxia.

    Science.gov (United States)

    Maceckova, Michaela; Martiskova, Hana; Koudelka, Adolf; Kubala, Lukas; Lojek, Antonin; Pekarova, Michaela

    2015-11-01

    Caveolins are specific proteins involved in regulation of signal transduction to intracellular space. Still, their contribution to immune functions has not been completely clarified. Thus, we decided to characterize the expression of caveolins in bone marrow-derived macrophages (BMDMs) under resting and inflammatory conditions. The effect of classical activators (lipopolysaccharide, LPS; interferon-gamma, IFN-γ) was further potentiated with hypoxic (5% O2) conditions. The activation of p44/42-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and expression of caveolin-1, -2, and -3, hypoxia inducible factor-1 alpha (HIF-1α), as well as inducible nitric oxide synthase (iNOS) was monitored using the Western blot technique. The production of nitric oxide (NO) and tumor necrosis factor-alpha (TNFα) was analyzed by Griess method or ELISA, respectively. BMDMs were also transfected with siRNA against caveolin-2. Importantly, our study showed for the first time that BMDMs expressed only caveolin-2, and its level decreased after activation of macrophages with LPS, IFN-γ, and/or hypoxia. The expression of caveolin-2 negatively correlates with the iNOS and HIF-1α protein levels, as well as with the LPS/IFN-γ- and hypoxia-induced activation of ERK1/2. We concluded that caveolin-2 is most probably involved in regulation of pro-inflammatory responses of BMDMs, triggered via activation of ERK1/2. PMID:26215374

  20. Wnt5a/Ror2 mediates temporomandibular joint subchondral bone remodeling.

    Science.gov (United States)

    Yang, T; Zhang, J; Cao, Y; Zhang, M; Jing, L; Jiao, K; Yu, S; Chang, W; Chen, D; Wang, M

    2015-06-01

    Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2 signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role in modulating osteoblast and osteoclast formation. We showed previously that experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in regulating osteoclast precursor migration and differentiation in this process. The data confirmed the decreased bone mass, increased tartrate-resistant acid phosphatase (TRAP)-positive cell number, and enhanced osteoclast activity in TMJ subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated rats was also enhanced, displaying as upregulated expressions of osteoblast markers and increased proliferation, migration, and differentiation capabilities of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and Ror2. Ex vivo data showed that their capacities of inducing migration and differentiation of osteoclast precursors were enhanced, and these enhanced capabilities were restrained after blocking their Ror2 signaling using small interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by siRNA or blocking the downstream signalings with specific inhibitors also demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a-dependent migration (including SP600125 and cyclosporine A) and differentiation (cyclosporine A only) of osteoclast precursors. These findings support the idea that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs to increase Cxcl12 and Rankl

  1. SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) and 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer

  2. Calcite as a bone substitute. Comparison with hydroxyapatite and tricalcium phosphate with regard to the osteoblastic activity

    Energy Technology Data Exchange (ETDEWEB)

    Monchau, F., E-mail: Francine.monchau@univ-artois.fr [Laboratoire Genie Civil et geo-Environnement (EA 4515, Universite Lille Nord de France), Equipe Biomateriaux Artois (Universite d' Artois), IUT/GMP, 1230, rue de l' Universite, BP 819, 62408 Bethune cedex (France); Hivart, Ph.; Genestie, B. [Laboratoire Genie Civil et geo-Environnement (EA 4515, Universite Lille Nord de France), Equipe Biomateriaux Artois (Universite d' Artois), IUT/GMP, 1230, rue de l' Universite, BP 819, 62408 Bethune cedex (France); Chai, F. [Laboratoire Medicaments et Biomateriaux a Liberation Controlee (INSERM U 1008, Universite Lille Nord de France), Groupe de Recherche sur les Biomateriaux (Universite Lille-2), Faculte de Medecine, 1, place de Verdun, 59045 Lille cedex (France); and others

    2013-01-01

    Close to the bone mineral phase, the calcic bioceramics, such as hydroxyapatite (HA) and {beta}-tricalcium phosphate ({beta}-TCP), are commonly used as substitutes or filling materials in bone surgery. Besides, calcium carbonate (CaCO{sub 3}) is also used for their excellent biocompatibility and bioactivity. However, the problem with the animal-origin aragonite demands the new technique to synthesize pure calcite capable of forming 3D bone implant. This study aims to manufacture and evaluate a highly-pure synthetic crystalline calcite with good cytocompatibility regarding to the osteoblasts, comparing to that of HA and {beta}-TCP. After the manufacture of macroporous bioceramic scaffolds with the identical internal architecture, their cytocompatibility is studied through MC3T3-E1 osteoblasts with the tests of cell viability, proliferation, vitality, etc. The results confirmed that the studied process is able to form a macroporous material with a controlled internal architecture, and this synthesized calcite is non-cytotoxic and facilitate the cell proliferation. Indeed requiring further improvement, the studied calcite is definitely an interesting alternative not only to coralline aragonite but also to calcium phosphate ceramics, particularly in bone sites with the large bone remodelling. Highlights: Black-Right-Pointing-Pointer Macroporous calcite manufacturing with controlled architecture as bone substitute Black-Right-Pointing-Pointer Cytotoxicity: adaptation of the colony-forming method with the target cells: MC3T3-E1 osteoblasts Black-Right-Pointing-Pointer Study of osteoblast proliferation and activity on calcite, HA and TCP.

  3. Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating JNK/c-Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in Mice.

    Science.gov (United States)

    Park, Sun-Hyang; Kim, Ju-Young; Cheon, Yoon-Hee; Baek, Jong Min; Ahn, Sung-Jun; Yoon, Kwon-Ha; Lee, Myeung Su; Oh, Jaemin

    2016-04-01

    Protocatechuic acid (PCA) plays a critical role in nutritional metabolism; it is a major metabolite of anthocyanins, which are flavonoids with a range of health benefits. PCA has a variety of biological activities including anti-oxidant, antiinflammatory, anti-apoptosis, and anti-microbial activities. However, the pharmacological effect of PCA, especially on osteoclastogenesis, remains unknown. We examined the effect of PCA on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption. PCA dose-dependently inhibited RANKL-induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and suppressed the bone-resorbing activity of mature osteoclasts. At the molecular level, PCA suppressed RANKL-induced phosphorylation of JNK among MAPKs only, without significantly affecting the early signaling pathway. PCA also suppressed RANKL-stimulated expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) at the mRNA and protein levels, without altering c-Fos mRNA expression. Additionally, PCA down-regulated the expression of downstream osteoclastogenesis-related genes including β3-integrin, DC-STAMP, OC-STAMP, Atp6v0d2, CTR, and CtsK. Mice treated with PCA efficiently recovered from lipopolysaccharide-induced bone loss in vivo. Thus, PCA inhibits RANKL-induced osteoclast differentiation and function by suppressing JNK signaling, c-Fos stability, and expression of osteoclastic marker genes. These results suggest that PCA could be useful in treatment of inflammatory bone disorders. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26792397

  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. Cold water cleaning of brain proteins, biofilm and bone - harnessing an ultrasonically activated stream.

    Science.gov (United States)

    Birkin, P R; Offin, D G; Vian, C J B; Howlin, R P; Dawson, J I; Secker, T J; Hervé, R C; Stoodley, P; Oreffo, R O C; Keevil, C W; Leighton, T G

    2015-08-28

    In the absence of sufficient cleaning of medical instruments, contamination and infection can result in serious consequences for the health sector and remains a significant unmet challenge. In this paper we describe a novel cleaning system reliant on cavitation action created in a free flowing fluid stream where ultrasonic transmission to a surface, through the stream, is achieved using careful design and control of the device architecture, sound field and the materials employed. Cleaning was achieved with purified water at room temperature, moderate fluid flow rates and without the need for chemical additives or the high power consumption associated with conventional strategies. This study illustrates the potential in harnessing an ultrasonically activated stream to remove biological contamination including brain tissue from surgical stainless steel substrates, S. epidermidis biofilms from glass, and fat/soft tissue matter from bone structures with considerable basic and clinical applications. PMID:26200694

  6. Bone tumor

    Science.gov (United States)

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

  7. Bone Grafts

    Science.gov (United States)

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

  8. Structural changes and biological responsiveness of an injectable and mouldable monetite bone graft generated by a facile synthetic method

    OpenAIRE

    Cama, G.; Gharibi, B.; Knowles, J. C.; Romeed, S.; DiSilvio, L.; Deb, S

    2014-01-01

    Brushite (dicalcium phosphate dihydrate) and monetite (dicalcium phosphate anhydrous) are of considerable interest in bone augmentation owing to their metastable nature in physiological fluids. The anhydrous form of brushite, namely monetite, has a finer microstructure with higher surface area, strength and bioresorbability, which does not transform to the poorly resorbable hydroxyapatite, thus making it a viable alternative for use as a scaffold for engineering of bone tissue. We recently re...

  9. The Masticatory Contractile Load Induced Expression and Activation of Akt1/PKBα in Muscle Fibers at the Myotendinous Junction within Muscle-Tendon-Bone Unit

    OpenAIRE

    Yüksel Korkmaz; Franz J. Klinz; Mehrnoush Moghbeli; Klaus Addicks; Wolfgang H.-M. Raab; Wilhelm Bloch

    2010-01-01

    The cell specific detection of enzyme activation in response to the physiological contractile load within muscle-tendon-bone unit is essential for understanding of the mechanical forces transmission from muscle cells via tendon to the bone. The hypothesis that the physiological mechanical loading regulates activation of Akt1/PKBα at Thr308 and at Ser473 in muscle fibers within muscle-tendon-bone unit was tested using quantitative immunohistochemistry, confocal double fluorescence analy...

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

    OpenAIRE

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

    1984-01-01

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

  11. Use of the plasma CTX for assessing the bone activity of the mandible among osteopenic and osteoporotic patients

    Directory of Open Access Journals (Sweden)

    Glacio Avolio

    2010-06-01

    Full Text Available The aim of this study was to determine whether the plasma CTX bone remodeling marker is useful for indicating the bone metabolic activity level of the mandible. Thirty-six patients were selected; all were postmenopausal and aged 50 years or over. In accordance with the WHO criteria for osteoporosis, a control group was set up (n = 10 in which the T-score was greater than -1 and a diseased group with T-score less than -1. Using MDP-99mTc samples, the radioisotope uptake in the femoral neck (R2 and mandibular body (R1 was analyzed. A third examination was performed using the plasma CTX biochemical bone-modeling marker. The inferential results for the diseased group showed that Ln(R1 presented a statistically significant linear relationship with Ln(CTx (p = 0.067 and with the T-score (p = 0.018. The plasma CTX bone remodeling marker is useful for monitoring the bone metabolic activity of the mandible.

  12. The use of a resorbable augmentation device to secure plating of osteoporotic bones : An in vitro study

    OpenAIRE

    P Mainil-Varlet; Cordey, J.; Landolt, M.; Gogolewski, S

    1997-01-01

    Osteotomies in porotic human cadaveric humeri were fixed with metallic plates and screws in 3 experimental groups. In group I, osteotomies of the 3 arbitrarily chosen humeri were plated without reinforcement. The osteotomies of the contralateral 3 humeri were plated after reinforcement with a poly(L-lactide) augmentation device. In group II, osteotomies on one side were plated without reinforcement, but those of the contralateral humeri were plated after reinforcement ...

  13. Fibroblast activation protein (FAP is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation.

    Directory of Open Access Journals (Sweden)

    Kuei-Min Chung

    Full Text Available BACKGROUND: The ability of human bone marrow mesenchymal stem cells (BM-MSCs to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. PRINCIPAL FINDINGS: We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β and transforming growth factor-beta (TGF-β upregulated FAP expression, which coincided with better BM-MSC migration. CONCLUSIONS: Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration.

  14. Antibiotic-decorated titanium with enhanced antibacterial activity through adhesive polydopamine for dental/bone implant.

    Science.gov (United States)

    He, Shu; Zhou, Ping; Wang, Linxin; Xiong, Xiaoling; Zhang, Yifei; Deng, Yi; Wei, Shicheng

    2014-06-01

    Implant-associated infections, which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, practical approaches to prevent implant-associated infections are in great demand. Inspired by adhesive proteins in mussels, here we have developed a novel antibiotic-decorated titanium (Ti) material with enhanced antibacterial activity. In this study, Ti substrate was coated by one-step pH-induced polymerization of dopamine followed by immobilization of the antibiotic cefotaxime sodium (CS) onto the polydopamine-coated Ti through catechol chemistry. Contact angle measurement and X-ray photoelectron spectroscopy confirmed the presence of CS grafted on the Ti surface. Our results demonstrated that the antibiotic-grafted Ti substrate showed good biocompatibility and well-behaved haemocompatibility. In addition, the antibiotic-grafted Ti could effectively prevent adhesion and proliferation of Escherichia coli (Gram-negative) and Streptococcus mutans (Gram-positive). Moreover, the inhibition of biofilm formation on the antibiotic-decorated Ti indicated that the grafted CS could maintain its long-term antibacterial activity. This modified Ti substrate with enhanced antibacterial activity holds great potential as implant material for applications in dental and bone graft substitutes. PMID:24647910

  15. Bone Mineral Density Changes after Physical Training and Calcium Intake in Students with Attention Deficit and Hyper Activity Disorders

    Science.gov (United States)

    Arab ameri, Elahe; Dehkhoda, Mohammad Reza; Hemayattalab, Rasool

    2012-01-01

    In this study we investigate the effects of weight bearing exercise and calcium intake on bone mineral density (BMD) of students with attention deficit and hyper activity (ADHD) disorder. For this reason 54 male students with ADHD (age 8-12 years old) were assigned to four groups with no differences in age, BMD, calcium intake, and physical…

  16. Bone density at the os calcis: reference values, reproducibility, and effects of fracture history and physical activity

    OpenAIRE

    Chinn, D.; Fordham, J.; Kibirige, M; Crabtree, N; Venables, J; Bates, J.; Pitcher, O

    2005-01-01

    Aims: To establish reference values for bone mineral density (BMD) measured at the os calcis (OC) in healthy UK Caucasian children. Secondary objectives were to assess the reproducibility of the measurement and the effects of fracture history and habitual physical activity.

  17. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    International Nuclear Information System (INIS)

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease. (author)

  18. Activation and track analysis of the bone remains found in the territory of Uzbekistan

    International Nuclear Information System (INIS)

    Full text : As a rule bones of animals and persons, are plentiful enough in archeology monuments and are frequently also the most numerous materials. Therefore the research of components and microelements in bones can give the valuable information about age and lifestyle of prehistoric relicts on Earth. To ancient bone remains bear and archantrope concernfrom ancient settlement of Selungur located in the territory of Southern Fergana and was found out by Institute of Archaeology in Uzbekistan in 1980. Whereas in the scientific literature there is very poor information about element composition variation in bones during ground bedding

  19. Multi-element analysis of bone from the osteogenesis imperfecta model (OIM) mouse using thermal and fast neutron activation analysis

    International Nuclear Information System (INIS)

    Osteogenesis imperfecta (OI) is a heritable osteoporotic bone disease, due to defects in either type I procollagen genes (COL1A1 or COL1A2), resulting in abnormal and/or reduced levels of type I procollagen and alterations in bone mineralization. Our long term objectives are to evaluate the impact of proα1(I) and proα2(I) collagen mutations and the role of the genetic background on bone mineralization. Tibias from wildtype, heterozygous (oim/+), and homozygous (oim/oim) animals were subjected to instrumental neutron activation analysis (INAA) to measure F, P, Na, Mg, Cl, Ca, K, and Zn using the University of Missouri Research Reactor (MURR) pneumatic-tube irradiation facility. (author)

  20. Variation in the bone calcium concentration as a function of age and sex, studied by local neutron activation in vivo

    International Nuclear Information System (INIS)

    An original method of local activation on the hand, using isotopic neutron sources, was used to determine bone Ca and P simultaneously. The calcium concentration variation with age and sex was studied on 120 normal subjects men and women aged between 20 and 80, divided into 10 year age groups. These standards were chosen amongst subjects free from complaints liable to affect bone mineralisation and with more or less normal blood calcium and phosphorus contents. The results are as follows: between 20 and 50 the relative standard derivation observed within a 10 year age group averages 8% in men and 9% in women, after 50 this physiological scattering is much greater in both sexes, after 60 the bone calcium concentration decreases quickly in women at an average rate of 1.15% a year

  1. Differential influence of physical activity on lumbar spine and femoral neck bone mineral density in the elderly population.

    Science.gov (United States)

    Vuillemin, A; Guillemin, F; Jouanny, P; Denis, G; Jeandel, C

    2001-06-01

    This study investigates the relationship between lifetime physical activity and bone mineral density (BMD) at various sites in 129 healthy men and women aged 72.1 +/- 6.5 years. BMD was measured by dual energy x-ray absorptiometry, and physical activity was assessed by using the QUANTAP system (Quantification de l'Activité Physique), a standardized and structured computer-assisted interview tool designed to assess lifetime physical activity. Linear regression models controlling for age, gender, height, body mass, lean mass, and smoking habits were performed. Higher levels of sporting activity during youth were associated with greater lumbar spine BMD ( p construction and bone aging taking place at the time. PMID:11382786

  2. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    Directory of Open Access Journals (Sweden)

    Anne-Priscille Trouvin

    2010-11-01

    Full Text Available Anne-Priscille Trouvin, Vincent GoëbDepartment of Rheumatology, Rouen University Hospital, Rouen, FranceAbstract: Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG and receptor activator for nuclear factor-κB (RANK ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, the RANK/RANKL/OPG pathway is described. The multiple interactions of various factors (hormones, cytokines, growth factors, and vitamins with the OPG/RANK/RANKL pathway are also commented on. Finally, the effects of denosumab, a human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts, and of strontium ranelate are also described. Indeed, these two new drugs afford appreciable assistance in daily care practice, helping to prevent bone loss in patients with osteoporosis.Keywords: osteoprotegerin, OPG, RANK, RANKL, denosumab, strontium ranelate, osteoporosis

  3. Bone mineralization pathways during the rapid growth of embryonic chicken long bones.

    Science.gov (United States)

    Kerschnitzki, Michael; Akiva, Anat; Ben Shoham, Adi; Asscher, Yotam; Wagermaier, Wolfgang; Fratzl, Peter; Addadi, Lia; Weiner, Steve

    2016-07-01

    The uptake and transport of ions from the environment to the site of bone formation is only partially understood and, for the most part, based on disparate observations in different animals. Here we study different aspects of the biomineralization pathways in one system, the rapidly forming long bones of the chicken embryo. We mainly used cryo-fixation and cryo-electron imaging to preserve the often unstable mineral phases in the tissues. We show the presence of surprisingly large amounts of mineral particles located inside membrane-delineated vesicles in the bone forming tissue between the blood vessels and the forming bone surface. Some of these particles are also located inside mitochondrial networks. The surfaces of the forming bones in the extracellular space contain abundant aggregates of amorphous calcium phosphate particles, but these are not enveloped by vesicle membranes. In the bone resorbing region, osteoclasts also contain many particles in both mitochondrial networks and within vesicles. Some of these particles are present also between cells. These observations, together with the previously reported observation that CaP mineral particles inside membranes are present in blood vessels, leads us to the conclusion that important components of the bone mineralization pathways in rapidly forming chicken bone are dense phase mineral particles bound within membranes. It remains to be determined whether these mineral particles are transported to the site of bone formation in the solid state, fluid state or dissolve and re-precipitate. PMID:27108185

  4. Gelatin-Modified Bone Substitute with Bioactive Molecules Enhance Cellular Interactions and Bone Regeneration.

    Science.gov (United States)

    Teotia, Arun Kumar; Gupta, Ankur; Raina, Deepak Bushan; Lidgren, Lars; Kumar, Ashok

    2016-05-01

    In this work, we have synthesized injectable bone cement incorporated with gelatin to enhance cellular interaction. Human osteosarcoma Saos-2 cells derived bone morphogenetic proteins (BMP's) and a bisphosphonate (zoledronic acid (0.2 mM)) were also incorporated to cement. In vitro studies conducted using Saos-2 demonstrated enhanced cell proliferation on gelatin (0.2%w/v) cement. The differentiation of C2C12 mouse myoblast cells into bone forming cells showed 6-fold increase in ALP levels on gelatin cement. Polymerase chain reaction (PCR) for bone biomarkers showed osteoinductive potential of gelatin cement. We investigated efficacy for local delivery of these bioactive molecules in enhancing bone substitution qualities of bone cements by implanting in 3.5 mm critical size defect in tibial metaphysis of wistar rats. The rats were sacrificed after 12 weeks and 16 weeks post implantation. X-ray, micro-CT, histology, and histomorphometry analysis were performed to check bone healing. The cement materials slowly resorbed from the defect site leaving HAP creating porous matrix providing surface for bone formation. The materials showed high biocompatibility and initial bridging was observed in all the animals but maximum bone formation was observed in animals implanted with cement incorporated with zoledronic acid followed by cement with BMP's compared to other groups. PMID:27077816

  5. Effect of High Impact or Non-impact Loading Activity on Bone Bending Stiffness and Mineral Density

    Science.gov (United States)

    Liang, Michael T. C.; Arnnud, Sara B.; Steele, Charles R.; Moreno, Alexjandro

    2003-01-01

    Material properties of conical bone, including mineral density (BMD) and its geometry is closely related to its load-carrying capacity. These two primary components determine the strength of conical bone. High impact loading involving acceleration and deceleration movements used in gymnastics induce higher BMD of the affected bone compared to the non-impact acceleration and deceleration movements used in swimming. Study of these two groups of athletes on bone bending stiffness has not been reported. The purpose of this study was to compare differences in bone bending stiffness and BMD between competitive female synchronized swimmers and female gymnasts. Thirteen world class female synchronized swimmers (SYN) and 8 female gymnasts (GYM), mean age 21 +/- 2.9 yr. were recruited for this study. We used a mechanical response tissue analyzer (Gaitscan, NJ) to calculate EI, where E is Young's modulus of elasticity and I is the cross-sectional moment of inertia. EI was obtained from tissue response to a vibration probe placed directly on the skin of the mid-region of tibia and ulna. BMD of the heel and wrist were measured with a probe densitometer (PIXI, Lunor, WI). The SYN were taller than (p < 0.05) the GYM but weighed the same as the GYM. EI obtained from tibia and ulna of the SYN (291 +/- 159 and 41 +/- 19.4, respectively) were not significantly different from thc GYM (285 +/- 140 and 44 +/- 18.3, respectively). BMD of the heel and wrist in GYM were higher than in SYN (p < 0.001). High impact weight-bearing activities promote similar bone strength but greater BMD response than non-impact activities performed in a buoyant environment.

  6. Mesoporous silica coatings for cephalosporin active release at the bone-implant interface

    Science.gov (United States)

    Rădulescu, Dragoş; Voicu, Georgeta; Oprea, Alexandra Elena; Andronescu, Ecaterina; Grumezescu, Valentina; Holban, Alina Maria; Vasile, Bogdan Stefan; Surdu, Adrian Vasile; Grumezescu, Alexandru Mihai; Socol, Gabriel; Mogoantă, Laurenţiu; Mogoşanu, George Dan; Balaure, Paul Cătălin; Rădulescu, Radu; Chifiriuc, Mariana Carmen

    2016-06-01

    In this study, we investigated the potential of MAPLE-deposited coatings mesoporous silica nanoparticles (MSNs) to release Zinforo (ceftarolinum fosmil) in biologically active form. The MSNs were prepared by using a classic procedure with cetyltrimethylammonium bromide as sacrificial template and tetraethylorthosilicate as the monomer. The Brunauer-Emmett-Teller (BET) and transmission electron microscopy (TEM) analyses revealed network-forming granules with diameters under 100 nm and an average pore diameter of 2.33 nm. The deposited films were characterized by SEM, TEM, XRD and IR. Microbiological analyses performed on ceftaroline-loaded films demonstrated that the antibiotic was released in an active form, decreasing the microbial adherence rate and colonization of the surface. Moreover, the in vitro and in vivo assays proved the excellent biodistribution and biocompatibility of the prepared systems. Our results suggest that the obtained bioactive coatings possess a significant potential for the design of drug delivery systems and antibacterial medical-use surfaces, with great applications in bone implantology.

  7. Green Tea and Bone Marrow Transplantation: From Antioxidant Activity to Enzymatic and Multidrug-resistance Modulation.

    Science.gov (United States)

    Peluso, Ilaria; Palmery, Maura; Vitalone, Annabella

    2016-10-25

    Epigallocatechin-3-gallate (EGCG), the main flavonoid of green tea (GT), could play an active role in the prevention of oxidative-stress-related diseases, such as hematologic malignancies. Some effects of EGCG are not imputable to antioxidant activity, but involve modulation of antioxidant enzymes and uric acid (UA) levels. The latter is the major factor responsible of the plasma non-enzymatic antioxidant capacity (NEAC). However, hyperuricemia is a frequent clinical feature caused by tumor lysis syndrome or cyclosporine side effects, both before and after bone marrow transplantation (BMT). Besides this, food-drug interactions could be associated with GT consumption and could have clinical implications. The molecular mechanisms involved in the redox and drug metabolizing/transporting pathways were discussed, with particular reference to the potential role of GT and EGCG in BMT. Moreover, on reviewing data on NEAC, isoprostanes, uric acid, and various enzymes from human studies on GT, its extract, or EGCG, an increase in NEAC, without effect on isoprostanes, and contrasting results on UA and enzymes were observed. Currently, few and contrasting available evidences suggest caution for GT consumption in BMT patients and more studies are needed to better understand the potential impact of EGCG on oxidative stress and metabolizing/transporting systems. PMID:26047551

  8. Apoptosis of bone marrow mesenchymal stem cells caused by homocysteine via activating JNK signal.

    Directory of Open Access Journals (Sweden)

    Benzhi Cai

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs are capable of homing to and repair damaged myocardial tissues. Apoptosis of BMSCs in response to various pathological stimuli leads to the attenuation of healing ability of BMSCs. Plenty of evidence has shown that elevated homocysteine level is a novel independent risk factor of cardiovascular diseases. The present study was aimed to investigate whether homocysteine may induce apoptosis of BMSCs and its underlying mechanisms. Here we uncovered that homocysteine significantly inhibited the cellular viability of BMSCs. Furthermore, TUNEL, AO/EB, Hoechst 333342 and Live/Death staining demonstrated the apoptotic morphological appearance of BMSCs after homocysteine treatment. A distinct increase of ROS level was also observed in homocysteine-treated BMSCs. The blockage of ROS by DMTU and NAC prevented the apoptosis of BMSCs induced by homocysteine, indicating ROS was involved in the apoptosis of BMSCs. Moreover, homocysteine also caused the depolarization of mitochondrial membrane potential of BMSCs. Furthermore, apoptotic appearance and mitochondrial membrane potential depolarization in homocysteine-treated BMSCs was significantly reversed by JNK inhibitor but not p38 MAPK and ERK inhibitors. Western blot also confirmed that p-JNK was significantly activated after exposing BMSCs to homocysteine. Homocysteine treatment caused a significant reduction of BMSCs-secreted VEGF and IGF-1 in the culture medium. Collectively, elevated homocysteine induced the apoptosis of BMSCs via ROS-induced the activation of JNK signal, which provides more insight into the molecular mechanisms of hyperhomocysteinemia-related cardiovascular diseases.

  9. Degradation profile and preliminary clinical testing of a resorbable device for ligation of blood vessels.

    Science.gov (United States)

    Aminlashgari, Nina; Höglund, Odd V; Borg, Niklas; Hakkarainen, Minna

    2013-06-01

    A resorbable device for ligation of blood vessels was developed and tested in vitro to reveal the degradation profile of the device and to predict the clinical performance in terms of adequate mechanical support during a healing period of 1week. In addition, preliminary clinical testing was performed that showed complete hemostasis and good tissue grip of renal arteries in five pigs. The device was made by injection molding of poly(glycolide-co-trimethylene carbonate) triblock copolymer, and it consisted of a case with a locking mechanism connected to a partly perforated flexible band. A hydrolytic degradation study was carried out for 7, 30 and 60days in water and buffer medium, following the changes in mass, water absorption, pH and mechanical properties. A new rapid matrix-free laser desorption ionization-mass spectrometry (LDI-MS) method was developed for direct screening of degradation products released into the degradation medium. The combination of LDI-MS and electrospray ionization-mass spectrometry analyses enabled the comparison of the degradation product patterns in water and buffer medium. The identified degradation products were rich in trimethylene carbonate units, indicating preferential hydrolysis of amorphous regions where trimethylene units are located. The crystallinity of the material was doubled after 60days of hydrolysis, additionally confirming the preferential hydrolysis of trimethylene carbonate units and the enrichment of glycolide units in the remaining solid matrix. The mechanical performance of the perforated band was followed for the first week of hydrolysis and the results suggest that sufficient strength is retained during the healing time of the blood vessels. PMID:23438863

  10. A two-year history of high bone loading physical activity attenuates ethnic differences in bone strength and geometry in pre-/early pubertal children from a low-middle income country.

    Science.gov (United States)

    Meiring, Rebecca M; Avidon, Ingrid; Norris, Shane A; McVeigh, Joanne A

    2013-12-01

    We examined the interplay between ethnicity and weight-bearing physical activity on the content and volumetric properties of bone in a pre- to early pubertal South African Black and White population. Sixty six children [Black boys, 10.4 (1.4)yrs, n=15; Black girls, 10.1 (1.2)yrs, n=27; White boys, 10.1 (1.1)yrs, n=7; White girls, 9.6 (1.3)yrs, n=17] reported on all their physical activities over the past two years in an interviewer administered physical activity questionnaire (PAQ). All participants underwent a whole body and site-specific DXA scan and we also assessed bone structure and estimated bone strength with pQCT. Children were classified as being either high or low bone loaders based on the cohort's median peak bone strain score estimated from the PAQ. In the low bone loading group, Black children had greater femoral neck bone mineral content (BMC) (2.9 (0.08)g) than White children (2.4 (0.11)g; p=0.05). There were no ethnic differences in the high bone loaders for femoral neck BMC. At the cortical site, the Black low bone loaders had a greater radius area (97.3 (1.3) vs 88.8 (2.6)mm(2); p=0.05) and a greater tibia total area (475.5 (8.7) vs. 397.3 (14.0)mm(2); p=0.001) and strength (1633.7 (60.1) vs. 1271.8 (98.6)mm(3); p=0.04) compared to the White low bone loaders. These measures were not different between the Black low and high bone loaders or between the Black and White high bone loaders. In conclusion, the present study shows that there may be ethnic and physical activity associations in the bone health of Black and White pre-pubertal children and further prospective studies are required to determine the possible ethnic specific response to mechanical loading. PMID:24012701

  11. Microgravity Induces Pelvic Bone Loss through Osteoclastic Activity, Osteocytic Osteolysis, and Osteoblastic Cell Cycle Inhibition by CDKN1a/p21

    OpenAIRE

    Blaber, Elizabeth A.; Dvorochkin, Natalya; Lee, Chialing; Alwood, Joshua S.; Yousuf, Rukhsana; Pianetta, Piero; Globus, Ruth K.; Burns, Brendan P.; Almeida, Eduardo A.C.

    2013-01-01

    Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arres...

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

    OpenAIRE

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

    2010-01-01

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

  13. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  14. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Søe, Kent; Andersen, Thomas Levin;

    2014-01-01

    Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast...... recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where...... osteoblasts have to be recruited show the presence of non-degraded demineralized collagen and close cell-collagen interactions, as revealed by electron microscopy, while surface-bound collagen strongly attracts osteoblast lineage cells in a transmembrane migration assay. Compared with other extracellular...

  15. Bone Biopsy

    Science.gov (United States)

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

  16. Fluoride effect on the process of alveolar bone repair in rats: evaluation of activity of MMP-2 and 9

    Directory of Open Access Journals (Sweden)

    Mileni da Silva Fernandes

    2012-09-01

    Full Text Available Objective: The aim of this study was to evaluate comparatively the effect of fluoride (F on the activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9 involved in process of alveolar bone repair. Material and methods: This study used 4 groups of Wistar rats with 80 days of life (n = 160 which received drinking water containing different doses of fluoride (NaF: 5, 15, 50 ppm and deionized water (control throughout the experiment. These animals had their right upper incisors extracted. After extraction, the animals were euthanized at 7, 14, 21 and 30 days and the hemi-maxillae were collected for microscopic analysis (Hematoxylin and Eosin and immunohistochemistry for MMP-9 and zymography (MMP-2 and 9. Results: Microscopically the process of bone repair was similar in all groups, being noted only a delay of the blood clot resorption and bone formation in the group of 50 ppm F. The expression for MMP-9 showed differences between groups only during the initial repair (7 days. However, the zymography showed no significant differences between treated and control groups. Conclusion: Ours results suggest an effect of fluoride on the activity of MMPs 2 and 9 at the initial period of alveolar repair which could be associated to the process of blood clot remission and delay in bone repair. Further studies are needed to establish the relationship between the initial process of resorption of the blood clot, and the involvement of MMPs 2 and 9 and its regulators/tissue inhibitors.

  17. Radiological signs of bone infection and neoplasia

    International Nuclear Information System (INIS)

    Infection of equine bone is relatively common but neoplasia is rare. Infective organisms can center bone by direct contamination through penetrating wounds, spreads from adjacent infected structures or via the circulation as a consequence of septicaemic illness. Heamatogenous osteomyelitis is most likely to occur in young foals, but it has been suggested that in conjuction with a compromise in the vascular supply, bacteraemia may be a contributory factor to the pathogenesis of osteomyelitis of the proximal sesamoid bones in adult horses (Wisner et al. 1991). The radiographic changes associated with bone infection and neoplasia are often neither specific nor definitive. This is because bone has only a limited capacity to react to pathological insult, which is either to proliferate or be resorbed. The proportions in which these two processes occur and the resulting radiographic patterns which develop are as likely to be a reflection of the site of the lesion and the anatomy of the bone involved as to the type of disease which causes them. This means that radiological signs of bone disturbance should always be interpreted in conjuction with all other clinical information available

  18. TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model.

    Science.gov (United States)

    Handschel, Jörg; Wiesmann, Hans Peter; Stratmann, Udo; Kleinheinz, Johannes; Meyer, Ulrich; Joos, Ulrich

    2002-04-01

    Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading. PMID:11922472

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Response Of Mineralizing And Non-Mineralizing Bone Cells To Fluid Flow: An In Vitro Model For Mechanotransruction

    Science.gov (United States)

    Makuch, Lauren A.

    2004-01-01

    Humans reach peak bone mass at age 30. After this point, we lose 1 to 2 percent of bone mass each decade. In the microgravity environment of space, astronauts lose bone mass at an accelerated rate of 1 to 2 percent each month. When astronauts travel to Mars, they may be in space for as long as 3 years. During this time, they may lose about half of their bone mass from weight-bearing bones. This loss may be irreversible. The drastic loss in bone that astronauts experience in space makes them much more vulnerable to fractures. In addition, the corresponding removal of calcium from bone results in higher levels of calcium in the blood, which increases the risk of developing kidney stones. Currently, studies are being conducted which investigate factors governing bone adaptation and mechanotransduction. Bone is constantly adapting in response to mechanical stimuli. Increased mechanical loading stimulates bone formation and suppresses bone resorption. Reduction in mechanical loading caused by bedrest, disuse, or microgravity results in decreased bone formation and possibly increased bone resorption. Osteoblasts and osteoclasts are the two main cell types that participate in bone remodeling. Osteoblasts are anabolic (bone-forming) cells and osteoclasts are catabolic (bone-resorbing) cells. In microgravity, the activity of osteoblasts slows down and the activity of osteoclasts may speed up, causing a loss of bone density. Mechanotransduction, the molecular mechanism by which mechanical stimuli are converted to biochemical signals, is not yet understood. Exposure of cells to fluid flow imposes a shear stress on the cells. Several studies have shown that the shear stress that results from fluid flow induces a cellular response similar to that induced by mechanical loading. Thus, fluid flow can be used as an in vitro model to simulate the mechanical stress that bone cells experience in vivo. Previous in vitro studies have shown that fluid flow induces several responses in

  1. A Modified Rabbit Ulna Defect Model for Evaluating Periosteal Substitutes in Bone Engineering: A Pilot Study

    OpenAIRE

    El Backly, Rania M.; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2015-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked ...

  2. Continuous Digital Light Processing (cDLP): Highly Accurate Additive Manufacturing of Tissue Engineered Bone Scaffolds

    OpenAIRE

    Dean, David; Wallace, Jonathan; Siblani, Ali; Wang, Martha O.; Kim, Kyobum; Mikos, Antonios G.; Fisher, John P.

    2012-01-01

    Highly accurate rendering of the external and internal geometry of bone tissue engineering scaffolds effects fit at the defect site, loading of internal pore spaces with cells, bioreactor-delivered nutrient and growth factor circulation, and scaffold resorption. It may be necessary to render resorbable polymer scaffolds with 50 μm or less accuracy to achieve these goals. This level of accuracy is available using Continuous Digital Light processing (cDLP) which utilizes a DLP® (Texas Instrumen...

  3. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

    Directory of Open Access Journals (Sweden)

    Guang-yu Zhang

    2015-01-01

    Full Text Available MicroRNA-9 (miR-9 has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

  4. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

    Institute of Scientific and Technical Information of China (English)

    Guang-yu Zhang; Jun Wang; Yan-jie Jia; Rui Han; Ping Li; Deng-na Zhu

    2015-01-01

    MicroRNA-9 (miR-9) has been shown to promote the differentiation of bone marrow mesen-chymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study conifrmed that increased autophagic activity improved the efifciency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3)-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Re-sults showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron speciifc enolase and microtubule-associated protein 2 increased in the miR-9+ group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

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

    Directory of Open Access Journals (Sweden)

    KathleenFJanz

    2014-07-01

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

  6. Intracellular glutathione status regulates mouse bone marrow monocyte-derived macrophage differentiation and phagocytic activity

    International Nuclear Information System (INIS)

    Although a redox shift can regulate the development of cells, including proliferation, differentiation, and survival, the role of the glutathione (GSH) redox status in macrophage differentiation remains unclear. In order to elucidate the role of a redox shift, macrophage-like cells were differentiated from the bone marrow-derived monocytes that were treated with a macrophage colony stimulating factor (M-CSF or CSF-1) for 3 days. The macrophagic cells were characterized by a time-dependent increase in three major symptoms: the number of phagocytic cells, the number of adherent cells, and the mRNA expression of c-fms, a M-CSF receptor that is one of the macrophage-specific markers and mediates development signals. Upon M-CSF-driven macrophage differentiation, the GSH/GSSG ratio was significantly lower on day 1 than that observed on day 0 but was constant on days 1-3. To assess the effect of the GSH-depleted and -repleted status on the differentiation and phagocytosis of the macrophages, GSH depletion by BSO, a specific inhibitor of the de novo GSH synthesis, inhibited the formation of the adherent macrophagic cells by the down-regulation of c-fms, but did not affect the phagocytic activity of the macrophages. To the contrary, GSH repletion by the addition of NAC, which is a GSH precursor, or reduced GSH in media had no effect on macrophage differentiation, and led to a decrease in the phagocytic activity. Furthermore, we observed that there is checkpoint that is capable of releasing from the inhibition of the formation of the adherent macrophagic cells according to GSH depletion by BSO. Summarizing, these results indicate that the intracellular GSH status plays an important role in the differentiation and phagocytosis of macrophages

  7. Mound Laboratory activities on the removal of plutonium and uranium from wastewater using bone char

    Energy Technology Data Exchange (ETDEWEB)

    Blane, D.W.; Murphy, E.L.

    1976-09-30

    Pilot plant studies sponsored by the Division of Military Application (DMA) to treat Mound Laboratory's low risk waste streams with bone char columns have been completed. This project was to accomplish the following: (1) acquire engineering data such as flow rates, adsorption capacity, and optimum particle size for designing a tertiary treatment system, and (2) optimize the primary waste treatment process using coagulants and flocculants. Bone char, a natural product made from granulated cattle bone, is a form of calcium hydroxyapatite (Ca/sub 10/(PO/sub 4/)/sub 6/(OH)/sub 2/) and contains a small amount of carbon. It is characterized by a high porosity and good resistance to abrasion and crushing. Because plutonium and other actinides can be precipitated as phosphates from weakly acidic, neutral or alkaline solutions, it appeared possible to use an insoluble phosphate adsorbent such as bone char to remove them from waste streams.

  8. [Clinical usefulness of bone turnover markers in the management of osteoporosis].

    Science.gov (United States)

    Yano, Shozo

    2013-09-01

    Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future. PMID:24369600

  9. Evaluation of the 96/4 PLDLLA polymer resorbable lumbar interbody cage in a long term animal model.

    Science.gov (United States)

    Lazennec, Jean Y; Madi, Abdallah; Rousseau, Marc A; Roger, Bernard; Saillant, Gérard

    2006-10-01

    Arthrodesis using interbody cages has demonstrated high fusion rates. However, permanent cages are exposed to stress-shielding, corrosion, and may require explanation when necessary. Polylactic acid (PLA) bioresorbable cages are developed for avoiding these problems, but significant tissue reaction has been reported with 70/30 PLDLLA in some preclinical animal studies. The objective was to evaluate 96/4 PLDLLA cages in a sheep model over 3 years. Sixteen sheeps underwent one level anterior lumbar interbody fusion using 96/4 PLDLLA cages, filled and surrounded with cancellous bone graft from the iliac crest. Six groups of three animals were killed after 3, 6, 9, 12, 24, and 36 months. Harvested lumbar spine had radiographic, MRI, and CT evaluation and histological analysis. Histological results: cage swelling and slight signs of fragmentation associated to fibrocartilaginous tissue apposition at 3 months; bone remodeling around the cage with direct apposition of the mineralization front at 6 months; active cage degradation and complete fusion around the cage at 9 months; cage fragmentation and partial replacement by bone tissue at 12 months; bone bridges in and around the cage at 24 months; full resorption and intervertebral fusion at 36 months. Radiological results: partial arthrodesis at 3 months; definite peripheral arthrodesis at 6 months; similar aspect at 9 months; significant cage resorption at 12 months; definite inner and outer fusion at 24 months; complete cage resorption and calcification at the location of the cage at 36 months confirmed histological observations. Radiographic, CT scan, MRI, and histological data were consistent for showing progressive resorption of 96/4 PLDLLA, interbody fusion, and bone remodeling, with no significant signs of local intolerance reaction. These results are promising and suggest further development of 96/4 PLDLLA cages. PMID:16736199

  10. The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Sergio Tejero

    2016-01-01

    Full Text Available ABSTRACT Background Nutritional status and daily physical activity (PA may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF. Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral density (BMD were determined by dual energy X-ray absorptiometry and bone metabolism markers ALP, P1NP, PICP, and ß-CrossLaps. PA monitoring was assessed for 5 consecutive days using a portable device. Exercise capacity was also determined. Serum 25-hydroxyvitamin D and vitamin K were also determined in all participants. Results Fifty patients (median age: 24.4 years; range: 16-46 were included. BMI had positive correlation with all BMD parameters, with Spearman’s coefficients ranging from 0.31 to 0.47. Total hip bone mineral density and femoral neck BMD had positive correlation with the daily time spent on moderate PA (>4.8 metabolic equivalent-minutes/day; r=0.74, p7.2 metabolic equivalent-minutes/day; r=0.45 p<0.001, body mass index (r=0.44, p=0.001, and muscle mass in limbs (r=0.41, p=0.004. Levels of carboxy-terminal propeptide of type 1 collagen were positively associated with the daily time spent on moderate (r=0.33 p=0.023 and vigorous PA (r=0.53, p<0.001. Conclusions BMI and the daily time spent on moderate PA were found to be correlated with femoral neck BMD in CF patients. The association between daily PA and biochemical markers of bone formation suggests that the level of daily PA may be linked to bone health in this patient group. Further research is needed to confirm these findings.

  11. Microsphere-integrated gelatin-siloxane hybrid scaffolds for bone tissue engineering :in vitro bioactivity & antibacterial activity

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Microsphere integrated gelatin-siloxane hybrid scaffolds were successfully synthesized by using a combined sol-gel processing,post-gelation soaking and freeze-drying process.A bone-like apatite layer was able to form in the Ca2+-containing porous hybrids upon soaking in a simulated body fluid (SBF) up to 1 day.The rate of gentamicin sulfate (GS) release from the GS-loaded gelatin-siloxane hybrid microsphere became constant after a 4 h burst.The antibacterial activity was assessed by the agar diffusion test (ADT) and the bactericidal effect test.It is evident that the as-synthesized porous scaffolds have excellent bioactivity and antibacterial activity,and may be favorable in bone tissue engineering.

  12. Mitogen activated protein kinase signaling pathways participate in the active principle region of Buyang Huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Jinghui Zheng; Jian Liang; Xin Deng; Xiaofeng Chen; Fasheng Wu; Xiaofang Zhao; Yuan Luo; Lei Fu; Zuling Jiang

    2012-01-01

    Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively. mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction.

  13. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    OpenAIRE

    Anne-Priscille Trouvin; Vincent Goëb

    2010-01-01

    Anne-Priscille Trouvin, Vincent GoëbDepartment of Rheumatology, Rouen University Hospital, Rouen, FranceAbstract: Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG) and receptor activator for nuclear factor-κB (RANK) ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance ...

  14. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation

    OpenAIRE

    Bruscia, Emanuela M.; Price, Joanna E.; Cheng, Ee-chun; Weiner, Scott; Caputo, Christina; Ferreira, Elisa C.; Egan, Marie E.; Krause, Diane S.

    2006-01-01

    Several studies have demonstrated that bone marrow (BM)-derived cells give rise to rare epithelial cells in the gastrointestinal (GI) and respiratory tracts after BM transplantation into myeloablated recipients. We investigate whether, after transplantation of cystic fibrosis transmembrane conductance regulator (CFTR)-positive BM-derived cells, BM-derived GI and airway epithelial cells can provide CFTR activity in the GI tract and nasal epithelium of recipient cystic fibrosis mice. CFTR−/− mi...

  15. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

    OpenAIRE

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-01-01

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent e...

  16. Altered bone marrow activity: potential cause of flase-positive indium-111-labeled leukocyte image patterns in complicated cases of suspected osteomyelitis

    International Nuclear Information System (INIS)

    This paper determines the frequency with which altered bone marrow distribution might cause false-positive In-111-labeled white blood cell (In-111 WBC) localization patterns at suspected sits of osteomyelitis. Bone/bone marrow cultures were used in each of 74 patients to establish the presence of infection. Thirty-eight patients had nonunited fractures, 26 had painful prostheses, and 10 had prior osteomyelitis. Tc-99 m albumin colloid (Tc-99 m AC) bone marrow imaging was done in 18 patients initially considered to have osteomyelitis by In-111 WBC/Tc-99 m MDP imaging. All 18 had undergone prior internal fixation, bone grafting, or prosthesis removal. Studies were defined positive for osteomyelitis when In-111 WBC activity exceeded Tc-99 m AC activity in extent or focal intensity (discordant)

  17. Evaluation of (antigenotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

    Directory of Open Access Journals (Sweden)

    Fernando Márlisson de Queiroz

    2013-03-01

    Full Text Available Phyllanthus niruri L. (Euphorbiaceae, known as "quebra-pedra" (Portuguese for "stonebreaker", is an herb used for kidney disorders. In light of its frequent use by the population, the present study aimed to investigate the genotoxic, antigenotoxic and cytotoxic activities of a standardized P. niruri extract in bone marrow rats. Three groups of 12 animals were treated daily by gavage over a period of 30 days, with 50, 150 or 250 mg/kg of P. niruri extract aqueous solution. The control group (n = 12 received tap water. At the end of treatment (day 31, groups were divided into two minor subgroups (n=6/group and received cyclophosphamide (50 mg/kg, i.p. or saline 0.9% (i.p.. After 24 hours, we evaluated the frequency of micronucleated polychromatic erythrocytes for each animal (MNPCE at 1000 PCE. Cytotoxicity was evaluated with the PCE/NCE ratio (NEC = normochromatic erythrocytes. General toxicity was assessed during treatment using the parameters of body weight gain, ration and water consumption. The dry extract did not provoke changes in body weight, weight gain, ration and water intake or changes in the frequency of MNPCE or cytotoxicity in bone marrow. We propose that the P. niruri extract used here showed no genotoxic, antigenotoxic and cytotoxic activities under the experimental conditions.Phyllanthus niruri L. (Euphorbiaceae, conhecida como "quebra-pedra", é uma planta medicinal utilizada frequentemente pela população no tratamento de problemas renais. Foram avaliadas as atividades genotóxicas, antigenotóxicas e citotóxicas de um extrato padronizado dessa espécie em ratos. Três grupos de doze animais foram tratados durante trinta dias, por gavagem, com 50, 150 ou 250 mg/kg/dia de solução aquosa do extrato de P. niruri e um grupo controle (n=12 recebeu água destilada pela mesma via. No final do tratamento os grupos foram divididos em dois subgrupos (6 animais/grupo e receberam uma dose única de ciclofosfamida (50 mg/kg, i.p. ou de

  18. Abnormal extraosseous activity in both lungs and stomach in pre-transplant 99mTc-MDP bone scan disappearing after renal transplant

    International Nuclear Information System (INIS)

    A chronic kidney disease male patient presenting with bone pains, fever, weakness, and clinically ascites was subjected to four technetium-99m-methylene diphosphonate (99mTc-MDP) bone scans, two before renal transplant and two after renal transplants. Pretransplant bone scan revealed metabolic bone disease with focal insufficiency fractures. Marked extraosseous activity in both lungs and stomach was also visualized. On regular hemodialysis (HD) after 4 months, repeat pretransplant bone scan showed persistent uptake in lungs and stomach, representing altered calcium metabolism with microcalcifications. He underwent human leukocyte antigen (HLA) matched live donor renal transplantation, started on immune-suppression and steroids. Posttransplant bone scan at 20 days revealed no definite interval change, but bone scan performed approximately 17 months posttransplant showed resolving metabolic bone disease and the tracer uptake in the lungs and stomach was no more visualized. Patient clinically followed-up until the date (February 2013) is asymptomatic with serum creatinine of 1.5 mg/dl, no bone scan done. (author)

  19. Bone markers and osteoporosis therapy

    Directory of Open Access Journals (Sweden)

    Francisco Bandeira

    2014-07-01

    Full Text Available Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually. Bone turn over markers (BTM are frequently used in clinical trials and to provide valid information about the effectiveness of osteoporosis treatment, reflecting the state of bone metabolism and its response to treatment, although they are not useful alone to estimate bone loss. In this review the behavior of BTM from different clinical trials or different osteoporotic drugs will be addressed.

  20. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  1. Influence of ethylene oxide sterilization on the activity of native reindeer bone morphogenetic protein

    OpenAIRE

    Pekkarinen, T. (Tarmo); Hietala, O.; Lindholm, T. S.; Jalovaara, P.

    2003-01-01

    We studied the effects of ethylene oxide sterilization (Steri-Vac 4XL, temperature 29°C, exposure time 4 h 10 min, ethylene oxide concentration 860 mg/l) on the osteoinductivity of partially purified native reindeer bone morphogenetic protein (BMP) in a hind leg muscle pouch model of male NMRI mice. BMP was administered in implants containing 3 mg in a collagen carrier. Implants without sterilization and without BMP served as controls. New bone formation was evaluated based on the calcium yie...

  2. Bone mineral density changes in protease inhibitor-sparing vs. nucleoside reverse transcriptase inhibitor-sparing highly active antiretroviral therapy: data from a randomized trial

    DEFF Research Database (Denmark)

    Hansen, Ann-Brit Eg; Obel, N; Nielsen, H;

    2011-01-01

    The aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIV-infected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART).......The aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIV-infected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART)....

  3. TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Weisse, N; Jeraj, R [Department of Medical Physics, University of Wisconsin, Madison, WI (United States)

    2014-06-15

    Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUVmean, SUVmax, and SUVCV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUVmean, SUVmax, and SUVCV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUVmean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUVmax correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

  4. TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

    International Nuclear Information System (INIS)

    Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUVmean, SUVmax, and SUVCV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUVmean, SUVmax, and SUVCV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUVmean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUVmax correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

  5. Effect of local hemostatics on bone induction in rats: a comparative study of bone wax, fibrin-collagen paste, and bioerodible polyorthoester with and without gentamicin

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G;

    1992-01-01

    evaluated by light microscopy and 85Sr uptake analyses. Non-absorbable bone wax of 88% beeswax and absorbable bovine fibrin-collagen paste both significantly inhibited osteoinduction, whereas a bioerodible polyorthoester drug delivery system with or without 4% gentamicin did not. Bone wax was not absorbed...... and induced a chronic foreign body reaction. Fibrin-collagen paste induced less inflammation with numerous monocytes and macrophages with engulfed material. Bioerodible polyorthoester caused a very moderate tissue reaction and was mostly resorbed at week 4....

  6. Preparation and Characterization of Biomimetic Hydroxyapatite-Resorbable Polymer Composites for Hard Tissue Repair

    Science.gov (United States)

    Hiebner, Kristopher Robert

    Autografts are the orthopedic "gold standard" for repairing bone voids. Autografts are osteoconductive and do not elicit an immune response, but they are in short supply and require a second surgery to harvest the bone graft. Allografts are currently the most common materials used for the repair of segmental defects in hard tissue. Unlike autografts, allografts can cause an undesirable immune response and the possibility of disease transmission is a major concern. As an alternative to the above approaches, recent research efforts have focused on the use of composite materials made from hydroxyapatite (HA) and bioresorbable polymers, such as poly-L-lactide (PLLA). Recent results have shown that the surface hydroxides on HA can initiate the ring opening polymerization (ROP) of L-lactide and other lactones creating a composite with superior interfacial strength. This thesis demonstrates that the surface of porous biologically derived HA substrates, such as coralline HA and trabecular bone, can be used to initiate the ROP of L-lactide and other lactones from the vapor phase. This process increases the strength of the porous scaffold through the deposition of a thin, uniform polymer coating, while maintaining the porous structure. The kinetics of the chemical vapor deposition polymerization (CVDP) are described using a quartz crystal microbalance (QCM). The reaction temperature and monomer vapor pressure are found to affect the rate of the polymerization. Also described in this thesis is the preparation of a porous polymer scaffold that mimics the structure of demineralized bone matrix (DBM). This demineralized bone matrix simulant (DBMS) is created using anorganic bovine bone as a template to initiate the polymerization of various lactones, followed by the removal of the HA scaffold. This material retained its shape and exhibits mechanical properties superior to DBM. Finally it is shown that HA can be used to initiate the ROP of a-caprolactam and the biocompatibility

  7. Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Guo-yong Yu

    2016-01-01

    Full Text Available Naringin is a major flavonoid found in grapefruit and is an active compound extracted from the Chinese herbal medicine Rhizoma Drynariae. Naringin is a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of naringin involves the Notch signaling pathway. Rat bone marrow stromal cells (BMSCs were cultured in osteogenic medium containing-naringin, with or without DAPT (an inhibitor of Notch signaling, the effects on ALP activity, calcium deposits, osteogenic genes (ALP, BSP, and cbfa1, adipogenic maker gene PPARγ2 levels, and Notch expression were examined. We found that naringin dose-dependently increased ALP activity and Alizarin red S staining, and treatment at the optimal concentration (50 μg/mL increased mRNA levels of osteogenic genes and Notch1 expression, while decreasing PPARγ2 mRNA levels. Furthermore, treatment with DAPT partly reversed effects of naringin on BMSCs, as judged by decreases in naringin-induced ALP activity, calcium deposits, and osteogenic genes expression, as well as upregulation of PPARγ2 mRNA levels. These results suggest that the osteogenic effect of naringin partly involves the Notch signaling pathway.

  8. Naringin Stimulates Osteogenic Differentiation of Rat Bone Marrow Stromal Cells via Activation of the Notch Signaling Pathway.

    Science.gov (United States)

    Yu, Guo-Yong; Zheng, Gui-Zhou; Chang, Bo; Hu, Qin-Xiao; Lin, Fei-Xiang; Liu, De-Zhong; Wu, Chu-Cheng; Du, Shi-Xin; Li, Xue-Dong

    2016-01-01

    Naringin is a major flavonoid found in grapefruit and is an active compound extracted from the Chinese herbal medicine Rhizoma Drynariae. Naringin is a potent stimulator of osteogenic differentiation and has potential application in preventing bone loss. However, the signaling pathway underlying its osteogenic effect remains unclear. We hypothesized that the osteogenic activity of naringin involves the Notch signaling pathway. Rat bone marrow stromal cells (BMSCs) were cultured in osteogenic medium containing-naringin, with or without DAPT (an inhibitor of Notch signaling), the effects on ALP activity, calcium deposits, osteogenic genes (ALP, BSP, and cbfa1), adipogenic maker gene PPARγ2 levels, and Notch expression were examined. We found that naringin dose-dependently increased ALP activity and Alizarin red S staining, and treatment at the optimal concentration (50 μg/mL) increased mRNA levels of osteogenic genes and Notch1 expression, while decreasing PPARγ2 mRNA levels. Furthermore, treatment with DAPT partly reversed effects of naringin on BMSCs, as judged by decreases in naringin-induced ALP activity, calcium deposits, and osteogenic genes expression, as well as upregulation of PPARγ2 mRNA levels. These results suggest that the osteogenic effect of naringin partly involves the Notch signaling pathway. PMID:27069482

  9. Proliferative activity of vervet monkey bone marrow-derived adherent cells

    International Nuclear Information System (INIS)

    Vervet monkey bone marrow-derived adherent cell population cultured in Fischer's medium supplemented with 12.5% fetal calf serum and 12.5% horse serum consists of two cell shapes: fusiform (type I) and polygonal (type II). Limiting-dilution cloning of the cells suggested that the two morphologically distinct cell types belong to the same cellular system even though they differ in their proliferative capabilities. The labeling index of type II cells, as measured by autoradiography, was found to be consistently lower than that of type I cells. It is probable that these two phenotypes represent different stages of differentiation, where progenitor type I gives rise to type II cells. The bone marrow-derived adherent cells were found to be cytokinetically at rest in vivo, using the thymidine suicide test, and relatively radioresistant with a D0 = 2.1 Gy and n = 2.36 at the time of explantation from the bone. Furthermore, in culture these cells are characterized by a relatively long cell cycle of 60 h, where the length of the S phase is 30 h, G2 is 12 h, M is 6 h, and G1 is 12 h. Thus, the vervet monkey bone marrow-derived adherent cells represent a cell population with a low turnover rate both in vivo and in vitro

  10. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal reorganizat...

  11. Topical treatment with Xiaozheng Zhitong Paste alleviates bone cancer pain by inhibiting proteinase-activated receptor 2 signaling pathway.

    Science.gov (United States)

    Bao, Yanju; Wang, Gaimei; Gao, Yebo; Du, Maobo; Yang, Liping; Kong, Xiangying; Zheng, Honggang; Hou, Wei; Hua, Baojin

    2015-09-01

    Herbal analgesic Xiaozheng Zhitong Paste (XZP) and related modifications are often used in traditional Chinese medicine to manage cancer pain. However, its underlying mechanism remains unknown. To investigate the effects and mechanism of XZP on bone cancer pain in a rat model of breast cancer-induced bone pain, a bone cancer pain model was established by inoculating Walker 256 cells into Wistar rats. Bone cancer-bearing rats were topically treated with different doses of XZP or injected with 5 mg/kg of osteoprotegerin (OPG) as positive control. Bone destruction, bone mineral content (BMC) and bone mineral density (BMD) were analyzed by radiology. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were examined to determine pain levels. Trypsin, TNF-α and IL-1β serum levels were determined using enzyme-linked immunosorbent assay (ELISA). Central sensitization markers such as c-Fos, GFAP, IBA1 and CGRP, as well as proteinase-activated receptor 2 (PAR2) signaling pathway mediators such as PAR2, PKC-γ, PKA and TRPV1, were determined by quantitative RT-PCR and western blotting assay. XZP treatment significantly mitigated bone cancer-related nociceptive behavior, bone damage, BMC and BMD; and decreased radiological scores in rats. XZP treatment significantly inhibited IBA1, GFAP, c-Fos and CGRP expressions in the spinal cord; and significantly mitigated trypsin, TNF-α and IL-1β serum levels. Furthermore, PAR2, PKC-γ, PKA and TRPV1 relative mRNA levels and protein expression in bone lesions were significantly reduced in rats treated with XZP. XZP significantly alleviates breast cancer-induced bone pain by inhibiting the PAR2 signaling pathway. PMID:26133236

  12. Comparative outcomes of active and passive hearing devices by transcutaneous bone conduction.

    Science.gov (United States)

    Zernotti, Mario Emilio; Di Gregorio, Maria Fernanda; Galeazzi, Pablo; Tabernero, Paola

    2016-06-01

    Conclusion Bonebridge (BB) and Sophono (SP) devices improved hearing; with the BB implant showing a better performance at medium and high frequencies. Furthermore, the BB, as an active implant, showed higher functional gain and increased time of use, when compared to the SP, a passive system. Objectives This study aims to compare surgical and audiological outcomes of SP and BB devices in order to assess and further differentiate the indication criteria. Methods Fourteen patients with conductive and mixed hearing loss were evaluated pre- and post-operatively (BB or SP) (period 2013-2014). Age, gender, surgical history, cause and type of hearing loss, implant use per day, levels of bone and air conduction, and functional gain were recorded. Data was analysed by Wilcoxon singed-rank and Wilcoxon rank-sum tests. Results Fourteen patients (BB; n = 10 and SP; n = 4) with an average age = 25.42 years (CI95 = 12.41-38.43) were evaluated. The gender relation was equal (1:1), with pre-implantation osseous thresholds of 20.42 dB (CI95 = 11.15-29.69), and pre-implantation aerial thresholds of 70.83 dB (CI95 = 62.52-79.14). The SP wearing time was significantly lower than that of the BB (SP = 7-10 h/day, BB = 8-12 h/day; p = 0.0323). The functional gain did not differ significantly between the two devices (BB = 40.00 ± 13.19 dB, SP = 34.06 ± 15.63 dB; p = 0.3434), but a significant improvement from pre- to post-implantation was observed (p < 0.05). BB and SP decreased auditory thresholds at 1 and 2 kHz (< 0.01), respectively. The BB even significantly decreased thresholds at 0.5 kHz (p = 0.0140) and 4 kHz (p < 0.0001). No relevant surgical complications were found. PMID:26981711

  13. Small oscillatory accelerations, independent of matrix deformations, increase osteoblast activity and enhance bone morphology.

    Directory of Open Access Journals (Sweden)

    Russell Garman

    Full Text Available A range of tissues have the capacity to adapt to mechanical challenges, an attribute presumed to be regulated through deformation of the cell and/or surrounding matrix. In contrast, it is shown here that extremely small oscillatory accelerations, applied as unconstrained motion and inducing negligible deformation, serve as an anabolic stimulus to osteoblasts in vivo. Habitual background loading was removed from the tibiae of 18 female adult mice by hindlimb-unloading. For 20 min/d, 5 d/wk, the left tibia of each mouse was subjected to oscillatory 0.6 g accelerations at 45 Hz while the right tibia served as control. Sham-loaded (n = 9 and normal age-matched control (n = 18 mice provided additional comparisons. Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls. Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17% and connectivity density (33%, and significantly smaller trabecular spacing (-6% and structural model index (-11%. These in vivo data indicate that mechanosensory elements of resident bone cell populations can perceive and respond to acceleratory signals, and point to an efficient means of introducing intense physical signals into a biologic system without putting the matrix at risk of overloading. In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism.

  14. Tissue reaction and material characteristics of four bone substitutes

    DEFF Research Database (Denmark)

    Jensen, S S; Aaboe, M; Pinholt, E M; Hjørting-Hansen, E; Melsen, F; Ruyter, I E

    1996-01-01

    and Interpore 500 HA/CC) were implanted into 5-mm bur holes in rabbit tibiae. There was no difference in the amount of newly formed bone around the four biomaterials. Interpore 500 HA/CC resorbed completely, whereas the other three biomaterials did not undergo any detectable biodegradation. Bio......-Oss was osseointegrated to a higher degree than the other biomaterials. Material characteristics obtained by diffuse reflectance infrared Fourier transform spectrometry analysis and energy-dispersive spectrometry did not explain the differences in biologic behavior....

  15. Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs

    DEFF Research Database (Denmark)

    Baad-Hansen, Thomas Einer; Overgaard, S; Lind, M;

    2007-01-01

    weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a......Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules...... surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three...

  16. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  17. Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

    Science.gov (United States)

    Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

    2006-06-01

    Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts. PMID:16740479

  18. Zygomatic implants: the impact of zygoma bone support on biomechanics.

    Science.gov (United States)

    Romeed, Shihab A; Malik, Raheel; Dunne, Stephen M

    2014-06-01

    Maxillectomy and severely resorbed maxilla are challenging to restore with provision of removable prostheses. Dental implants are essential to restore esthetics and function and subsequently quality of life in such group of patients. Zygomatic implants reduce the complications associated with bone grafting procedures and simplify the rehabilitation of atrophic maxilla and maxillectomy. The purpose of this study was to compare, by means of 3-dimensional finite element analysis, the impact of different zygomatic bone support (10, 15, and 20 mm) on the biomechanics of zygomatic implants. Results indicated that maximum stresses within the fixture were increased by 3 times when bone support decreased from 20 to 10 mm and were concentrated at the fixture/bone interface. However, stresses within the abutment screw and the abutment itself were not significantly different regardless of the bone support level. Supporting bone at 10 mm sustained double the stresses of 15 and 20 mm. Fixture's deflection was decreased by 2 to 3 times when bone support level increased to 15 mm and 20 mm, respectively. It was concluded that zygomatic bone support should not be less than 15 mm, and abutment screw is not at risk of fracture regardless of the zygomatic bone support. PMID:24914908

  19. Bone stress injuries

    International Nuclear Information System (INIS)

    Bone stress injuries are due to cyclical overuse of the bone. They are relatively common in athletes and military recruits but also among otherwise healthy people who have recently started new or intensive physical activity. Diagnosis of bone stress injuries is based on the patient's history of increased physical activity and on imaging findings. The general symptom of a bone stress injury is stress-related pain. Bone stress injuries are difficult to diagnose based only on a clinical examination because the clinical symptoms may vary depending on the phase of the pathophysiological spectrum in the bone stress injury. Imaging studies are needed to ensure an early and exact diagnosis, because if the diagnosis is not delayed most bone stress injuries heal well without complications

  20. In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil

    Science.gov (United States)

    Coronado-Cerda, Erika Evangelina; Franco-Molina, Moisés Armides; Mendoza-Gamboa, Edgar; Prado-García, Heriberto; Rivera-Morales, Lydia Guadalupe; Zapata-Benavides, Pablo; Rodríguez-Salazar, María del Carmen; Caballero-Hernandez, Diana; Tamez-Guerra, Reyes Silvestre; Rodríguez-Padilla, Cristina

    2016-01-01

    Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable leukocyte extract (bDLE) or IMMUNEPOTENT CRP® (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients. PMID:27191003

  1. Physical activity and bone mineral accrual in boys with different body mass parameters during puberty: a longitudinal study.

    Directory of Open Access Journals (Sweden)

    Donvina Vaitkeviciute

    Full Text Available The aim of our longitudinal study was to investigate the relationships between physical activity and bone mass in boys with different body mass status during the years surrounding pubertal growth spurt. Two hundred and six boys entering puberty took part in this study. The subjects were divided into underweight (BMI 26.02 groups at baseline according to age related categories. Whole-body DXA scans were performed at baseline, after 12 and 24 months to assess body composition (lean body mass, fat mass, and total body (TB, lumbar spine (LS and femoral neck (FN bone mineral density (BMD parameters. Physical activity was measured by 7-day accelerometry. For longitudinal analysis, multilevel fixed effects regression models were constructed. Biological age, height and lean body mass had an effect for explanation of TB BMD, FN BMD and LS BMD. Moderate to vigorous physical activity (MVPA, vigorous physical activity (VPA and sedentary time (SED had the significant effect only on FN BMD. Being an underweight boy at the baseline indicated greater chance (p<0.01 to have lower TB BMD in the future (2 years at follow up development, compared to normal weight (estimates = -0.038, overweight (estimates = -0.061 and obese boys (estimates = -0.106.

  2. Functional and psychological impact of nasal bone fractures sustained during sports activities: A survey of 87 patients.

    Science.gov (United States)

    Lennon, Paul; Jaber, Sam; Fenton, John E

    2016-08-01

    Nasal bone fractures that require reduction are a common sequela of sports injuries. We conducted a survey to ascertain the outcomes of patients who had experienced a nasal bone fracture and who subsequently underwent manipulation under anesthesia. We reviewed data on 217 nasal bone fractures that had been seen at our institution over a 3-year period. Of these, 133 (61.3%) had occurred as a result of a sports activity. Thirty of the 133 patients (22.6%) had been managed conservatively, while the other 103 (77.4%) had undergone manipulation under anesthesia. We were able to contact 87 of the 103 patients (84.5%) by telephone, who served as the study population. The most common sports associated with these 87 injuries were hurling (n = 26; 29.9%), rugby (n = 22; 25.3%), Gaelic football (n = 20; 23.0%), and soccer (n = 13; 14.9%). Patients who had undergone treatment within 2 weeks were significantly more satisfied with their outcome than were those who had been treated later (p performance in their sport; 12 (13.8%) described a fear of reinjury when they returned to play, 7 (8.0%) experienced functional problems, 3 (3.4%) complained of diminished performance, and 4 others (4.6%) quit playing contact sports altogether. To the best of our knowledge, our study is the first to demonstrate that a fracture of the nasal bones may have a notable psychological impact on an athlete and that it can lead to diminished performance or a complete withdrawal from contact sports. PMID:27551843

  3. Aromatic amino acid activation of signaling pathways in bone marrow mesenchymal stem cells depends on oxygen tension.

    Directory of Open Access Journals (Sweden)

    Mona El Refaey

    Full Text Available The physiologic oxygen pressures inside the bone marrow environment are much lower than what is present in the peripheral circulation, ranging from 1-7%, compared to values as high as 10-13% in the arteries, lungs and liver. Thus, experiments done with bone marrow mesenchymal stem cells (BMMSCs using standard culture conditions may not accurately reflect the true hypoxic bone marrow microenvironment. However, since aging is associated with an increased generation of reactive oxygen species, experiments done under 21%O2 conditions may actually more closely resemble that of the aging bone marrow environment. Aromatic amino acids are known to be natural anti-oxidants. We have previously reported that aromatic amino acids are potent agonists for stimulating increases in intracellular calcium and phospho-c-Raf and in promoting BMMSC differentiation down the osteogenic pathway. Our previous experiments were performed under normoxic conditions. Thus, we next decided to compare a normoxic (21% O2 vs. a hypoxic environment (3% O2 alone or after treatment with aromatic amino acids. Reverse-phase protein arrays showed that 3% O2 itself up-regulated proliferative pathways. Aromatic amino acids had no additional effect on signaling pathways under these conditions. However, under 21%O2 conditions, aromatic amino acids could now significantly increase these proliferative pathways over this "normoxic" baseline. Pharmacologic studies are consistent with the aromatic amino acids activating the extracellular calcium-sensing receptor. The effects of aromatic amino acids on BMMSC function in the 21% O2 environment is consistent with a potential role for these amino acids in an aging environment as functional anti oxidants.

  4. A Humanized Mouse Identifies the Bone Marrow as a Niche with Low Therapeutic IgG Activity

    Directory of Open Access Journals (Sweden)

    Anja Lux

    2014-04-01

    Full Text Available Genetic differences between humans and in vivo model systems, including mice and nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G (IgG activity in humans and understand the molecular and cellular mechanisms underlying that activity. To bridge this gap, we established a small-animal model system that allowed us to study human IgG effector functions in the context of an intact human immune system without the interference of murine Fcγ receptors expressed on mouse innate immune effector cells in vivo. Using a model of B cell depletion with different human IgG variants that recognize CD20, we show that this humanized mouse model can provide unique insights into the mechanism of human IgG activity in vivo. Importantly, these studies identify the bone marrow as a niche with low therapeutic IgG activity.

  5. Molecular and cellular basis of bone resorption.

    Science.gov (United States)

    Gruber, Reinhard

    2015-02-01

    Osteoclast research has an exciting history and a challenging future. More than 3 decades ago, it became evident that bone-resorbing osteoclasts are of hematopoietic origin and are ultimately linked to the "basic multicellular unit," where they team up with the other cell types, including bone-forming osteoblasts. Since 2 decades, we have learned about the signaling pathways controlling genes relevant for osteoclastogenesis and bone resorption. It took another decade until the hypothesized "osteoclast differentiation" factor was discovered and was translated into an approved pharmacologic strategy. Here, the focus is on another molecular target, cathepsin K, a cysteine protease being released by the osteoclast into the resorption compartment. Genetic deletion and pharmacological blocking of cathepsin K reduces bone resorption but with ongoing bone formation. This observation not only holds great promise to become a new pharmacologic strategy, but it also provides new insights into the coordinated work of cells in the "basic multicellular unit" and thus, bridges the history and future of osteoclast research. This article is a short primer on osteoclast biology for readers of the special issue on odanacatib, a cathepsin K inhibitor. PMID:25223736

  6. Transforming growth factor-β inhibits CCAAT/enhancer-binding protein expression and PPARγ activity in unloaded bone marrow stromal cells

    International Nuclear Information System (INIS)

    The molecular mechanisms regulating the adipogenic differentiation of bone marrow stromal cells in vivo remain largely unknown. In this study, we investigated the regulatory effects of transforming growth factor beta-2 (TGF-β2) on transcription factors involved in adipogenic differentiation induced by hind limb suspension in rat bone marrow stromal cells in vivo. Time course real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis of gene expression showed that skeletal unloading progressively increases the expression of CCAAT/enhancer-binding protein (C/EBP)α and C/EBPβ α at 5 days in bone marrow stromal cells resulting in increased peroxisome proliferator-activated receptor γ (PPARγ2) transcripts at 7 days. TGF-β2 administration in unloaded rats corrected the rise in C/EBPα and C/EBPβ transcripts induced by unloading in bone marrow stromal cells. This resulted in inhibition of PPARγ2 expression that was associated with increased Runx2 expression. Additionally, the inhibition of C/EBPα and C/EBPβ expression by TGF-β2 was associated with increased PPARγ serine phosphorylation in bone marrow stromal cells, a mechanism that inhibits PPARγ transactivating activity. The sequential inhibitory effect of TGF-β2 on C/EBPα, C/EBPβ, and PPARγ2 resulted in reduced LPL expression and abolition of bone marrow stromal cell adipogenic differentiation, which contributed to prevent bone loss induced by skeletal unloading. We conclude that TGF-β2 inhibits the excessive adipogenic differentiation of bone marrow stromal cells induced by skeletal unloading by inhibiting C/EBPα, C/EBPβ, and PPARγ expression and activity, which provides a sequential mechanism by which TGF-β2 regulates adipogenic differentiation of bone marrow stromal cells in vivo

  7. Portrayal and management of a rarely seen alveolar bone resorption pattern mimicking the Combination Syndrome: a clinical report

    OpenAIRE

    Piskin, Bulent; Sipahi, Cumhur; Emir, Faruk; Ayyıldız, Simel; Avsever, İsmail Hakan; Uyar, Alper

    2014-01-01

    ABSTRACTTreatment of severely resorbed edentulous alveolar ridges is still a challenging topic of prosthodontics. Combination Syndrome is one of the most remarkable intraoral manifestations of excessive alveolar bone resorption which may be observed at the denture wearing patients with complete edentulous maxilla and bilateral partial edentulous mandibula. Since its first recognition in 1972, the major symptoms and morphological features of the Combination Syndrome such as enlarged maxillary ...

  8. Improvement of in vitro physicochemical properties and osteogenic activity of calcium sulfate cement for bone repair by dicalcium silicate

    International Nuclear Information System (INIS)

    Highlights: • Dicalcium silicate can improve osteogenic activity of calcium sulfate cement. • The higher the calcium sulfate content, the shorter the setting time in the composite cement. • The results were useful for designing calcium-based cement with optimal properties. -- Abstract: An ideal bone graft substitute should have the same speed of degradation as formation of new bone tissue. To improve the properties of calcium sulfate hemihydrate (CSH) featured for its rapid resorption, a low degradation material of dicalcium silicate (DCS) was added to the CSH cement. This study examined the effect of DCS (20, 40, 60 and 80 wt%) on the in vitro physicochemical properties and osteogenic activities of the calcium-based composite cements. The diametral tensile strength, porosity and weight loss of the composite cements were evaluated before and after soaking in a simulated body fluid (SBF). The osteogenic activities, such as proliferation, differentiation and mineralization, of human mesenchymal stem cells (hMSCs) seeded on cement surfaces were also examined. As a result, the greater the DCS amount, the higher the setting time was in the cement. Before soaking in SBF, the diametral tensile strength of the composite cements was decreased due to the introduction of DCS. On 180-day soaking, the composite cements containing 20, 40, 60 and 80 wt% DCS lost 80%, 69%, 61% and 44% in strength, respectively. Regarding in vitro bioactivity, the DCS-rich cements were covered with clusters of apatite spherulites after soaking for 7 days, while there was no formation of apatite spherulites on the CSH-rich cement surfaces. The presence of DCS could reduce the degradation of the CSH cements, as evidenced in the results of weight loss and porosity. More importantly, DCS may promote effectively the cell proliferation, proliferation and mineralization. The combination of osteogenesis of DCS and degradation of CSH made the calcium-based composite cements an attractive choice for

  9. An in vivo assessment of muscular activity and the importance of electrical phenomena in bone remodelling.

    OpenAIRE

    Mcdonald, F.; Houston, W J

    1990-01-01

    Modified orthopaedic pins were placed close to the medial and distal epiphyses of the tibia in 4 anaesthetised rabbits, in order to allow the application of controlled external loading cycles. Rosette strain gauges were placed at midshaft level, where the greatest compressive and tensile strains were expected during loading. Two weeks later, following stabilisation of the pins by bone healing, the animals were anaesthetised again and silver-silver chloride electrodes were attached close to th...

  10. Chemically-Conjugated Bone Morphogenetic Protein-2 on Three-Dimensional Polycaprolactone Scaffolds Stimulates Osteogenic Activity in Bone Marrow Stromal Cells

    OpenAIRE

    Zhang, Huina; Migneco, Francesco; Lin, Chia-Ying; Hollister, Scott J.

    2010-01-01

    Poly(ε-caprolactone) (PCL) has received considerable attention in bone tissue engineering. However, the lack of osteoinductive ability of PCL limits its application. The aim of this study was to directly attach bone morphogenetic protein-2 (BMP-2) to PCL scaffolds by a crosslinking conjugation method and to investigate whether the bound BMP-2 maintained bioactivity in vitro. Immunofluorescent staining against BMP-2 and quantitative enzyme-linked immunosorbent assay measurements demonstrated t...

  11. Structural changes and biological responsiveness of an injectable and mouldable monetite bone graft generated by a facile synthetic method.

    Science.gov (United States)

    Cama, G; Gharibi, B; Knowles, J C; Romeed, S; DiSilvio, L; Deb, S

    2014-12-01

    Brushite (dicalcium phosphate dihydrate) and monetite (dicalcium phosphate anhydrous) are of considerable interest in bone augmentation owing to their metastable nature in physiological fluids. The anhydrous form of brushite, namely monetite, has a finer microstructure with higher surface area, strength and bioresorbability, which does not transform to the poorly resorbable hydroxyapatite, thus making it a viable alternative for use as a scaffold for engineering of bone tissue. We recently reported the formation of monetite cements by a simple processing route without the need of hydrothermal treatment by using a high concentration of sodium chloride in the reaction mix of β-tricalcium phosphate and monocalcium phosphate monohydrate. In this paper, we report the biological responsiveness of monetite formed by this method. The in vitro behaviour of monetite after interaction and ageing both in an acellular and cellular environment showed that the crystalline phase of monetite was retained over three weeks as evidenced from X-ray diffraction measurements. The crystal size and morphology also remained unaltered after ageing in different media. Human osteoblast cells seeded on monetite showed the ability of the cells to proliferate and express genes associated with osteoblast maturation and mineralization. Furthermore, the results showed that monetite could stimulate osteoblasts to undergo osteogenesis and accelerate osteoblast maturation earlier than cells cultured on hydroxyapatite scaffolds of similar porosity. Osteoblasts cultured on monetite cement also showed higher expression of osteocalcin, which is an indicator of the maturation stages of osteoblastogenesis and is associated with matrix mineralization and bone forming activity of osteoblasts. Thus, this new method of fabricating porous monetite can be safely used for generating three-dimensional bone graft constructs. PMID:25297314

  12. [Morphological analysis of bone dynamics and metabolic bone disease. Histomorphometric concepts of bone remodeling and modeling].

    Science.gov (United States)

    Takahashi, Hideaki E

    2011-04-01

    In tissue level turnover of bone cells, bone remodeling shows a sequential events of activation, resorption, reversal and formation. This may be observed as secondary osteons in the cortical bone and trabecular packets in the cancellous bone. Microcracks are repaired by targeted remodeling, and calcium is released by non-targeted remodeling. In macromodeling, a macroscopic size of a bone increases with growth, without changing its basic figure. In micromodelimg, a shift of trabecula, a minishift, is biomechnically controlled. New lamellar bone is added parallel to compressive and tensile force, and bone resorption occurs at the opposite surface of formation. In minimodeling new lamellar bone is formed with a sequence of activation, then directly formation, without scalloping at the cement line between newly formed bone and its basic bone. PMID:21447918

  13. The feasibility of in vivo quantification of bone-fluorine in humans by delayed neutron activation analysis: a pilot study

    International Nuclear Information System (INIS)

    Fluorine (F) plays an important role in dental health and bone formation. Many studies have shown that excess fluoride (F−) can result in dental or skeletal fluorosis, while other studies have indicated that a proper dosage of fluoride may have a protective effect on bone fracture incidence. Fluorine is stored almost completely in the skeleton making bone an ideal site for measurement to assess long-term exposure. This paper outlines a feasibility study of a technique to measure bone-fluorine non-invasively in the human hand using in vivo neutron activation analysis (IVNAA) via the 19F(n,γ)20F reaction. Irradiations were performed using the Tandetron accelerator at McMaster University. Eight NaI(Tl) detectors arranged in a 4π geometry were employed for delayed counting of the emitted 1.63 MeV gamma ray. The short 11 s half-life of 20F presents a difficult and unique practical challenge in terms of patient irradiation and subsequent detection. We have employed two simultaneous timing methods to determine the fluorine sensitivity by eliminating the interference of the 1.64 MeV gamma ray from the 37Cl(n,γ)38Cl reaction. The timing method consisted of three counting periods: an initial 30 s (sum of three 10 s periods) count period for F, followed by a 120 s decay period, and a subsequent 300 s count period to obtain information pertaining to Ca and Cl. The phantom minimum detectable limit (MDL) determined by this method was 0.96 mg F/g Ca. The MDL was improved by dividing the initial timing period into three equal segments (10 s each) and combining the results using inverse variance weighting. This resulted in a phantom MDL of 0.66 mg F/g Ca. These detection limits are comparable to ex vivo results for various bones in the adult skeleton reported in the literature. Dosimetry was performed for these irradiation conditions. The equivalent dose for each phantom measurement was determined to be 30 mSv. The effective dose was however low, 35 µSv, which is comparable

  14. Osteoporosis: Peak Bone Mass in Women

    Science.gov (United States)

    ... Bone Health for Lupus Patients Bone Health and Anorexia Nervosa Partner Resources Screening Tests and Immunizations Guidelines for ... calcium. Physical Activity. Girls and boys and young adults who exercise regularly generally achieve greater peak bone ...

  15. Application of the active shape model in a commercial medical device for bone densitometry

    DEFF Research Database (Denmark)

    Thodberg, Hans Henrik; Rosholm, Anders

    2003-01-01

    sufficient list of initial guesses for the ASM. The performance of ASM and the experience with the integration of ASM in a commercial medical device is reported. The ASM achieves 99.5% reconstruction success and is able to validate its own reconstruction in 97% of the cases. The system (Pronosco X......Osteoporosis is a common disorder characterised mainly by low bone mineral density (BMD), and leading to an increased risk of fracture. We have developed a new device that estimates BMD from ordinary hand radiographs. A crucial element of this method is the reconstruction of the metacarpals. This...

  16. Bone sialoprotein does not interact with pro-gelatinase A (MMP-2 or mediate MMP-2 activation

    Directory of Open Access Journals (Sweden)

    McCulloch Christopher A

    2009-04-01

    Full Text Available Abstract Background A recent model for activation of the zymogen form of matrix metalloproteinase 2 (MMP-2, also known as gelatinase A has suggested that interactions between the SIBLING protein bone sialoprotein (BSP and MMP-2 leads to conformational change in MMP-2 that initiates the conversion of the pro-enzyme into a catalytically active form. This model is particularly relevant to cancer cell metastasis to bone since BSP, bound to the αvβ3 integrin through its arginine-glycine-aspartic acid motif, could recruit MMP-2 to the cell surface. Methods We critically assessed the relationship between BSP and proMMP-2 and its activation using various forms of recombinant and purified BSP and MMP-2. Gelatinase and collagenase assays, fluorescence binding assays, real-time PCR, cell culture and pull-down assays were employed to test the model. Results Studies with a fluorogenic substrate for MMP-2 showed no activation of proMMP-2 by BSP. Binding and pull-down assays demonstrated no interaction between MMP-2 and BSP. While BSP-mediated invasiveness has been shown to depend on its integrin-binding RGD sequence, analysis of proMMP-2 activation and the level of membrane type 1 (MT1-MMP in cells grown on a BSP substratum showed that the BSP-αvβ3 integrin interaction does not induce the expression of MT1-MMP. Conclusion These studies do not support a role for BSP in promoting metastasis through interactions with pro-MMP-2.

  17. Bone Cancer

    Science.gov (United States)

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

  18. Bone Cancer

    Science.gov (United States)

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

  19. Bone Diseases

    Science.gov (United States)

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

  20. Recombinant human bone morphogenetic protein induces bone formation

    International Nuclear Information System (INIS)

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

  1. Preimplant preparation of the extraction alveolus with the deproteinized bovine bone and calcium-sulphate

    Directory of Open Access Journals (Sweden)

    Brković Božidar

    2006-01-01

    Full Text Available Background. Different materials are used to prevent the resorption of alveolar bone. The aim of this report was to show the radiographical and histological results prior to implant insertion, when a deproteinized bovine bone mineral (BioOss and calcium-sulphate were placed into the extraction socket immediately after the tooth removal. Case report. A 22-year-old woman was scheduled for the removal of the second lower molar when the extraction socket was filled with BioOss covered with calcium-sulphate as a resorbable membrane. Primary closure of the surgical site was performed. Radiography was done 4 and 12 months later. One year after the surgery, when the implant was inserted, a biopsy of the new regenerated bone was obtained for the histological evaluation. The lamellar bone was evident using both materials. The resorption of BioOss was slow and the connective tissue was observed. Conclusion. Both materials had biocompatible and oseoconductive properties. One year after the grafting procedure, we observed the lamellar bone and partial resorption of BioOss, while calciumsulphate showed no significant effect as a resorbable membrane.

  2. Protocol for Bone Augmentation with Simultaneous Early Implant Placement: A Retrospective Multicenter Clinical Study

    Directory of Open Access Journals (Sweden)

    Peter Fairbairn

    2015-01-01

    Full Text Available Purpose. To present a novel protocol for alveolar bone regeneration in parallel to early implant placement. Methods. 497 patients in need of extraction and early implant placement with simultaneous bone augmentation were treated in a period of 10 years. In all patients the same specific method was followed and grafting was performed utilizing in situ hardening fully resorbable alloplastic grafting materials consisting of β-tricalcium phosphate and calcium sulfate. The protocol involved atraumatic extraction, implant placement after 4 weeks with simultaneous bone augmentation, and loading of the implant 12 weeks after placement and grafting. Follow-up periods ranged from 6 months to 10 years (mean of 4 years. Results. A total of 601 postextraction sites were rehabilitated in 497 patients utilizing the novel protocol. Three implants failed before loading and three implants failed one year after loading, leaving an overall survival rate of 99.0%. Conclusions. This standardized protocol allows successful long-term functional results regarding alveolar bone regeneration and implant rehabilitation. The concept of placing the implant 4 weeks after extraction, augmenting the bone around the implant utilizing fully resorbable, biomechanically stable, alloplastic materials, and loading the implant at 12 weeks seems to offer advantages when compared with traditional treatment modalities.

  3. The Ca, Cl, Mg, Na, and P mass fractions in benign and malignant giant cell tumors of bone investigated by neutron activation analysis

    International Nuclear Information System (INIS)

    The Ca, Cl, Mg, Na, and P content and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na ratios in samples of intact bone, benign and malignant giant cell tumor (GCT) of bone were investigated by neutron activation analysis with high resolution spectrometry of short-lived radionuclides. It was found that in GCT tissue the mass fractions of Cl and Na are higher and the mass fraction of Ca and P are lower than in normal bone tissues. Moreover, it was shown that higher Cl/Na mass fraction ratios as well as lower Ca/Cl, Ca/Mg, and Ca/Na mass fraction ratios are typical of the GCT tissue compared to intact bone. Finally, we propose to use the estimation of such parameters as the Cl mass fraction and the Ca/Cl mass fraction ratio as an additional test for differential diagnosis between benign and malignant GCT. (author)

  4. The diphosphonate space: A useful quantitative index of disease activity in patients undergoing hexamethylene diphosphonate (HMDP) bone imaging for Paget's disease

    International Nuclear Information System (INIS)

    Comparison between the plasma levels of intravenously injected technetium 99m hexamethylene diphosphonate (99mTc-HMDP) and chromium 151 ethylenediaminetetraacetic acid (51Cr-EDTA) reflects the uptake of diphosphonate into bone (the diphosphonate space). This can be used as an index of skeletal function in metabolic bone disease. In a series of 49 patients with Paget's disease the diphosphonate space (DPS) correlated well with other indicators of disease activity such as alkaline phosphatase and urinary hydroxyproline levels. The DPS is a good predictor of the volume of skeletal involvement as estimated from bone images. The DPS also provides a sensitive indicator of response to treatment with intravenously administered bisphosphonate. The DPS is simple to perform and is a useful adjunct to routine bone imaging. (orig.)

  5. Scoring of synovial membrane hypertrophy and bone erosions by MR imaging in clinically active and inactive rheumatoid arthritis of the wrist

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Gideon, P; Sørensen, K;

    1995-01-01

    MRI-scores of synovial membrane hypertrophy and bone erosions of the RA-wrist are introduced. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) and conventional radiography (CR) of the wrist were performed in 16 patients with rheumatoid arthritis (RA) and 3 healthy controls. A MRI-score of...... MRI and CR with respect to bone erosions. Bone erosions were detected by MRI in 14 wrists in contrast to only 6 wrists by CR. In all patients the erosions were more numerous on MRI. The introduced methods may be useful quantitative measures of synovitis and early joint destruction in RA....... synovial membrane hypertrophy was obtained by summation of gradings of synovial hypertrophy in 6 regions of the wrist. The score was significantly higher in wrists with than in wrists without clinical signs of active arthritis. The score was 0 in all healthy controls. Each bone of the wrist was assessed by...

  6. Tissue reactions to particles of bone-substitute materials in intraosseous and heterotopic sites in rats: discrimination of osteoinduction, osteocompatibility, and inflammation.

    Science.gov (United States)

    Eid, K; Zelicof, S; Perona, B P; Sledge, C B; Glowacki, J

    2001-09-01

    Two rat models were used to characterize tissue-specific reactions to particles of bone-substitute materials: one for osteocompatibility in a healing tibial wound and the other in a heterotopic, subcutaneous site. Small, unicortical tibial wounds in rats healed spontaneously, beginning with the rapid proliferation of intramedullary woven bone. That temporary bone was resorbed by osteoclasts and finally, the cortical wound was healed with lamellar bone and the medullary space was repopulated with marrow. When various particulate materials were implanted into fresh wounds, three types of reactions were observed. (1) Demineralized bone powder (DBP) and non-resorbable calcium phosphate (nrCP) were incorporated into the reactive medullary and cortical bone. (2) Polymethylmetlhacrylate (PMMA) particles were surrounded with a fibrous layer, but did not impair bone healing. (3) Polyethylene (PE) shards and resorbable calcium phosphates (rCPs) were inflammatory and inhibited osseous repair. Subcutaneous sites showed osteoinductive, fibrotic, or inflammatory responses to these materials. Only DBP induced endochondral osteogenesis subcutaneously. The nrCP evoked a fibrous reaction. In contrast, rCPs, PMMA, and PE shards generated inflammatory reactions with each particle being surrounded by fibrous tissue and large multinucleated giant cells. In conclusion, only DBP showed osteoinductive as well as osteocompatible properties. The nrCP was osteocompatible. The rCPs stimulated various degrees of inflammatory responses. PMMA was osteocompatible and did not interfere with the bone healing process. PE was not osteocompatible and generated foreign body reactions in both sites. Use of the two sites distinguishes osteoinductive, osteocompatible, and inflammatory properties of particles of bone-substitute materials. PMID:11562148

  7. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  8. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

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

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina;

    2004-01-01

    Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone form...

  10. Microgravity induces pelvic bone loss through osteoclastic activity, osteocytic osteolysis, and osteoblastic cell cycle inhibition by CDKN1a/p21.

    Science.gov (United States)

    Blaber, Elizabeth A; Dvorochkin, Natalya; Lee, Chialing; Alwood, Joshua S; Yousuf, Rukhsana; Pianetta, Piero; Globus, Ruth K; Burns, Brendan P; Almeida, Eduardo A C

    2013-01-01

    Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arrest during osteogenesis may also contribute to bone loss in space. To test this possibility, we exposed 16-week-old female C57BL/6J mice (n = 8) to microgravity for 15-days on the STS-131 space shuttle mission. Analysis of the pelvis by µCT shows decreases in bone volume fraction (BV/TV) of 6.29%, and bone thickness of 11.91%. TRAP-positive osteoclast-covered trabecular bone surfaces also increased in microgravity by 170% (p = 0.004), indicating osteoclastic bone degeneration. High-resolution X-ray nanoCT studies revealed signs of lacunar osteolysis, including increases in cross-sectional area (+17%, p = 0.022), perimeter (+14%, p = 0.008), and canalicular diameter (+6%, p = 0.037). Expression of matrix metalloproteinases (MMP) 1, 3, and 10 in bone, as measured by RT-qPCR, was also up-regulated in microgravity (+12.94, +2.98 and +16.85 fold respectively, p<0.01), with MMP10 localized to osteocytes, and consistent with induction of osteocytic osteolysis. Furthermore, expression of CDKN1a/p21 in bone increased 3.31 fold (p<0.01), and was localized to osteoblasts, possibly inhibiting the cell cycle during tissue regeneration as well as conferring apoptosis resistance to these cells. Finally the apoptosis inducer Trp53 was down-regulated by -1.54 fold (p<0.01), possibly associated with the quiescent survival-promoting function of CDKN1a/p21. In conclusion, our findings identify the pelvic and femoral region of the mouse skeleton as an active site of rapid bone

  11. Non-viral gene activated matrices for mesenchymal stem cells based tissue engineering of bone and cartilage.

    Science.gov (United States)

    Raisin, Sophie; Belamie, Emmanuel; Morille, Marie

    2016-10-01

    Recent regenerative medicine and tissue engineering strategies for bone and cartilage repair have led to fascinating progress of translation from basic research to clinical applications. In this context, the use of gene therapy is increasingly being considered as an important therapeutic modality and regenerative technique. Indeed, in the last 20 years, nucleic acids (plasmid DNA, interferent RNA) have emerged as credible alternative or complement to proteins, which exhibited major issues including short half-life, loss of bioactivity in pathologic environment leading to high dose requirement and therefore high production costs. The relevance of gene therapy strategies in combination with a scaffold, following a so-called "Gene-Activated Matrix (GAM)" approach, is to achieve a direct, local and sustained delivery of nucleic acids from a scaffold to ensure efficient and durable cell transfection. Among interesting cells sources, Mesenchymal Stem Cells (MSC) are promising for a rational use in gene/cell therapy with more than 1700 clinical trials approved during the last decade. The aim of the present review article is to provide a comprehensive overview of recent and ongoing work in non-viral genetic engineering of MSC combined with scaffolds. More specifically, we will show how this inductive strategy can be applied to orient stem cells fate for bone and cartilage repair. PMID:27467418

  12. Preparation and Characterization of Activated Cow Bone Powder for the Adsorption of Cadmium from Palm Oil Mill Effluent

    Science.gov (United States)

    AbdulRahman, A.; Latiff, A. A. A.; Daud, Z.; Ridzuan, M. B.; D, N. F. M.; Jagaba, A. H.

    2016-07-01

    Several studies have been conducted on the removal of heavy metals from palm oil mill effluent. In this study, cow bones were developed as an adsorbent for the removal of cadmium II from POME. A batch experiment was conducted to investigate the effectiveness of the prepared activated cow bone powder for the sorption of cadmium II from raw POME. The experiment was carried out under fixed conditions using 100mg/L raw POME combined with different adsorbent dosage of CBP of 184.471 Ra(nm) surface roughness. The equilibrium adsorption capacity of the hydrophobic CBP of average contact angle 890 was determined from the relationship between the initial and equilibrium liquid phase concentrations of POME. The optimum adsorption of cadmium II on CBP was at 10g adsorbent dosage for sample 1 and 2 at 97.8% and 96.93% respectively. The least uptake was at 30g adsorbent weight for both samples at average of 95.1% for both samples. The effective removal of cadmium ion showed that CBP has a great potential for the treatment of heavy metal in POME.

  13. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  14. Severely Resorbed Edentulous Ridges: A Preventive Prosthodontic Approach - A Case Report.

    Science.gov (United States)

    Karnam, Shalini; Basimi, Swapna; Surapaneni, Haragopal; Basapogu, Sreeramulu; Gantala, Ramlal

    2015-10-01

    As a dentist our main aim should be prevention which not only includes prevention of caries and or periodontal disease but also prevention of residual alveolar bone loss after teeth are extracted. Today with greater stress on preventive measures, the dental profession has expanded this preventive concept into Prosthodontics. Preventive Prosthodontics emphasizes the importance of any procedure that can delay or eliminate the future Prosthodontic problem and stop further progression of oral disease and prevent the loss of remaining tissues. The Residual Ridge Resorption (RRR) is an inevitable consequence of tooth loss and denture wearing. Severe RRR gradually results in increased interarch distance, significant horizontal discrepancy between edentulous ridges, occurrence of flabby displaceable tissues in the denture bearing area and other sequelae. Prosthetic rehabilitation in these patients can be challenging. The conventional complete denture fabrication in such cases may further compound the poor denture bearing ability of the tissues and lead to decreased retention, stability and support which may result in psychological problems and social isolation. This case report emphasizes the importance of preventive concepts in every step of complete denture fabrication to offer a long serviceable prosthesis without any significant complications and compromise. PMID:26557629

  15. A prosthodontic management of severely resorbed anterior ridge defect - a case report.

    Science.gov (United States)

    Rai, Rathika; V, Menaga; R, Prabhu; Kr, Geetha; R, Suprabha

    2014-09-01

    The Dental profession has devoted most of its history to restoring the effects of dental disease. The public's interest in Dental health and beauty has become an engine that continues to drive the demand for cosmetic dental procedures. In the past, achieving a beautiful smile required submission to extensive invasive procedures and expensive fixed dental prosthetic restorations. Advancements in restorative material formulations and adhesive technology have expanded such possibilities. Despite many recent advances in aesthetic dentistry techniques and materials, certain cases remain difficult to restore. Replacing missing anterior teeth presents a serious challenge to the clinicians especially with a large ridge defect. Such cases require not only replacement of the missing teeth but also the restoration of the bone defect, aesthetics and phonetics. While the conventional treatment approaches like fixed partial denture or an option of implant may not justify the restoration of the defects. A combination of fixed and removable restoration provides good alternative. The aim and purpose of this case report is to describe a multidisciplinary approach of managing a patient who reported with a similar complaint of missing anterior teeth with anterior ridge defect hoping to get not only her teeth but also her lost smile. PMID:25386538

  16. Gene-Activated Matrix Comprised of Atelocollagen and Plasmid DNA Encoding BMP4 or Runx2 Promotes Rat Cranial Bone Augmentation.

    Science.gov (United States)

    Umebayashi, Mayumi; Sumita, Yoshinori; Kawai, Yousuke; Watanabe, Sumiko; Asahina, Izumi

    2015-01-01

    To date, therapeutic method for in vivo gene delivery has not been established on bone engineering though its potential usefulness has been suggested. For clinical applications, an effective condition should be developed to transfer the genes in vivo without any transfection reagents or virus vectors. In this study, to facilitate the clinical setting of this strategy, particularly aimed at atrophic bone repair, we simply investigated whether manufactured gene-activated matrix (GAM) with atelocollagen containing a certain amount of plasmid (p) DNA encoding osteogenic proteins could augment the cranial bone in rat. GAMs were manufactured by mixing 0.02, 0.1, or 1 mg of AcGFP plasmid vectors harboring cDNA of BMP4 (pBMP4) or Runx2 (pRunx2) with 2% bovine atelocollagen and β-tricalcium phosphate granules. Before manufacturing GAMs, to determine the biological activity of generated pDNAs, we confirmed GFP expression and increased level of alkaline phosphatase activities in MC3T3-E1 cells transfected with pBMP4 or pRunx2 during culture. Then, GAMs were lyophilized and transplanted to onlay placement on the cranium. At 2 weeks of transplantation, GFP-expressing cells could be detectable in only GAMs containing 1 mg of AcGFP plasmid vectors. Then, at 4 weeks, significant bone formation was recognized in GAMs containing 1 mg of pDNAs encoding BMP4 or Runx2 but not in 0.02 or 0.1 mg of GAMs. These newly formed bone tissues surrounded by osteocalcin-stained area were augmented markedly until 8 weeks after transplantation. In contrast, minimal bone formation was observed in GAMs without harboring cDNA of osteogenic proteins. Meanwhile, when GAMs were transplanted to the cranial bone defect, bone formation was detectable in specimens containing 1 mg of pBMP4 or pRunx2 at 8 weeks as well. Thus, atelocollagen-based GAM reliably could form the engineered bone even for the vertical augmentation when containing a certain amount of plasmid vectors encoding osteogenic

  17. Electrospun Gelatin/β-TCP Composite Nanofibers Enhance Osteogenic Differentiation of BMSCs and In Vivo Bone Formation by Activating Ca2+-Sensing Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Xuehui Zhang

    2015-01-01

    Full Text Available Calcium phosphate- (CaP- based composite scaffolds have been used extensively for the bone regeneration in bone tissue engineering. Previously, we developed a biomimetic composite nanofibrous membrane of gelatin/β-tricalcium phosphate (TCP and confirmed their biological activity in vitro and bone regeneration in vivo. However, how these composite nanofibers promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs is unknown. Here, gelatin/β-TCP composite nanofibers were fabricated by incorporating 20 wt% β-TCP nanoparticles into electrospun gelatin nanofibers. Electron microscopy showed that the composite β-TCP nanofibers had a nonwoven structure with a porous network and a rough surface. Spectral analyses confirmed the presence and chemical stability of the β-TCP and gelatin components. Compared with pure gelatin nanofibers, gelatin/β-TCP composite nanofibers caused increased cell attachment, proliferation, alkaline phosphatase activity, and osteogenic gene expression in rat BMSCs. Interestingly, the expression level of the calcium-sensing receptor (CaSR was significantly higher on the composite nanofibrous scaffolds than on pure gelatin. For rat calvarial critical sized defects, more extensive osteogenesis and neovascularization occurred in the composite scaffolds group compared with the gelatin group. Thus, gelatin/β-TCP composite scaffolds promote osteogenic differentiation of BMSCs in vitro and bone regeneration in vivo by activating Ca2+-sensing receptor signaling.

  18. Mimicking the nanostructure of bone matrix to regenerate bone.

    Science.gov (United States)

    Kane, Robert; Ma1, Peter X

    2013-11-01

    Key features of bone tissue structure and composition are capable of directing cellular behavior towards the generation of new bone tissue. Bone tissue, as well as materials derived from bone, have a long and successful history of use as bone grafting materials. Recent developments in design and processing of synthetic scaffolding systems has allowed the replication of the bone's desirable biological activity in easy to fabricate polymeric materials with nano-scale features exposed on the surface. The biological response to these new tissue-engineering scaffold materials oftentimes exceeds that seen on scaffolds produced using biological materials. PMID:24688283

  19. Bone morphogenetic protein 2-induced human dental pulp cell differentiation involves p38 mitogen-activated protein kinase-activated canonical WNT pathway

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Ling Ye; Tian-Qian Hui; Dong-Mei Yang; Ding-Ming Huang; Xue-Dong Zhou; Jeremy J Mao; Cheng-Lin Wang

    2015-01-01

    Both bone morphogenetic protein 2 (BMP2) and the wingless-type MMTV integration site (WNT)/b-catenin signalling pathway play important roles in odontoblast differentiation and dentinogenesis. Cross-talk between BMP2 and WNT/b-catenin in osteoblast differentiation and bone formation has been identified. However, the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely unknown. Here, we demonstrate that BMP2 promotes the differentiation of human dental pulp cells (HDPCs) by activating WNT/b-catenin signalling, which is further mediated by p38 mitogen-activated protein kinase (MAPK) in vitro. BMP2 stimulation upregulated the expression of b-catenin in HDPCs, which was abolished by SB203580 but not by Noggin or LDN193189. Furthermore, BMP2 enhanced cell differentiation, which was not fully inhibited by Noggin or LDN193189. Instead, SB203580 partially blocked BMP2-induced b-catenin expression and cell differentiation. Taken together, these data suggest a possible mechanism by which the elevation of b-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway, which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.

  20. Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease

    DEFF Research Database (Denmark)

    Onuma, Yoshinobu; Dudek, Dariusz; Thuesen, Leif; Webster, Mark; Nieman, Koen; Garcia-Garcia, Hector M; Ormiston, John A; Serruys, Patrick W

    2013-01-01

    This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California).......This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California)....

  1. Bone marrow stromal cells from multiple myeloma patients uniquely induce bortezomib resistant NF-κB activity in myeloma cells

    Directory of Open Access Journals (Sweden)

    Kim KyungMann

    2010-07-01

    Full Text Available Abstract Background Components of the microenvironment such as bone marrow stromal cells (BMSCs are well known to support multiple myeloma (MM disease progression and resistance to chemotherapy including the proteasome inhibitor bortezomib. However, functional distinctions between BMSCs in MM patients and those in disease-free marrow are not completely understood. We and other investigators have recently reported that NF-κB activity in primary MM cells is largely resistant to the proteasome inhibitor bortezomib, and that further enhancement of NF-κB by BMSCs is similarly resistant to bortezomib and may mediate resistance to this therapy. The mediating factor(s of this bortezomib-resistant NF-κB activity is induced by BMSCs is not currently understood. Results Here we report that BMSCs specifically derived from MM patients are capable of further activating bortezomib-resistant NF-κB activity in MM cells. This induced activity is mediated by soluble proteinaceous factors secreted by MM BMSCs. Among the multiple factors evaluated, interleukin-8 was secreted by BMSCs from MM patients at significantly higher levels compared to those from non-MM sources, and we found that IL-8 contributes to BMSC-induced NF-κB activity. Conclusions BMSCs from MM patients uniquely enhance constitutive NF-κB activity in MM cells via a proteinaceous secreted factor in part in conjunction with IL-8. Since NF-κB is known to potentiate MM cell survival and confer resistance to drugs including bortezomib, further identification of the NF-κB activating factors produced specifically by MM-derived BMSCs may provide a novel biomarker and/or drug target for the treatment of this commonly fatal disease.

  2. Soy isoflavones do not affect bone resorption in postmenopausal women: A dose-response study using a novel approach with Ca-41

    OpenAIRE

    Cheong, J. M. K.; Martin, B R; Jackson, G.S.; Elmore, D.; McCabe, G. P.; Nolan, J R; Barnes, S.; Peacock, M.; Weaver, C. M.

    2007-01-01

    Introduction: The purpose of this 3-way crossover study was to identify the effective dose of soy protein isolate enriched with isoflavones for suppressing bone resorption in postmenopausal women using a novel, rapid assessment of antibone resorbing treatments. Methods: Thirteen postmenopausal women (>= 6 yr since menopause) were predosed with Ca-41 iv. After a 200-d baseline period, subjects were given 43 g soy p...

  3. From Tootsie Rolls to Broken Bones: An Innovative Approach for Active Learning in Mechanics of Materials

    Science.gov (United States)

    Linsey, Julie; Talley, Austin; White, Christina; Jensen, Dan; Wood, Kristin

    2009-01-01

    Active learning enhances engineering education. This paper presents rationale, curriculum supplements, and an approach to active learning that may be seamlessly incorporated into a traditional lecture-based engineering class. A framework of educational theory that structures the active learning experiences and includes consideration of learning…

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

    Science.gov (United States)

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

    2007-05-01

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

  5. Resorbable composites with bioresorbable glass fibers for load-bearing applications. In vitro degradation and degradation mechanism.

    Science.gov (United States)

    Lehtonen, Timo J; Tuominen, Jukka U; Hiekkanen, Elina

    2013-01-01

    An in vitro degradation study of three bioresorbable glass fiber-reinforced poly(l-lactide-co-dl-lactide) (PLDLA) composites was carried out in simulated body fluid (SBF), to simulate body conditions, and deionized water, to evaluate the nature of the degradation products. The changes in mechanical and chemical properties were systematically characterized over 52 weeks dissolution time to determine the degradation mechanism and investigate strength retention by the bioresorbable glass fiber-reinforced PLDLA composite. The degradation mechanism was found to be a combination of surface and bulk erosion and does not follow the typical core-accelerated degradation mechanism of poly(α-hydroxyacids). Strength retention by bioresorbable glass fiber-reinforced PLDLA composites can be tailored by changing the oxide composition of the glass fibers, but the structure-property relationship of the glass fibers has to be understood and controlled so that the phenomenon of ion leaching can be utilized to control the degradation rate. Therefore, these high performance composites are likely to open up several new possibilities for utilizing resorbable materials in clinical applications which could not be realized in the past. PMID:22963847

  6. Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

    Science.gov (United States)

    Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

    1997-05-01

    The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

  7. Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity

    International Nuclear Information System (INIS)

    Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is known to cause bone toxicity, particularly during animal development, although its action mechanism to cause this toxicity has yet to be elucidated. Mouse pups were exposed to TCDD via dam's milk that were administered orally with 15 μg TCDD/kg b.w. on postnatal day 1. Here we report that TCDD causes up-regulation of vitamin D 1α-hydroxylase in kidney, resulting in a 2-fold increase in the active form of vitamin D, 1,25-dihydroxyvitamin D3, in serum. This action of TCDD is not caused by changes in parathyroid hormone, a decrease in vitamin D degrading enzyme, vitamin D 24-hydroxylase, or alterations in serum Ca2+ concentration. Vitamin D is known to affect bone mineralization. Our data clearly show that TCDD-exposed mice exhibit a marked decrease in osteocalcin and collagen type 1 as well as alkaline phosphatase gene expression in tibia by postnatal day 21, which is accompanied with a mineralization defect in the tibia, lowered activity of osteoblastic bone formation, and an increase in fibroblastic growth factor-23, a sign of increased vitamin D effect. Despite these significant effects of TCDD on osteoblast activities, none of the markers of osteoclast activities was found to be affected. Histomorphometry confirmed that osteoblastic activity, but not bone resorption activity, was altered by TCDD. A prominent lesion commonly observed in these TCDD-treated mice was impaired bone mineralization that is characterized by an increased volume and thickness of osteoids lining both the endosteum of the cortical bone and trabeculae. Together, these data suggest that the impaired mineralization resulting from reduction of the osteoblastic activity, which is caused by TCDD-induced up-regulation of vitamin D, is responsible for its bone developmental toxicity.

  8. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo

    OpenAIRE

    Yunhao Qin; Lian Wang; Zhengliang Gao; Genyin Chen; Changqing Zhang

    2016-01-01

    Emerging evidence suggests that extracellular vesicles (EVs) are secreted by diverse tissues and play important roles in cell-cell communication, organ interactions and tissue homeostasis. Studies have reported the use of EVs to stimulate tissue regeneration, such as hepatic cell regeneration, and to treat diseases, such as pulmonary hypertension. However, little is known about the osteogenic effect of EVs. In this study, we explore the role of bone marrow stromal cell-derived EVs in the regu...

  9. Transcriptional Link between Blood and Bone: the Stem Cell Leukemia Gene and Its +19 Stem Cell Enhancer Are Active in Bone Cells

    OpenAIRE

    Pimanda, John E; Silberstein, Lev; Dominici, Massimo; Dekel, Benjamin; Bowen, Mark; Oldham, Scott; Kallianpur, Asha; Brandt, Stephen J.; Tannahill, David; Göttgens, Berthold; Green, Anthony R.

    2006-01-01

    Blood and vascular cells are generated during early embryogenesis from a common precursor, the hemangioblast. The stem cell leukemia gene (SCL/tal 1) encodes a basic helix-loop-helix transcription factor that is essential for the normal development of blood progenitors and blood vessels. We have previously characterized a panel of SCL enhancers including the +19 element, which directs expression to hematopoietic stem cells and endothelium. Here we demonstrate that SCL is expressed in bone pri...

  10. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

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

    Science.gov (United States)

    Rodionova, Natalia; Kabitskaya, Olga

    2016-07-01

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

  12. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  13. The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats.

    Science.gov (United States)

    Takizawa, Aiko; Chiba, Mirei; Ota, Takeru; Yasuda, Mayumi; Suzuki, Keiko; Kanemitsu, Takuya; Itoh, Takashi; Shinoda, Hisashi; Igarashi, Kaoru

    2016-05-01

    The novel bisphosphonate (BP) disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. We investigated the systemic effects of this compound on bone loss induced by ovariectomy (OVX) in adult rats. Micro-computed tomography revealed that MPMBP increased bone mass and density in both the metaphysis and diaphysis, and improved the structural properties important for mechanical strength of osteoporotic bone. Sequential bone labeling with tetracycline and calcein indicated that MPMBP decreased longitudinal growth of the primary spongiosa (PS), but stimulated cortical bone formation in the diaphysis. MPMBP increased type I collagen accumulation in the PS, and decreased the number and size of adipocytes in the bone marrow, suggesting inhibition of increased bone marrow adipogenesis induced by OVX. Furthermore, MPMBP reduced the number of bone resorbing cathepsin K-positive osteoclasts induced by OVX. These results suggest that MPMBP could improve bone loss induced by estrogen deficiency. Both stimulation of bone formation and inhibition of bone resorption might play a role in the increase in bone mass and bone density after MPMBP treatment. PMID:27245552

  14. Locomotor activity influences muscle architecture and bone growth but not muscle attachment site morphology

    OpenAIRE

    Rabey, Karyne N.; Green, David J; Taylor, Andrea B.; Begun, David R.; Richmond, Brian G.; McFarlin, Shannon C.

    2014-01-01

    The ability to make behavioural inferences from skeletal remains is critical to understanding the lifestyles and activities of past human populations and extinct animals. Muscle attachment site (enthesis) morphology has long been assumed to reflect muscle strength and activity during life, but little experimental evidence exists to directly link activity patterns with muscle development and the morphology of their attachments to the skeleton. We used a mouse model to experimentally test how t...

  15. Playing with bone and fat

    DEFF Research Database (Denmark)

    Gimble, Jeffrey M.; Zvonic, Sanjin; Floyd, Z. Elisabeth;

    2006-01-01

    The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or...

  16. Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types

    Directory of Open Access Journals (Sweden)

    Dijkstra Christine D

    2011-05-01

    Full Text Available Abstract Background Macrophages play an important role in neuroinflammatory diseases such as multiple sclerosis (MS and spinal cord injury (SCI, being involved in both damage and repair. The divergent effects of macrophages might be explained by their different activation status: classically activated (CA/M1, pro-inflammatory, macrophages and alternatively activated (AA/M2, growth promoting, macrophages. Little is known about the effect of macrophages with these phenotypes in the central nervous system (CNS and how they influence pathogenesis. The aim of this study was therefore to determine the characteristics of these phenotypically different macrophages in the context of the CNS in an in vitro setting. Results Here we show that bone marrow derived CA and AA macrophages have a distinct migratory capacity towards medium conditioned by various cell types of the CNS. AA macrophages were preferentially attracted by the low weight ( Conclusion In conclusion, since AA macrophages are more motile and are attracted by NCM, they are prone to migrate towards neurons in the CNS. CA macrophages have a lower motility and a stronger adhesion to ECM. In neuroinflammatory diseases the restricted migration and motility of CA macrophages might limit lesion size due to bystander damage.

  17. The influence of thyroid function and bone turnover on lipoprotein profile in young physically active men with different insulin sensitivity.

    Science.gov (United States)

    Kęska, A; Lutosławska, G; Czajkowska, A; Tkaczyk, J; Mazurek, K; Tomaszewski, P

    2014-06-01

    Physical activity induces changes in the endocrine system. Previous data indicated that changes in insulin secretion and the tissue response to this hormone are very important for energy metabolism. It is believed that they are accompanied by changes in lipid metabolism, but factors contributing to this process are still disputed. The aim of this study was to assess interactions among insulin sensitivity, thyroid function, a bone turnover marker and serum lipid profile in young physically active men. Eighty-seven physical education students, aged 18-23 years, participated in the study. We measured serum levels of glucose, lipids, insulin, thyroid-stimulating hormone (TSH), osteocalcin and anthropometric parameters. Insulin sensitivity was determined using homeostatic model assessment for insulin resistance (HOMA-IR). The median value of HOMA-IR (1.344) was used to divide the study population into Group A (above the median) and Group B (below the median). Men from both groups did not differ in anthropometric parameters or in daily physical activity. Triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were higher in Group A (P lipid profile at a certain level of insulin sensitivity. PMID:24899778

  18. The changes of cardioelectrical activity of rat with myocardial infarction receiving sarcoplasmic reticulum Ca2+-ATPase gene modified bone marrow stem cell transplantation by microelectrode array technology

    Institute of Scientific and Technical Information of China (English)

    范平

    2012-01-01

    Objective Therapy effects and cardiac electrical activity comparison of bone marrow stem cells (BMSCs) transplantation and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) gene modified BMSCs transplantation after acute myocardial infarction(AMI) in rats.Methods Rats with AMI were divided

  19. Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

    Energy Technology Data Exchange (ETDEWEB)

    Ma, W.H.; Liu, Y.J.; Wang, W.; Zhang, Y.Z. [The Third Hospital of Hebei Medical University, The Provincial Key Laboratory for Orthopedic Biomechanics of Hebei, Shijiazhuang, Hebei Province (China)

    2015-02-13

    Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

  20. Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

    International Nuclear Information System (INIS)

    Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation

  1. Skeletal changes in osteoprotegerin and receptor activator of nuclear factor-kappab ligand mRNA levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism

    DEFF Research Database (Denmark)

    Stilgren, L S; Rettmer, E; Eriksen, E F;

    2004-01-01

    The effect of parathyroid hormone (PTH) on the production of osteoprotegerin (OPG) and ligand of receptor activator of NF-kappaB (RANKL) in human bone is incompletely understood. Most in vitro studies indicate that PTH decreases OPG and increases RANKL production. In primary hyperparathyroidism (...

  2. Bone health in eating disorders.

    Science.gov (United States)

    Zuckerman-Levin, N; Hochberg, Z; Latzer, Y

    2014-03-01

    Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health. Low bone mineral density (BMD) with ED is caused by failure to accrue peak bone mass in adolescence and bone loss in young adulthood. Although ED patients diagnosed with bone loss may be asymptomatic, some suffer bone pains and have increased incidence of fractures. Adolescents with ED are prone to increased prevalence of stress fractures, kyphoscoliosis and height loss. The clinical picture of the various EDs involves endocrinopathies that contribute to impaired bone health. Anorexia nervosa (AN) is characterized by low bone turnover, with relatively higher osteoclastic (bone resorptive) than osteoblastic (bone formation) activity. Bone loss in AN occurs in both the trabecular and cortical bones, although the former is more vulnerable. Bone loss in AN has been shown to be influenced by malnutrition and low weight, reduced fat mass, oestrogen and androgen deficiency, glucocorticoid excess, impaired growth hormone-insulin-like growth factor 1 axis, and more. Bone loss in AN may not be completely reversible despite recovery from the illness. Treatment modalities involving hormonal therapies have limited effectiveness, whereas increased caloric intake, weight gain and resumption of menses are essential to improved BMD. PMID:24165231

  3. Low Bone Density

    Science.gov (United States)

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

  4. Development of a transportable neutron activation analysis system to quantify manganese in bone in vivo: feasibility and methodology

    International Nuclear Information System (INIS)

    This study was conducted to investigate the methodology and feasibility of developing a transportable neutron activation analysis (NAA) system to quantify manganese (Mn) in bone using a portable deuterium–deuterium (DD) neutron generator as the neutron source. Since a DD neutron generator was not available in our laboratory, a deuterium–tritium (DT) neutron generator was used to obtain experimental data and validate the results from Monte Carlo (MC) simulations. After validation, MC simulations using a DD generator as the neutron source were then conducted. Different types of moderators and reflectors were simulated, and the optimal thicknesses for the moderator and reflector were determined. To estimate the detection limit (DL) of the system, and to observe the interference of the magnesium (Mg) γ line at 844 keV to the Mn γ line at 847 keV, three hand phantoms with Mn concentrations of 30 parts per million (ppm), 150 ppm, and 500 ppm were made and irradiated by the DT generator system. The Mn signals in these phantoms were then measured using a 50% high-efficiency high-purity germanium (HPGe) detector. The DL was calculated to be about 4.4 ppm for the chosen irradiation, decay, and measurement time. This was calculated to be equivalent to a DL of about 3.3 ppm for the DD generator system. To achieve this DL with one 50% high-efficiency HPGe detector, the dose to the hand was simulated to be about 37 mSv, with the total body equivalent dose being about 23µSv. In conclusion, it is feasible to develop a transportable NAA system to quantify Mn in bone in vivo with an acceptable radiation exposure to the subject. (paper)

  5. Bone scanning in osteoporosis

    International Nuclear Information System (INIS)

    This paper reports on bone scanning in osteoporosis a diagnosis of osteoporosis most often follows fracture, and clearly this should be confirmed by x-ray. The bone scan therefore does not have an important role to play in the initial diagnosis of osteoporosis. While the exact mechanism by which the 99mTc-labeled diphosphonates localize in the skeleton is not fully understood, it is believed that they adsorb onto bone surfaces most probably via the calcium of hydroxyapatite crystals. Because the major factors that affect adsorption are osteoblastic activity and to a lesser extent skeletal vascularity, it is apparent that a bone scan image presents a functional display of skeletal metabolic activity. However, osteoporosis is a disorder in which gradual change in bone mass may occur over many years and, in keeping with this minor imbalance in skeletal metabolism, the bone scan appearances are usually normal. However, the scan images may appear of poor quality because of relatively low bone uptake of tracer with, on occasion, a washed-out pattern of activity in the axial and appendicular bone. It has been suggested that such a pattern occurs in severe or end-stage osteoporosis caused by markedly reduced osteoblastic activity. If kyphosis is observed on the bone scan or if there appears to be loss of spinal height with proximity of ribs to each other or increased closeness of rib cage to pelvis, then appearances suggest vertebral collapse and would be in keeping with a diagnosis of osteoporosis. Such evidence is, however, indirect and in practice a bone scan is an extremely unreliable means of diagnosing osteoporosis

  6. The study of in vivo quantification of aluminum (Al) in human bone with a compact DD generator-based neutron activation analysis (NAA) system.

    Science.gov (United States)

    Byrne, Patrick; Mostafaei, Farshad; Liu, Yingzi; Blake, Scott P; Koltick, David; Nie, Linda H

    2016-05-01

    The feasibility and methodology of using a compact DD generator-based neutron activation analysis system to measure aluminum in hand bone has been investigated. Monte Carlo simulations were used to simulate the moderator, reflector, and shielding assembly and to estimate the radiation dose. A high purity germanium (HPGe) detector was used to detect the Al gamma ray signals. The minimum detectable limit (MDL) was found to be 11.13 μg g(-1) dry bone (ppm). An additional HPGe detector would improve the MDL by a factor of 1.4, to 7.9 ppm. The equivalent dose delivered to the irradiated hand was calculated by Monte Carlo to be 11.9 mSv. In vivo bone aluminum measurement with the DD generator was found to be feasible among general population with an acceptable dose to the subject. PMID:27093035

  7. Trace elements determination in human bone tissue by neutron activation analysis; Determinacao de elementos de traco em tecido osseo humano pelo metodo de ativacao com neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Takata, Marcelo K.; Saiki, Mitiko [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Div. de Radioquimica; Sumita, Nairo M.; Saldiva, Paulo H.N.; Pasqualucci, Carlos A. [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Lab. Experimental de Poluicao Atmosferica

    2002-07-01

    Determination of trace elements in human bones is of the great interest for evaluating nutritional state and for prevention, control and study of several diseases caused by mineral or trace element imbalance. In this study, neutron activation analysis (NAA) was applied for trace elements in human rib bone tissue. Elements Ba, Br, Ca, Cl, Fe, K, Mg, Mn, Na, P, Rb, Sr and Zn were determined in total bone tissue and in its subcompartments (cortical and trabecular tissue) separately. Irradiations were performed at IEA-R1 nuclear research reactor of IPEN-CNEN/SP. Short irradiations of 4 minutes were carried out under thermal neutron flux of 4.5x10{sup 11} n cm{sup -2} s{sup -1} and long irradiations of 16 hours under neutron flux of 10{sup 12} n cm{sup -2} s{sup -1}. Results obtained showed a variability between elemental concentrations found for bones from different individuals. A comparative study made between the data obtained for cortical and trabecular bones indicated that these two tissues present different elemental concentrations. Concentrations of Ca, Mg, Na and P obtained for cortical tissue were the same magnitude of those published data. (author)

  8. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli

    Science.gov (United States)

    Rubin, C.; Xu, G.; Judex, S.

    2001-01-01

    It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that extremely low-magnitude (<10 microstrain) mechanical signals readily stimulate bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control (+97%). Disuse alone reduced BFR (-92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing (-61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.

  9. A Novel Cyclic PTH(1-17) analog with bone anabolic activity and efficacy sufficient to treat established osteopenia in adult ovariectomized rats

    DEFF Research Database (Denmark)

    Morko, Jukka; Peng, ZhiQi; Vääräniemi, Jukka; Rissanen, Jukka; Suominen, Mari; Fagerlund, Katja; Suutari, Tiina A.; Boonen, Harrie C.M.; Neerup, Trine S.R.; Bak, Hanne H.; Halleen, Jussi

    Recombinant human parathyroid hormone (PTH) analogs [PTH(1-34) and PTH(1-84)] are used as bone anabolic agents in clinical practice. Hitherto, bone anabolic activity has not been observed with PTH analogs shorter than 28 amino acids in vivo. The purpose of this study was to characterize effects of...... trabecular bone exacerbated in OVX rats treated with vehicle. Treatment with ZP2307 reversed the development of osteopenia in tibial metaphysis and lumbar vertebra at all doses in a dose-dependent manner, and enhanced bone formation on their trabecular bone surface at the dose of 200.0 µg/kg/d. Treatment...... with ZP2307 also reversed OVX-induced reduction in lumbar vertebral strength at the doses of 6.0-200.0 µg/kg/d and increased cortical thickness in tibial diaphysis at the doses of 60.0-200.0 µg/kg/d. Treatment with PTH(1-34) induced similar dose-dependent effects although stronger than treatment with...

  10. An osteoblast-derived proteinase controls tumor cell survival via TGF-beta activation in the bone microenvironment.

    Directory of Open Access Journals (Sweden)

    Sophie Thiolloy

    Full Text Available Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor progression in the bone microenvironment.To test our hypothesis, we utilized murine models of the osteolytic tumor-bone microenvironment in immunocompetent wild type and MMP-2 null mice. In longitudinal studies, we found that host MMP-2 significantly contributed to tumor progression in bone by protecting against apoptosis and promoting cancer cell survival (caspase-3; immunohistochemistry. Our data also indicate that host MMP-2 contributes to tumor induced osteolysis (μCT, histomorphometry. Further ex vivo/in vitro experiments with wild type and MMP-2 null osteoclast and osteoblast cultures identified that 1 the absence of MMP-2 did not have a deleterious effect on osteoclast function (cd11B isolation, osteoclast differentiation, transwell migration and dentin resorption assay; and 2 that osteoblast derived MMP-2 promoted tumor survival by regulating the bioavailability of TGFβ, a factor critical for cell-cell communication in the bone (ELISA, immunoblot assay, clonal and soft agar assays.Collectively, these studies identify a novel "mini-vicious cycle" between the osteoblast and metastatic cancer cells that is key for initial tumor survival in the bone microenvironment. In conclusion, the findings of our study suggest that the targeted inhibition of MMP-2 and/or TGFβ would be beneficial for the treatment of bone metastases.

  11. Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran; Hansen, M; Madsen, J C;

    2001-01-01

    OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and...... after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow......-acting-anti-rheumatic-drugs (SAARDs) +/- GC, the PTH secretion and calcium set point were evaluated by use of the Cica clamp technique before and after 1 month of treatment. RESULTS: S-osteocalcin, s-total alkaline phosphatase (s-TAP) and s-carboxyterminal cross-linked telopeptide of type I collagen (s-ICTP) were elevated in all...

  12. The Masticatory Contractile Load Induced Expression and Activation of Akt1/PKBα in Muscle Fibers at the Myotendinous Junction within Muscle-Tendon-Bone Unit

    Directory of Open Access Journals (Sweden)

    Yüksel Korkmaz

    2010-01-01

    Full Text Available The cell specific detection of enzyme activation in response to the physiological contractile load within muscle-tendon-bone unit is essential for understanding of the mechanical forces transmission from muscle cells via tendon to the bone. The hypothesis that the physiological mechanical loading regulates activation of Akt1/PKBα at Thr308 and at Ser473 in muscle fibers within muscle-tendon-bone unit was tested using quantitative immunohistochemistry, confocal double fluorescence analysis, and immunoblot analysis. In comparison to the staining intensities in peripheral regions of the muscle fibers, Akt1/PKBα was detected with a higher staining intensity in muscle fibers at the myotendinous junction (MTJ areas. In muscle fibers at the MTJ areas, Akt1/PKBα is dually phosphorylated at Thr308 and Ser473. The immunohistochemical results were confirmed by immunoblot analysis. We conclude that contractile load generated by masticatory muscles induces local domain-dependent expression of Akt1/PKBα as well as activation by dually phosphorylation at Thr308 and Ser473 in muscle fibers at the MTJ areas within muscle-tendon-bone unit.

  13. Role of erythropoietin in the angiogenic activity of bone marrow endothelial cells of MGUS and multiple myeloma patients.

    Science.gov (United States)

    Lamanuzzi, Aurelia; Saltarella, Ilaria; Ferrucci, Arianna; Ria, Roberto; Ruggieri, Simona; Racanelli, Vito; Rao, Luigia; Annese, Tiziana; Nico, Beatrice; Vacca, Angelo; Ribatti, Domenico

    2016-03-22

    Increasing evidences suggest several biological roles for erythropoietin and its receptor (Epo and EpoR), unrelated to erythropoiesis, including angiogenesis. Here, we detected the expression of EpoR in bone marrow-derived endothelial cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients (MGECs and MMECs, respectively) and assessed whether Epo plays a role in MGECs- and MMECs-mediated angiogenesis. We show that EpoR is expressed by both MGECs and MMECs even though at a higher level in the first ones. Both EC types respond to rHuEpo in terms of cell proliferation, whereas other responses, including activation of JAK2/STAT5 and PI3K/Akt pathways, cell migration and capillarogenesis are enhanced by Epo in MGECs, but not in MMECs. In addition, the conditioned media of both Epo-treated cells induce a strong angiogenic response in vivo in the chorioallantoic membrane assay, comparable to that of vascular endothelial growth factor (VEGF). Overall, these data highlight the effect of Epo on MGECs- and MMECs-mediated angiogenesis: MGECs are more responsive to Epo treatment than MMECs, probably because over-angiogenic phenotype of MMECs is already activated by their autocrine/paracrine loops occurring in the "angiogenic switch" from MGUS. PMID:26919105

  14. Role of erythropoietin in the angiogenic activity of bone marrow endothelial cells of MGUS and multiple myeloma patients

    Science.gov (United States)

    Ferrucci, Arianna; Ria, Roberto; Ruggieri, Simona; Racanelli, Vito; Rao, Luigia; Annese, Tiziana; Nico, Beatrice; Vacca, Angelo; Ribatti, Domenico

    2016-01-01

    Increasing evidences suggest several biological roles for erythropoietin and its receptor (Epo and EpoR), unrelated to erythropoiesis, including angiogenesis. Here, we detected the expression of EpoR in bone marrow-derived endothelial cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients (MGECs and MMECs, respectively) and assessed whether Epo plays a role in MGECs- and MMECs-mediated angiogenesis. We show that EpoR is expressed by both MGECs and MMECs even though at a higher level in the first ones. Both EC types respond to rHuEpo in terms of cell proliferation, whereas other responses, including activation of JAK2/STAT5 and PI3K/Akt pathways, cell migration and capillarogenesis are enhanced by Epo in MGECs, but not in MMECs. In addition, the conditioned media of both Epo-treated cells induce a strong angiogenic response in vivo in the chorioallantoic membrane assay, comparable to that of vascular endothelial growth factor (VEGF). Overall, these data highlight the effect of Epo on MGECs- and MMECs-mediated angiogenesis: MGECs are more responsive to Epo treatment than MMECs, probably because over-angiogenic phenotype of MMECs is already activated by their autocrine/paracrine loops occurring in the “angiogenic switch” from MGUS. PMID:26919105

  15. Bone regeneration with active angiogenesis by basic fibroblast growth factor gene transfected mesenchymal stem cells seeded on porous β-TCP ceramic scaffolds

    International Nuclear Information System (INIS)

    Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on combining gene transfer with tissue engineering techniques. Basic fibroblast growth factor (bFGF) is one of the most prominent osteogenic growth factors that has the potential to accelerate bone healing by promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) and the regeneration of capillary vasculature. However, the short biological half-lives of growth factors may impose severe restraints on their clinical usefulness. Gene-based delivery systems provide a better way of achieving a sustained high concentration of growth factors locally in the defect and delivering a more biologically active product than that achieved by exogenous application of recombinant proteins. The objective of this experimental study was to investigate whether the bFGF gene modified MSCs could enhance the repair of large segmental bone defects. The pcDNA3-bFGF gene transfected MSCs were seeded on biodegradable porous β tricalcium phosphate (β-TCP) ceramics and allografted into the 15 mm critical-sized segmental bone defects in the radius of 18 New Zealand White rabbits. The pcDNA3 vector gene transfected MSCs were taken as the control. The follow-up times were 2, 4, 6, 8, 10 and 12 weeks. Scanning electron microscopic, roentgenographic, histologic and immunohistological studies were used to assess angiogenesis and bone regeneration. In vitro, the proliferation and differentiation of bFGF gene transfected MSCs were more active than that of the control groups. In vivo, significantly more new bone formation accompanied by abundant active capillary regeneration was observed in pores of the ceramics loaded with bFGF gene transfected MSCs, compared with control groups. Transfer of gene encoding bFGF to MSCs increases their osteogenic properties by enhancing capillary regeneration, thus providing a rich blood supply for new bone formation. This new b

  16. Bone tumor

    Science.gov (United States)

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  17. Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cells

    DEFF Research Database (Denmark)

    Andersen, Thomas L; Søe, Kent; Søndergaard, Teis Esben;

    2010-01-01

    Osteolytic lesions are a hallmark of multiple myeloma. They are due to the hyperactivity of bone resorbing osteoclasts and hypoactivity of bone forming osteoblasts, in response to neighbouring myeloma cells. This study identified a structure that deeply affects this response, because of its impact...... on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy....... Importantly, this disruption and increased proximity and density of myeloma cells coincides with key myeloma-induced bone events, such as osteolytic lesions, impaired bone formation despite increased bone resorption, and fusion of myeloma cells with osteoclasts thereby forming myeloma-osteoclast hybrid cells...

  18. Soluble perlecan domain i enhances vascular endothelial growth factor-165 activity and receptor phosphorylation in human bone marrow endothelial cells

    Directory of Open Access Journals (Sweden)

    Gomes Ronald R

    2010-11-01

    Full Text Available Abstract Background Immobilized recombinant perlecan domain I (PlnDI binds and modulates the activity of heparin-binding growth factors, in vitro. However, activities for PlnDI, in solution, have not been reported. In this study, we assessed the ability of soluble forms to modulate vascular endothelial growth factor-165 (VEGF165 enhanced capillary tube-like formation, and VEGF receptor-2 phosphorylation of human bone marrow endothelial cells, in vitro. Results In solution, PlnDI binds VEGF165 in a heparan sulfate and pH dependent manner. Capillary tube-like formation is enhanced by exogenous PlnDI; however, PlnDI/VEGF165 mixtures combine to enhance formation beyond that stimulated by either PlnDI or VEGF165 alone. PlnDI also stimulates VEGF receptor-2 phosphorylation, and mixtures of PlnDI/VEGF165 reduce the time required for peak VEGF receptor-2 phosphorylation (Tyr-951, and increase Akt phosphorylation. PlnDI binds both immobilized neuropilin-1 and VEGF receptor-2, but has a greater affinity for neuropilin-1. PlnDI binding to neuropilin-1, but not to VEGF receptor-2 is dependent upon the heparan sulfate chains adorning PlnDI. Interestingly, the presence of VEGF165 but not VEGF121 significantly enhances PlnDI binding to Neuropilin-1 and VEGF receptor-2. Conclusions Our observations suggest soluble forms of PlnDI are biologically active. Moreover, PlnDI heparan sulfate chains alone or together with VEGF165 can enhance VEGFR-2 signaling and angiogenic events, in vitro. We propose PlnDI liberated during basement membrane or extracellular matrix turnover may have similar activities, in vivo.

  19. Polycythemia is associated with bone loss and reduced osteoblast activity in mice

    NARCIS (Netherlands)

    Oikonomidou, P R; Casu, C; Yang, Z; Crielaard, B; Shim, J H; Rivella, S; Vogiatzi, M G

    2015-01-01

    Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important

  20. Autologous cranial particulate bone graft: an experimental study of onlay cranioplasty.

    Science.gov (United States)

    Clune, James E; Mulliken, John B; Glowacki, Julie; Arany, Praveen R; Kulungowski, Ann M; Rogers, Gary F; Greene, Arin K

    2011-01-01

    The purpose of this study was to determine whether particulate bone graft maintains its volume when used for onlay cranioplasty. Twenty-five adult, male, New Zealand white rabbits were divided into 5 groups (n = 5/group). Groups 1 to 3 were controls: group 1, untreated; group 2, sham procedure; and group 3, burring the cortical surface. Group s 4 and 5 had augmentation of the parietal bones with particulate graft harvested from the frontal bone with a brace and bit. The particulate graft was placed on native parietal bone (group 4) or on parietal bone that had been abraded to punctuate bleeding with an electric burr (group 5). Volume maintenance and osseointegration of the grafts were determined by micro-computed tomography and histology. At 16 weeks postoperatively, the mean (SD) volumes of the parietal bones in control groups 1, 2, and 3 were 555.8 (29.2), 550.8 (36.8), and 539.0 (39.0) mm, respectively. Immediately after cranioplasty, the mean (SD) volumes of augmented parietal bone were 846.0 (10.8) mm for group 4 and 831.8 (11.8) mm for group 5. Sixteen weeks postoperatively, 100% of the group 4 grafts had resorbed (551.8 [SD, 24.0] mm), and parietal volume was no different from controls (P = 0.89). Group 5 maintained 54.2% of volume (695.6 [SD, 22.0] mm), which was greater than those of the controls (P < 0.0001). Particulate graft may be used for onlay cranioplasty if the recipient site is burred. Approximately one half of the onlay graft is resorbed, and its original shape is not maintained. PMID:21239926

  1. Antibiotic-decorated titanium with enhanced antibacterial activity through adhesive polydopamine for dental/bone implant

    OpenAIRE

    He, Shu; Zhou, Ping; Wang, Linxin; Xiong, Xiaoling; Zhang, Yifei; Deng, Yi; Wei, Shicheng

    2014-01-01

    Implant-associated infections, which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, practical approaches to prevent implant-associated infections are in great demand. Inspired by adhesive proteins in mussels, here we have developed a novel antibiotic-decorated titanium (Ti) material with enhanced antibacterial activity. In this study, Ti substrate was coated by one-step pH-induced polymerization of dopamine...

  2. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia

    OpenAIRE

    Tran, Eric; Chinnasamy, Dhanalakshmi; Yu, Zhiya; Morgan, Richard A.; Lee, Chyi-Chia Richard; Restifo, Nicholas P; Rosenberg, Steven A.

    2013-01-01

    Fibroblast activation protein (FAP) is a candidate universal target antigen because it has been reported to be selectively expressed in nearly all solid tumors by a subset of immunosuppressive tumor stromal fibroblasts. We verified that 18/18 human tumors of various histologies contained pronounced stromal elements staining strongly for FAP, and hypothesized that targeting tumor stroma with FAP-reactive T cells would inhibit tumor growth in cancer-bearing hosts. T cells genetically engineered...

  3. The feasibility of in vivo quantification of bone-gadolinium in humans by prompt gamma neutron activation analysis (PGNAA) following gadolinium-based contrast-enhanced MRI

    Science.gov (United States)

    Mostafaei, F.; McNeill, F. E.; Chettle, D. R.; Noseworthy, M. D.; Prestwich, W. V.

    2015-11-01

    The feasibility of using a 238Pu/Be-based in vivo prompt γ-ray neutron activation analysis (IVNAA) system, previously successfully used for measurements of muscle, for the detection of gadolinium (Gd) in bone was presented. Gd is extensively used in contrast agents in MR imaging. We present phantom measurement data for the measurement of Gd in the tibia. Gd has seven naturally occurring isotopes, of which two have extremely large neutron capture cross sections; 155Gd (14.8% natural abundance (NA), σ= 60,900 barns) and 157Gd (15.65% NA, σ= 254,000 barns). Our previous work focused on muscle but this only informs about the short term kinetics of Gd. We studied the possibility of measuring bone, as it may be a long term storage site for Gd. A human simulating bone phantom set was developed. The phantoms were doped with seven concentrations of Gd of concentrations 0.0, 25, 50, 75, 100, 120 and 150 ppm. Additional elements important for neutron activation analysis, Na, Cl and Ca, were also included to create an overall elemental composition consistent with Reference Man. The overall conclusion is that the potential application of this Pu-Be-based prompt in vivo NAA for the monitoring of the storage and retention of Gd in bone is not feasible.

  4. Activation, Immune Polarization, and Graft-versus-Leukemia Activity of Donor T-cells are Regulated by Specific Subsets of Donor Bone Marrow Antigen-Presenting Cells in Allogeneic Hematopoietic Stem Cell Transplantation1

    OpenAIRE

    Li, Jian-Ming; Southerland, Lauren T.; Lu, Ying; Darlak, Kataryna A.; Giver, Cynthia R.; McMillin, Douglas W.; Harris, Wayne A.C.; Jaye, David L.; Waller, Edmund K.

    2009-01-01

    We investigated the roles of specific subsets of donor APCs purified from bone marrow in donor T cell activation and graft-vs-leukemia (GvL) activity in murine models of hemopoietic stem cell transplantation. Lineage−CD11c+ APC precursors were separated from donor bone marrow based on expression of CD11b. Transplanting lineage−CD11c+CD11b− APC (CD11b− APC) in combination with c-kit+Sca-1+lineage− hemopoietic stem cells (HSC) and congenic donor T cells led to increased donor CD4+ and CD8+ T ce...

  5. Super bone scans on bone scintigraphy in patients with metastatic bone tumor

    International Nuclear Information System (INIS)

    Eight patients with malignant tumor (3 with gastric cancer, 4 with prostatic cancer, 1 with transitional cell carcinoma), which showed diffusely increased uptake of 99mTc labelled phosphorous compound in axial skeleton (''Super Bone Scan'') on bone scintigraphy were clinically studied. No relationship with its histological type of the tumor was recognized. All cases revealed extremely high serum ALP concentration, which might reflect increased osteoblastic activity. Furthermore, on bone roentgenograms all cases showed predominantly osteosclerotic change in the metastatic bones, while some did locally osteolytic change. In three cases with gastric cancer, although they had diffuse skeletal metastases, two had no evidence of liver metastases. Thus, it seemed that clinical study of patients with ''Super Bone Scan'' was interesting to evaluate the mechanism of accumulation of 99mTc labelled phosphorous compound to bone and bone metabolism, and the pathophysiology in the pathway of bone metastases. (author)

  6. Differences in xenobiotic detoxifying activities between bone marrow stromal cells from mice and rats: Implications for benzene-induced hematotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hong; Li, Yunbo; Trush, M.A. [Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD (United States)

    1995-10-01

    benzene is a human carcinogen; exposure can result in aplastic anemia and leukemia. Data from animal models are frequently used in benzene risk assessment. In rodent studies, mice are more sensitive to benzene-induced hematotoxicity than rats. Bone marrow stromal cells from mice were significantly more susceptible to the cytotoxicity induced by the benzene metabolites hydroquinone (HQ) and benzoquinone (BQ) than cells from rats. Since cellular gluthathione (GSH) and quinone reductase (QR) are known to play critical roles in modulating HQ-induced cytotoxicity, the GSH content and the QR and glutathione S-transferase (GST) activity in stromal cells from both species was measured. In rat cells, the GSH content and the QR specific activity were 2 and 28 times as much as those from mice, respectively. GSH and QR in both mouse and rat stromal cells were inducible by 1,2-dithiole-3-thione (D3T). D3T pretreatment of both mouse and rat stromal cells resulted in a marked protection against HQ-induced toxicity. Pretreatment of both mouse and rat stromal cells with GSH ethyl ester also provided a dramatic protection against HQ-induced toxicity. Conversely, dicoumarol, an inhibitor of QR, enhanced the HQ-induced toxicity in stromal cells from both mice and rats, indicating an important role for QR in modulating HQ-induced stromal toxicity. Buthionine sulfoximine (BSO), which depleted GSH significantly in both species, potentiated the HQ-induced toxicity in mouse but not in rat stromal cells. Surprisingly, incubation of stromal cells with BSO resulted in a significant induction of QR, especially in rats. Overall, this study demonstrates that the differences in stromal cellular GSH content and QR activity between mice and rats contribute to their respective susceptibility to HQ-induced cytotoxicity in vitro, and may be involved in the greater in vivo sensitivity of mice to benzene-induced hematotoxicity. 51 refs., 9 figs., 1 tab.

  7. 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.

  8. Effects of Habitual Physical Activity and Fitness on Tibial Cortical Bone Mass, Structure and Mass Distribution in Pre-pubertal Boys and Girls: The Look Study.

    Science.gov (United States)

    Duckham, Rachel L; Rantalainen, Timo; Ducher, Gaele; Hill, Briony; Telford, Richard D; Telford, Rohan M; Daly, Robin M

    2016-07-01

    Targeted weight-bearing activities during the pre-pubertal years can improve cortical bone mass, structure and distribution, but less is known about the influence of habitual physical activity (PA) and fitness. This study examined the effects of contrasting habitual PA and fitness levels on cortical bone density, geometry and mass distribution in pre-pubertal children. Boys (n = 241) and girls (n = 245) aged 7-9 years had a pQCT scan to measure tibial mid-shaft total, cortical and medullary area, cortical thickness, density, polar strength strain index (SSIpolar) and the mass/density distribution through the bone cortex (radial distribution divided into endo-, mid- and pericortical regions) and around the centre of mass (polar distribution). Four contrasting PA and fitness groups (inactive-unfit, inactive-fit, active-unfit, active-fit) were generated based on daily step counts (pedometer, 7-days) and fitness levels (20-m shuttle test and vertical jump) for boys and girls separately. Active-fit boys had 7.3-7.7 % greater cortical area and thickness compared to inactive-unfit boys (P fitness categories in girls, but active-fit girls had 6.1 % (P fit girls, which was likely due to their 6.7 % (P fit girls. Higher levels of habitual PA-fitness were associated with small regional-specific gains in 66 % tibial cortical bone mass in pre-pubertal children, particularly boys. PMID:26983726

  9. The expression of osteoprotegerin(OPG)and receptor activator nuclear factorκ-B ligand(RANKL)in pediatric bone tumor-like lesions (simple bone cysts and aneurysmal bone cysts)%OPG 及 RANKL 在小儿单纯性骨囊肿与动脉瘤样骨囊肿中的表达研究

    Institute of Scientific and Technical Information of China (English)

    宋得夫; 毕波; 邵景范; 杨小进; 王小林

    2015-01-01

    目的:检测小儿单纯性骨囊肿和动脉瘤样骨囊肿标本中骨保护素(OPG)、核因子-kB 受体活化因子配体(RANKL)的表达水平,并与正常骨组织作对照,分析两种蛋白在这两种瘤样病变中的表达是否存在差异及意义。方法共收集小儿单纯性骨囊肿标本31例,动脉瘤样骨囊肿标本23例,正常骨组织标本(对照组)14例。采用免疫组化 SABC 方法检测单纯性骨囊肿、动脉瘤样骨囊肿和对照组中 OPG、RANKL 的表达,并分析其差异性。应用 Imagepro-Plus 6.0图像处理软件及数据处理软件SPSS17.0对图像及所得数据进行分析。结果在单纯性骨囊肿及动脉瘤样骨囊肿中,OPG 的表达量均低于正常骨组织,RANKL 的表达量均高于正常骨组织,其中动脉瘤样骨囊肿 RANKL 的表达量较单纯性骨囊肿更高,差异有统计学意义(P <0.05);单纯性骨囊肿的 OPG 稍高于动脉瘤样骨囊肿,差异无统计学意义(P >0.05)。RANKL/OPG 比值动脉瘤样骨囊肿>单纯性骨囊肿>正常组织,差异有统计学意义(P <0.05)。结论RANKL/OPG 失衡可能是小儿单纯性骨囊肿和动脉瘤样骨囊肿出现溶骨性破坏的原因之一,动脉瘤样骨囊肿术后相对更高的复发率可能与 RANKL 的相对高表达有关。%Objetive To explore the expression of osteoprotegerin (OPG)and receptor activator nuclear factor κ-B ligand (RANKL)in pediatric bone tumor-like lesions (bone cysts,aneurysmal bone cysts). Methods 31 specimens of simple bone cysts,23 of aneurysmal bone cysts were collected during surgery and were taken as experimental group.Normal bone tissues from 14 patients were collected as normal controls.The expressions of OPG and RANKL were detected by immunohistochemical staining and quantified by computer image analysis software.Results Compared with normal controls,the expression of RANKL was significantly higher in simple

  10. OPG 及 RANKL 在小儿单纯性骨囊肿与动脉瘤样骨囊肿中的表达研究%The expression of osteoprotegerin(OPG)and receptor activator nuclear factorκ-B ligand(RANKL)in pediatric bone tumor-like lesions (simple bone cysts and aneurysmal bone cysts)

    Institute of Scientific and Technical Information of China (English)

    宋得夫; 毕波; 邵景范; 杨小进; 王小林

    2015-01-01

    Objetive To explore the expression of osteoprotegerin (OPG)and receptor activator nuclear factor κ-B ligand (RANKL)in pediatric bone tumor-like lesions (bone cysts,aneurysmal bone cysts). Methods 31 specimens of simple bone cysts,23 of aneurysmal bone cysts were collected during surgery and were taken as experimental group.Normal bone tissues from 14 patients were collected as normal controls.The expressions of OPG and RANKL were detected by immunohistochemical staining and quantified by computer image analysis software.Results Compared with normal controls,the expression of RANKL was significantly higher in simple bone cysts and aneurysmal bone cysts,whereas the expression of OPG was significantly lower (P 0.05).The aneurysmal bone cysts had the highest ratio of RANKL to OPG,followed by simple bone cysts,then the normal controls (P <0.05). Con-clusions Abnormal expression of RANKL and OPG is associated with pediatric bone tumor-like lesions like simple bone cysts and aneurysmal bone cysts.%目的:检测小儿单纯性骨囊肿和动脉瘤样骨囊肿标本中骨保护素(OPG)、核因子-kB 受体活化因子配体(RANKL)的表达水平,并与正常骨组织作对照,分析两种蛋白在这两种瘤样病变中的表达是否存在差异及意义。方法共收集小儿单纯性骨囊肿标本31例,动脉瘤样骨囊肿标本23例,正常骨组织标本(对照组)14例。采用免疫组化 SABC 方法检测单纯性骨囊肿、动脉瘤样骨囊肿和对照组中 OPG、RANKL 的表达,并分析其差异性。应用 Imagepro-Plus 6.0图像处理软件及数据处理软件SPSS17.0对图像及所得数据进行分析。结果在单纯性骨囊肿及动脉瘤样骨囊肿中,OPG 的表达量均低于正常骨组织,RANKL 的表达量均高于正常骨组织,其中动脉瘤样骨囊肿 RANKL 的表达量较单纯性骨囊肿更高,差异有统计学意义(P <0.05);单纯性骨囊肿的 OPG 稍高于动脉瘤样骨囊肿,

  11. Effect of low lead doses in vitro and in vivo on the d-ala-d activity of erythrocytes, bone marrow cells, liver and brain of the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Schlick, E.; Mengel, K.; Friedberg, K.D.

    1983-07-01

    The d-ala-d activity in erythrocytes (RBC), femur bone marrow, liver and brain of mice was determined using a modification of the method of Berlin and Schaller. In vitro incubation of lead acetate (PbAc) with these tissues resulted in a dose-dependent inhibition of the d-ala-d activity. The lead concentration which caused a 50% inhibition of the d-ala-d activity after 10 min incubation (ED-50sub((10min))) was 0.78 mg PbAc/femur bone marrow, 3.72 ..mu..g PbAc/ml RBC, 15.85 ..mu..g PbAc/g brain and 43.05 ..mu..g PbAc/g liver. An increase in the incubation time to 60 min reduced these ED-50 values between 44% for the erythrocytic enzyme and 67% for the brain enzyme. In vivo treatment of mice with oral lead administration (absorbed dose range: 1-100 ..mu..g PbAc/kg b.w.) for 1 or 3 months led to a dose-dependent and organ-specific inhibition of the d-ala-d activity. After 3 months of oral lead supply the maximum enzyme inhibition (54%) was found in the bone marrow. At the same time the lowest enzyme inhibition could be seen in the brain which retained 73% of its activity. The erythrocytic and liver enzyme activity was 71% and 72% resp. of the appropriate control. Within 3 weeks after completing the oral lead administration the brain enzyme activity was completely restored. The erythrocytic and liver enzyme activities were still significantly, but not very markedly inhibited, whereas the bone marrow d-ala-d remained seriously depressed. According to these experiments, the lead dose which causes a long term inhibition of the bone marrow and erythrocytic d-ala-d activities is assumed to range between 50 and 100 ..mu..g PbAc/kg b.w. and day, as an absorbed dose.

  12. Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

    Science.gov (United States)

    Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

  13. Benzene activates caspase-4 and -12 at the transcription level, without an association with apoptosis, in mouse bone marrow cells lacking the p53 gene

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Jung-Yeon; Han, Jeong-Hee; Yoon, Byung-Il [Kangwon National University, School of Veterinary Medicine, Chuncheon, Gangwon (Korea); Hirabayashi, Yoko; Kodama, Yukio; Kanno, Jun [National Institute of Health Sciences, Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, Tokyo (Japan); Choi, Yang-Kyu [Konkuk University, College of Veterinary Medicine, Seoul (Korea); Inoue, Tohru [National Institute of Health Sciences, Biological Safety and Research Center, Tokyo (Japan)

    2009-08-15

    level of mRNA and proteins. These results indicated that upregulation of caspase-4 and -12 in mice lacking the p53 gene is not associated with cellular apoptosis. In conclusion, caspase-4 and -12 can be activated by benzene treatment without inducing cell apoptosis in mouse bone marrow, which are partly under the regulation of the p53 gene. (orig.)

  14. Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone pain model by inhibiting ubiquitin and glial activation

    Science.gov (United States)

    Cheng, Wei; Chen, Yuan-Li; Wu, Liang; Miao, Bei; Yin, Qin; Wang, Jin-Feng; Fu, Zhi-Jian

    2016-01-01

    The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated pain facilitation by down-regulation of ubiquitin expression and glial activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed and increased in the spines of CIBP rats, that glial activation also increased in the CIBP model and that inhibition of spinal UCHL1 may be an effective method to alleviate cancer-induced bone pain. PMID:27508024

  15. Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

    Science.gov (United States)

    Vincenzi, Bruno; Gaeta, Laura; Pantano, Francesco; Russo, Antonio; Ortega, Cinzia; Porta, Camillo; Galluzzo, Sara; Armento, Grazia; La Verde, Nicla; Caroti, Cinzia; Treilleux, Isabelle; Ruggiero, Alessandro; Perrone, Giuseppe; Addeo, Raffaele; Clezardin, Philippe; Muda, Andrea Onetti; Tonini, Giuseppe

    2011-01-01

    Background Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that “RANK-negative” and “RANK-positive” patients had a SDFS of 105.7 months (95% CI: 73.9–124.4) and 58.9 months (95% CI: 34.7–68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients. PMID:21559440

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

    DEFF Research Database (Denmark)

    Nielsen, Michelle Christine; Bertelsen, Tomas Martin; Friis, Morten; Winther, Ole; Friis‐Hansen, Lennart; Cayé‐Thomasen, Per; Sørensen, Mads Sølvsten

    2014-01-01

    260 genes were identified of which 22 genes were involved in bone metabolism. Gene set analysis revealed five enriched bone‐related gene sets. The identified differentially expressed bone‐related mRNAs and gene sets are of potential significance in the normally developing bulla. These factors and gene......Common middle ear diseases may affect bone behavior in the middle ear air cell system. To understand this pathologic pneumatization, the normal development of bone in the middle ear should be investigated. The objective of this study was to analyze gene expression of bone‐related signaling factors...... and gene sets in the developing middle ear. Microarray technology was used to identify bone‐related genes and gene sets, which were differentially expressed between the lining tissue of adult (quiescent) bulla and young (resorbing/forming) bulla. Data were analyzed using tools of bioinformatics and...

  17. Immunoregulation of bone remodelling

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  18. The osteogenic differentiation stimulating activity of Sea cucumber methanolic crude extraction on rat bone marrow mesenchymal stem cells

    OpenAIRE

    Javad Baharara; Elaheh Amini; Mohammad Amin Kerachian; Mozhgan Soltani

    2014-01-01

    Objective(s): Sea cucumber derived bioactive compound is considered efficient in treatment of bone disorders. This study was performed to evaluate the effect of this extract on differentiation of rat bone marrow mesenchymal stem cells (rBMMSc) into osteogenic lineage. Materials and Methods: Isolated rBMMSc were grown in DMEM supplemented with 10% FBS. The cells were exposed to different concentration of extract. After 21 days, Alizarin red staining, alkaline phosphatase assay and RT-PCR were ...

  19. Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.

    Science.gov (United States)

    Zhang, Wenjie; Chang, Qing; Xu, Ling; Li, Guanglong; Yang, Guangzheng; Ding, Xun; Wang, Xiansong; Cui, Daxiang; Jiang, Xinquan

    2016-06-01

    Graphene has been studied for its in vitro osteoinductive capacity. However, the in vivo bone repair effects of graphene-based scaffolds remain unknown. The aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. The GO-Cu nanocomposites, containing crystallized CuO/Cu2 O nanoparticles of ≈30 nm diameters, distribute uniformly on the surfaces of the porous scaffolds and maintain a long-term release of Cu ions. In vitro, the GO-Cu coating enhances the adhesion and osteogenic differentiation of rat bone marrow stem cells (BMSCs). It is also found that by activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins. When transplanted into rat with critical-sized calvarial defects, the GO-Cu-coated calcium phosphate cement (CPC) scaffolds (CPC/GO-Cu) significantly promote angiogenesis and osteogenesis. Moreover, it is observed via histological sections that the GO-Cu nanocomposites are phagocytosed by multinucleated giant cells. The results suggest that GO-Cu nanocomposite coatings can be utilized as an attractive strategy for vascularized bone regeneration. PMID:26945787

  20. A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, H; Jensen, Ole N; Moiseeva, Elena P;

    2003-01-01

    , which induced hBMS cell proliferation by 3-fold. This effect was abolished by IGF-I. PC3 CM and galectin-1 in concentrations of 10 and 1000 ng/ml increased the alkaline phosphatase (ALP) activity of hBMS cells up to 175 +/- 27%, 137 +/- 8%, and 131 +/- 11%, respectively, compared with ALP activity of......Prostate cancer cells metastasize to bone causing a predominantly osteosclerotic response. It has been shown that cells from the human prostate cancer cell line PC3 secrete factors that influence the behavior of osteoblast-like cells. Some of these factors with mitogenic activity have been found to...

  1. Physical activity based intervention program on health, bone mineral density and fitness status for rheumatology patient over 60 years of age

    Directory of Open Access Journals (Sweden)

    Kopkáné Plachy Judit

    2014-11-01

    Full Text Available Study aim: regular physical activity is important both for the prevention of illnesses and for rehabilitation purposes because it has significant impact on the physical and mental health of the elderly. The purpose of this study was to assess whether two different half-year regular training programmes had positive effects on health dimensions, bone mineral density, and fitness status in population of women aged over 60 years.

  2. Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord

    OpenAIRE

    Cheng Hao; Ji Fu-hai; Zhang Yan-bing; Li Cai-fang; Peng Yan; Peng Jun; Yang Jian-ping; Yao Ming; Wang Li-na; Xu Qi-nian; Wang Xiu-yun; Zuo Jian-ling

    2011-01-01

    Abstract Background Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed...

  3. Cellular Mechanisms of Multiple Myeloma Bone Disease

    OpenAIRE

    Angela Oranger; Claudia Carbone; Maddalena Izzo; Maria Grano

    2013-01-01

    Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and d...

  4. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

    Science.gov (United States)

    Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

    2016-09-01

    Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. PMID:26051481

  5. Improvements in an in vivo neutron activation analysis (NAA) method for the measurement of fluorine in human bone

    International Nuclear Information System (INIS)

    We previously published a method for the in vivo measurement of bone fluoride using neutron activation analysis (NAA) and demonstrated the utility of the technique in a pilot study of environmentally exposed people. The method involved activation of the hand in an irradiation cavity at the McMaster University Accelerator Laboratory and acquisition of the resultant γ-ray signals in a ‘4π’ NaI(Tl) detector array of nine detectors. In this paper we describe a series of improvements to the method. This was investigated via measurement of hand simulating phantoms doped with varying levels of fluorine and fixed amounts of sodium, chlorine and calcium. Four improvements to the technique were tested since our first publication. The previously published detection limit for phantom measurements using this system was 0.66 mg F/g Ca. The accelerator irradiation and detection facilities were relocated to a new section of the laboratory and one more detector was added to the detection system. This was found to reduce the detection limit (possibly because of better detection shielding and additional detector) to 0.59 mg F/g Ca, a factor of 1.12. A new set of phantoms was developed and in this work we show that they improved the minimum detectable limit for fluoride in phantoms irradiated using neutrons produced by 2.15 MeV protons on lithium by a factor of 1.55. We compared the detection limits previously obtained using a summed signal from the nine detectors with the detection limit obtained by acquiring the spectra in anticoincidence mode for reduction of the disturbing signal from chlorine in bone. This was found to improve the ratio of the detection of fluorine to chlorine (an interfering signal) by a factor of 2.8 and the resultant minimum detection limit was found to be reduced by a factor of 1.2. We studied the effects of changing the timing of γ-ray acquisition. Our previously published data used a series of three 10 s acquisitions followed by a 300 s count

  6. [Bone diseases].

    Science.gov (United States)

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  7. Bone Regeneration Using Dentin Matrix Depends on the Degree of Demineralization and Particle Size.

    Directory of Open Access Journals (Sweden)

    Takamitsu Koga

    Full Text Available This study aimed to examine the influence of particle size and extent of demineralization of dentin matrix on bone regeneration.Extracted human teeth were pulverized and divided into 3 groups according to particle size; 200, 500, and 1000 μm. Each group was divided into 3 groups depending on the extent of demineralization; undemineralized dentin (UDD, partially demineralized dentin matrix (PDDM, and completely demineralized dentin matrix (CDDM. The dentin sample was implanted into rat calvarial bone defects. After 4 and 8 weeks, the bone regeneration was evaluated with micro-CT images, histomorphometric and immunohistochemical analyses. Osteoblasts were cultured on UDD and DDM to evaluate the cell attachment using electron microscope.Micro-CT images and histological observation revealed that CDDM had largely resorbed but UDD had not, and both of them induced little bone formation, whereas all particle sizes of PDDM induced more new bone, especially the 1000 μm. Electron microscopic observation showed osteoblasts attached to DDM but not to UDD.PDDM with larger particle size induced prominent bone regeneration, probably because PDDM possessed a suitable surface for cell attachment. There might be an exquisite balance between its resorption and bone formation on it. PDDM could be considered as a potential bone substitute.

  8. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  9. The BoneXpert method for automated determination of skeletal maturity

    DEFF Research Database (Denmark)

    Thodberg, Hans Henrik; Kreiborg, Sven; Juul, Anders;

    2009-01-01

    bone morphology or very poor image quality. From the methodological point of view, BoneXpert contains the following innovations: 1) a generative model (active appearance model) for the bone reconstruction; 2) the prediction of bone age from shape, intensity, and texture scores derived from principal...... 15 bones automatically and then computes "intrinsic" bone ages for each of 13 bones (radius, ulna, and 11 short bones). Finally, it transforms the intrinsic bone ages into Greulich Pyle (GP) or Tanner Whitehouse (TW) bone age. The bone reconstruction method automatically rejects images with abnormal...... component analysis; 3) the consensus bone age concept that defines bone age of each bone as the best estimate of the bone age of the other bones in the hand; 4) a common bone age model for males and females; and 5) the unified modelling of TW and GP bone age. BoneXpert is developed on 1559 images. It is...

  10. Dynamic scintigraphy of bone and bone marrow in multiple myeloma patients with bone-marrow transplants

    International Nuclear Information System (INIS)

    Purpose: To determine whether dynamic registration at bone and bone-marrow scintigraphy produces additional information compared to subsequent static registrations of bone-marrow transplants in multiple myeloma patients. Material and Methods: In a prospective study, 8 dynamic bone and 6 dynamic bone-marrow scintigraphies were performed in 10 patients. The dynamic scintigraphies were compared with conventional radiography, MR images, and static scintigraphies of bone and bone marrow. Results: No additional information was revealed by the dynamic registration method; on the contrary, 4 of the 8 known lesions were not discerned at dynamic registration. An incidental observation was that the time-activity curves of both radiopharmaceuticals had a specific pattern. (orig.)

  11. Bone Appetit: The Role of Food and Nutrition in Building and Maintaining Strong Bones

    Science.gov (United States)

    Bone is a living, dynamic, metabolically active tissue. It under goes a process of constant renewal throughout life, through a process called bone turnover in which cells called osteoclasts remove old or damaged bone, and cells called osteoblasts make new bone to replace it. A healthy, balanced di...

  12. Peripheral bone mineral density and different intensities of physical activity in children 6-8 years old: the Copenhagen School Child Intervention study

    DEFF Research Database (Denmark)

    Hasselstrøm, H; Karlsson, K M; Hansen, S E;

    2007-01-01

    -stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more daily physical activity and spent 14.6-19.0% more...... with intense physical activity above all the chosen cut-off points (all P < 0.05). The beta value for mean count . min(-1) physical activity was significantly lower than that for all the chosen cut-off points of vigorous activity both for calcaneal and distal forearm BMD. This study suggests that both...

  13. Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile of Luteolin-7-O-glucoside Isolated from Trifolium alexandrinum L. in Ovariectomized Rats.

    Science.gov (United States)

    Ammar, N M; El-Hawary, S S; Mohamed, D A; El-Halawany, A M; El-Anssary, A A; El-Kassem, L T Abou; Hussein, R A; Jaleel, G A Abdel; El-Dosoky, A H

    2016-05-01

    Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27145225

  14. Talking Bones.

    Science.gov (United States)

    Johnson, Jaclyn; Kassing, Sharon

    2002-01-01

    Describes cooperation with the Saint Louis Zoo to provide opportunities for elementary school students to learn about bones, how animals move, what they eat, and how much they grow. Uses biofacts which include bones, skulls, and other parts to make the laboratory a hands-on experience for students. (YDS)

  15. Bone Markers

    Science.gov (United States)

    ... bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is ... resorption include: N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal ...

  16. Design of a phantom equivalent to measure bone-fluorine in a human's hand via delayed neutron activation analysis

    International Nuclear Information System (INIS)

    Fluorine is an element that can be either beneficial or harmful, depending on the total amount accumulated in the teeth or bones. In our laboratory, we have developed a non-invasive technique for the in vivo measurement of fluoride in bone using neutron activation analysis and performed the first pilot human study. Fluoride in humans is quantified by comparing the γ-ray signal from a person to the γ-ray signal obtained from appropriate anthropomorphic calibration phantoms. An identified problem with existing fluoride phantoms is contamination with aluminum. Aluminum creates an interfering γ-ray signal which, although it can be subtracted out, increases the uncertainty in the measurement and worsens the detection limit. This paper outlines a series of studies undertaken to develop a better calibration phantom for fluorine measurement, which does not have aluminum contamination. (paper)

  17. Trace rare earth element analysis of IAEA Hair (HH-1), Animal Bone (H-5) and other biological standards by radiochemical neutron activation

    International Nuclear Information System (INIS)

    A radiochemical neutron activation analysis using a rare earth group separation scheme was used to measure ultratrace levels of rare earth elements (REE) in IAEA Human Hair (HH-1), IAEA Animal Bone (H-5), NBS Bovine Liver (SRM 1577), and NBS Orchard Leaf (SRM 1571) standards. The REE concentrations in Human Hair and Animal Bone range from 10-8 g/g to 10-11 g/g and their chondritic normalized REE patterns show a negative Eu anomaly and follow as a smooth function of the REE ionic radii. The REE patterns for NBS Bovine Liver and Orchard Leaf are identical except that their concentrations are higher. The similarity among the REE patterns suggest that the REE do not appear to be fractionated during the intake of biological materials by animals or humans. (author)

  18. Test of multielement analysis of bone samples using instrumental neutron activation analysis (INAA) and anti-Compton spectrometry

    International Nuclear Information System (INIS)

    INAA and anti-Compton spectrometry has been employed in the analysis of test bone samples. Validity and accuracy of the method were checked by the use of two biological reference materials procured from the National Institute of Standards and Technology, USA (NIST) and the International Atomic Energy Agency, Austria (IAEA). NIST 1486 Bone Meal (ca. 200-800 mg) and A-11 Milk Powder (ca. 200-600 mg) samples were irradiated in the 100 kW TRIGA Mainz reactor. Concentrations of 13 elements in both biological reference materials have been determined and were found in good agreement with the certified and provisional values. (author)

  19. In vivo determination of the {sup 99m}Tc-MDP incorporated activity in bone tissue; Determinacao in vivo da atividade incorporada de {sup 99m} Tc-MDP no tecido osseo

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Joseane Fonseca; Braga, Francisco J.H.N. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras. Dept. de Fisica e Matematica; Dantas, Bernardo M.; Bertelli, Luiz [Instituto de Radioprotecao e Dosimetria (IRD), Rio de Janeiro, RJ (Brazil); Ghilardi Netto, Thomaz [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Centro de Ciencias da Imagem e Fisica Medica

    1998-07-01

    For determining in vivo {sup 99m}Tc-MDP incorporated activity in bone tissue using a scintillation chamber as a image detection and acquisition system it is necessary the system calibration using an anthropomorphic physical simulator. The development of a tibia and fibula simulator in order to estimate bone tissue activity is presented. This procedure can be used either for workers monitoring or for the metabolic behavior of this radiopharmaceutical.

  20. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  1. Bioactive Hierarchical Structures for Genetic Control of Bone Morphogenesis

    Directory of Open Access Journals (Sweden)

    Pilar Sepulveda

    2002-09-01

    Full Text Available For thirty years it has been known that certain compositions of Na2O-CaO-P2O5-SiO 2 glasses will form a mechanically strong, chemical bond to bone. These materials have become known as bioactive glasses and the process of bonding is called bioactive fixation. Bioactive glasses are widely used clinically in the repair of bone defects. Recent research at the Imperial College Tissue Engineering Centre has now established that there is a genetic control of the cellular response to bioactive materials. Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses. The gene expression occurs very rapidly, within two days, and includes enhanced expression of cell cycle regulators. The consequence is rapid differentiation of the osteoblasts into a mature phenotype and formation of large three-dimensional bone nodules within six days in vitro. These cell culture results correlate with extensive human clinical results using the same bioactive material. The new genetic theory of bioactive materials provides a scientific foundation for molecular design of new generation of resorbable bioactive materials for tissue engineering and in situ tissue regeneration and repair. Application of this theory to the synthesis of bioactive foams for tissue engineering of bone is described.

  2. Increasing weight-bearing physical activity and calcium-rich foods to promote bone mass gains among 9–11 year old girls: outcomes of the Cal-Girls study

    Directory of Open Access Journals (Sweden)

    Hannan Peter

    2005-07-01

    Full Text Available Abstract Background A two-year, community-based, group-randomized trial to promote bone mass gains among 9–11 year-old girls through increased intake of calcium-rich foods and weight-bearing physical activity was evaluated. Methods Following baseline data collection, 30 5th-grade Girl Scout troops were randomized to a two-year behavioral intervention program or to a no-treatment control group. Evaluations were conducted at baseline, one year, and two years. Measures included bone mineral content, density, and area (measured by DXA, dietary calcium intake (24-hour recall, and weight-bearing physical activity (physical activity checklist interview. Mixed-model regression was used to evaluate treatment-related changes in bone mineral content (g for the total body, lumbar spine (L1-L4, proximal femur, one-third distal radius, and femoral neck. Changes in eating and physical activity behavioral outcomes were examined. Results Although the intervention was implemented with high fidelity, no significant intervention effects were observed for total bone mineral content or any specific bone sites. Significant intervention effects were observed for increases in dietary calcium. No significant intervention effects were observed for increases in weight-bearing physical activity. Conclusion Future research needs to identify the optimal dosage of weight-bearing physical activity and calcium-rich dietary behavior change required to maximize bone mass gains in pre-adolescent and adolescent girls.

  3. Technetium-99m human polyclonal immunoglobulin g studies and conventional bone scans to detect active joint inflammation in chronic rheumatoid arthritis

    International Nuclear Information System (INIS)

    Rheumatoid arthritis is a chronic polyarthritis in which active inflammed joints coexist with joints in remission. We performed bone scans (99mTc-DPD) and 99mTc human polyclonal immunoglobulin G scans (99mTc-IgG) in 18 patients with rheumatoid arthritis to assess the uptake in actively inflammed joints and in joints in which remission after inflammation had occurred. A quantitative analysis of tracer uptake in each joint was performed on both scans. In 123 joints without current active inflammation, an increased 99mTc-DPD uptake was observed (2.31±1.27), whereas no 99mTc-IgG uptake was noted (1.18±0.32). Some 78 joints with mild pain or swelling exhibited increased 99mTc-DPD uptake (2.48±1.14) and increased 99mTc-IgG uptake (1.76±0.50; P99mTc-DPD uptake (2.39±0.93) and increased 99mTc-IgG uptake (1.79±0.51; P99mTc-IgG scans distinguish between joints with and without active inflammation in chronic rheumatoid arthritis, whereas bone scans do not. Thus, 99mTc-IgG scans may be useful in identifying joints with current active inflammation in rheumatoid arthritis. (orig.)

  4. Effects of a cloned cell line with NK activity on bone marrow transplants, tumour development and metastasis in vivo

    Science.gov (United States)

    Warner, John F.; Dennert, Gunther

    1982-11-01

    Natural killer (NK) cells cloned in vitro have been transferred into NK-deficient hosts. These cells have been shown to have a role in the rejection of allogeneic bone marrow grafts, resistance to both radiation-induced thymic leukaemia and challenge with melanoma tumour cells. It appears that NK cells have an important role in immune surveillance.

  5. A modified rabbit ulna defect model for evaluating periosteal substitutes in bone engineering: a pilot study.

    Science.gov (United States)

    El Backly, Rania M; Chiapale, Danilo; Muraglia, Anita; Tromba, Giuliana; Ottonello, Chiara; Santolini, Federico; Cancedda, Ranieri; Mastrogiacomo, Maddalena

    2014-01-01

    The present work defines a modified critical size rabbit ulna defect model for bone regeneration in which a non-resorbable barrier membrane was used to separate the radius from the ulna to create a valid model for evaluation of tissue-engineered periosteal substitutes. Eight rabbits divided into two groups were used. Critical defects (15 mm) were made in the ulna completely eliminating periosteum. For group I, defects were filled with a nanohydroxyapatite poly(ester urethane) scaffold soaked in PBS and left as such (group Ia) or wrapped with a tissue-engineered periosteal substitute (group Ib). For group II, an expanded-polytetrafluoroethylene (e-PTFE) (GORE-TEX(®)) membrane was inserted around the radius then the defects received either scaffold alone (group IIa) or scaffold wrapped with periosteal substitute (group IIb). Animals were euthanized after 12-16 weeks, and bone regeneration was evaluated by radiography, computed microtomography (μCT), and histology. In the first group, we observed formation of radio-ulnar synostosis irrespective of the treatment. This was completely eliminated upon placement of the e-PTFE (GORE-TEX(®)) membrane in the second group of animals. In conclusion, modification of the model using a non-resorbable e-PTFE membrane to isolate the ulna from the radius was a valuable addition allowing for objective evaluation of the tissue-engineered periosteal substitute. PMID:25610828

  6. Differentiation of bone marrow cells with irradiated bone in vitro

    International Nuclear Information System (INIS)

    Disease transmission or infection is an important issue in bone allograft, and irradiation is used for sterilization of graft bones. One of the advantages of bone allograft over biomaterials is that graft bones have osteoinductive factors such as growth factors. Irradiation is reported to decrease the osteoinductive activity in vivo. We investigated the osteoinductive activity of irradiated bone by alkaline phosphatase (ALP) activity in rat bone marrow cell culture. Bones (tibias and femurs of 12-week-old Wistar rats) were cleaned of adhering soft tissue, and the marrow was removed by washing. The bones were defatted, lyophilized, and cut into uniform 70 mg fragments. Then the Bone fragments were irradiated at either 10, 20, 25, 30, 40, or 50 kGy at JAERI. Bone marrow cells were isolated from tibias and femurs of 4-week-old Wistar rats. Cells were plated in tissue culture flask. When primary cultures reached confluence, cells were passaged (4 x 103 cell / cm2) to 6 wells plates. The culture medium consisted of minimum essential medium, 10% fetal bovine serum, ascorbic acid, and antibiotics. At confluence, a cell culture insert was set in the well, and an irradiated bone fragment was placed in it. Then, medium was supplemented with 10 mM ?-glycerophosphate and 1 x 10-8 M dexamethasone. Culture wells were stained by naphthol AS-MX phosphate, N,N-dimethyl formamide, Red violet LB salt on day 0, 7, 14. The density of ALP staining was analyzed by a personal computer. Without bones, ALP staining increased by 50% on day 7 and by 100% on day 14, compared with that on day 0. The other side, with bones irradiated at 30 kGy or lower, ALP staining increased by 150% on day 7, and by 180% on day 14, compared with that on day 0. In the groups of irradiated bones of 40 kGy or higher, the increase in ALP staining was less prominent compared with the groups of irradiated bones of 30 kGy or lower. In the groups of 0-30 kGy irradiation, ALP staining increased in the early period

  7. Effect of bone marrow stromal cell transplantation to the hippocampal CA1 region on electroencephalographic activity in epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Hong Xu; Guowei Xu; Zhongtang Feng; Tinghua Wang; Jia Yang; Qingying Wu; Zhicheng Xiao

    2008-01-01

    BACKGROUND: Animal experiments have confirmed that bone marrow stromal cell (BMSC) transplantation can serve as a treatment for epilepsy.OBJECTIVE: BMSCs derived from green fluorescent protein (GFP) mice were transplanted into the hippocampal CA1 region of epileptic rats. The aim of the study was to record electroencephalogram (EEG), analyze survival and migration of BMSCs, and validate the effect of BMSC transplantation for the treatment of epilepsy.DESIGN, TIME AND SETTING: A randomized block design experiment was performed at the Institute of Neuroscience, Kunming Medical College from March 200.5 to February 2006.MATERIALS: Homozygous C57BL/6CrSIcTgN (acr-EGFP) OsbC 14-Y01 -FM 131 mice, 8-12 weeks of age, were selected for preparation of cell suspension. Sprague Dawley rats were selected for establishing epilepsy models.METHODS: Rats were randomly divided into 4 groups: control (n = 8), model (n = 8), normal saline (n = 24), and BMSC (n = 24). In the model, normal saline, and BMSC groups, epilepsy was established with penicillin (3×107 U/kg i.p. ×7 days). Rats in the BMSC group received a BMSC suspension derived fromgreen fluorescent protein mice into the right hippocampal CA1 region. Rats in the vehicle control group were injected with the same volume of normal saline into the hippocampal CA1 region.MAIN OUTCOME MEASURES: The electroencephalogram was used to monitor brain activity. Survival and migration of the transplanted BMSCs was observed using fluorescence microscopy at 1, 2, and 4 weeks after transplantation.RESULTS: In BMSC group, fluorescent cells were observed at the transplantation site and in the adjacent tissue, as well as in the tissue surrounding the needle tract, indicating the migration of implanted cells. Fluorescent cells were not detected in the vehicle control group. The electroencephalogram of the control animals exhibited 7-9 Hz α waves, with a wave amplitude < 50 μ V. In the model and vehicle control groups, random spike

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

    Directory of Open Access Journals (Sweden)

    C. Rentsch

    2014-01-01

    Full Text Available Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100% and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant.

  9. ECM inspired coating of embroidered 3D scaffolds enhances calvaria bone regeneration.

    Science.gov (United States)

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

    2014-01-01

    Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

  10. Qualitative identification of the active principles in Citrullus colocynthis and evaluation of its teratogenic effects in albino rats

    Directory of Open Access Journals (Sweden)

    Amer Abdalla Elgerwi

    2013-08-01

    Full Text Available Background: This study was designed to identify the active contents of Citrullus colocynthis plant and to examine their teratogenicity in rats. The fruit pulp of the poisonous plant was collected randomly from Suq-Alkhamis district, Tripoli, Libya. Methods: The glucoside colocynthin was isolated by lead acetate method while the alkaloids and saponins were isolated by maceration method. These active principles were then identified by chemical tests, color reactions and thin layer chromatography. Possible teratogenic effects of the fruit pulp extract was investigated by its administration to twelve pregnant rats on the 7th day of gestation at a dose of 40.6 mg/kg body weight that is equivalent to one fourth of the LD50 of the extract. Results: Gross anatomical observation on the 20th day of gestation revealed a high percentage of resorbed fetuses, smaller size and weight fetuses as well as absence of coccygeal vertebrae, metacarpal and metatarsal bones, and carpal and tarsal bones. Conclusions: It could be concluded that the extract of fruit pulp of Citrullus colocynthis, obtained from Libya, contain glucosidal as well as other principles that may cause teratogenic effects if given during at the early stage of pregnancy. [Int J Basic Clin Pharmacol 2013; 2(4.000: 438-445

  11. Effects of Time of Initial Exposure to MSV Sarcoma on Bone Induction by Dentine Matrix Implants and on Orthotopic Femora

    Directory of Open Access Journals (Sweden)

    Aniela Brodzikowska

    2010-09-01

    Full Text Available HCl-demineralized murine lower incisors were implanted intramuscularly into syngeneic BALB/c mice to induce heterotopic osteogenesis. Implants were exposed at the early, preosteogenic stage (4, or at the later, osteogenic stage (12 to the Moloney sarcoma virus (MSV, which within 3–4 days results in a sarcoma. The yield of bone induction was determined by weight of dry bone mass following NaOH hydrolysis of soft tissues. To verify the effect of this sarcoma on orthotopic local femoral bone, the dry mass of the tumor-exposed femora was measured and compared with the weight of MSV-unexposed contralateral controls. MSV-sarcoma or cells involved with their spontaneous rejection have a stimulatory effect on the periosteal membrane of the tumor-adjacent femoral bones, increasing their dry mass on average by 18%. No stimulatory effect on heterotopic bone induction was observed when the MSV sarcoma grew during the early, preosteogenic stage (4 onward, but when the tooth matrix had been exposed to such tumor at the already bone-forming stage, (12 onward, the yield of bone induction was enhanced. Thus, it is postulated that lesions induced by MSV during the early, preosteogenic stage inhibit recruitment of osteoprogenitor cells or degrade Bone Morphogenetic Proteins (BMPs released by matrix resorbing inflammatory cells, whereas when acting on already existing bone they have a stimulatory effect.

  12. Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic experiment in rats.

    Science.gov (United States)

    Al-Hezaimi, Khalid; Ramalingam, Sundar; Al-Askar, Mansour; ArRejaie, Aws S; Nooh, Nasser; Jawad, Fawad; Aldahmash, Abdullah; Atteya, Muhammad; Wang, Cun-Yu

    2016-01-01

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical "lock" between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy. PMID:27025260

  13. Determination of calcium, phosphorus, and the calcium/phosphorus ratio in cortical bone from the human femoral neck by neutron activation analysis

    International Nuclear Information System (INIS)

    Concentrations of Ca and P as well as the Ca/P ratio were estimated in intact cortical bone samples from the femoral neck of healthy humans, 33 women and 45 men, aged from 15 to 55 yr using instrumental neutron activation analysis. Mean values (M±SD) for the investigated parameters (on dry weight basis) were: 23.0±3.9%, 10.7±2.4% and 2.17±0.31, respectively. No statistically significant differences of the above parameters were observed related either to age or sex. The mean values for Ca, P and Ca/P ratio were within a very wide range of published data and close to their median. The individual variation for the Ca/P ratio in cortical bone from the healthy human femoral neck was lower than those for Ca and P separately. This means that specificity of Ca/P ratio is better than those of Ca and P concentrations are and may be more reliable for diagnosis of bone disorders

  14. Bone morphogenetic proteins: Periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Subramaniam M Rao

    2013-01-01

    Full Text Available Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search. All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP.

  15. Cytotoxic Effects and Osteogenic Activity of Calcium Sulfate with and without Recombinant Human Bone Morphogenetic Protein 2 and Nano-Hydroxyapatite Adjacent to MG-63 Cell Line

    Directory of Open Access Journals (Sweden)

    Abdollah Ghorbanzadeh

    2015-10-01

    Full Text Available Objectives: The aim of this study was to assess the cytotoxic effects and osteogenic activity of recombinant human bone morphogenetic protein (rhBMP2 and nano-hydroxyapatite (n- HA adjacent to MG-63 cell line.Materials and Methods: To assess cytotoxicity, the 4,5-dimethyl thiazolyl-2,5-diphenyl tetrazolium bromide (MTT assay was used. Alkaline phosphatase (ALP activity and oste- ogenic activity were evaluated using Alizarin red and the von Kossa staining and analyzed by one-way ANOVA followed by Tukey’s post hoc test.Results: The n-HA/CS mixture significantly promoted cell growth in comparison to pure calcium sulfate (CS. Moreover, addition of rhBMP2 to CS (P=0.02 and also mixing CS with n-HA led to further increase in extracellular calcium production and ALP activity (P=0.03.Conclusion: This in vitro study indicates that a scaffold material in combination with an osteoinductive material is effective for bone matrix formation.

  16. Instrumental neutron-activation analysis applications in the age dynamics assessment of Ca, Cl, K, Mg. Mn, Na, P, and Sr contents in the human cortical bone

    International Nuclear Information System (INIS)

    Full text: Senile osteoporosis and particularly osteoporosis among postmenopausal women represents an urgent problem of modern medicine. One of the main osteoporosis symptoms is a decrease in both bone mineral density and subsequent bone strength. The upper extremity of the femur in humans is a particularly vulnerable section of the skeleton, being subject to fracture and necrosis and to destruction of its cartilage. Iliac crest biopsies are commonly taken clinically on patients. It is known that the control of the mineral component providing bone strength is a good indicator to detect bone diseases like osteoporosis. Despite this, changes of chemical element contents occurring with age in the femoral head and the iliac crest of female and male separately have been little studied, but in iliac cortical bone have not been studied at all. The effect of age and sex on chemical element contents in intact cortical bone of femoral neck and iliac crest of 81 relatively healthy 15-55 years old women (n=36) and men (n=45) was investigated. All subjects had died suddenly and bone samples were obtained at necropsy from the right side of bodies within twenty-four hours after death. A tool made of titanium and plastic was used to clear samples from soft tissues and blood and to cut cortical part of bone. The IAEA and NIST reference materials (H-5 animal bone and SRM1486 bone meal) were used to estimate the precision and accuracy of results. Contents of Ca, Cl, K, Mg> Mn, Na, P, and Sr in intact bone samples were determined by instrumental neutron activation analysis using short-lived radionuclides. Our means data for each element of reference materials were within the certified 95 % confidence interval, and indicate an acceptable accuracy of the obtained results. No age- and sex-related differences in the cortical femoral neck composition were detected. Mean values (M±S.E.M.) of Ca, Cl, K, Mg, Mn, Na, P, and Sr mass fractions (on dry weight basis) for female and male all

  17. Comparison of bone scanning and bone-marrow scintigraphy in the detection and monitoring of bone metastases

    International Nuclear Information System (INIS)

    The purpose of this review is to define the role of bone scanning and bone-marrow scintigraphy in the detection and monitoring of skeletal metastasis. The bone scan has remained the screening method of choice for many years, because of its exquisite sensitivity for lesion detection and its ability to evaluate the whole skeleton in one setting. Bone-marrow scintigraphy with 99mTc-labelled antigranulocyte monoclonal antibodies allows high-quality, whole-body visualization of hematopoetically active bone marrow. The importance of imaging the bone marrow is founded in the fact that, in general, bone-marrow invasion precedes skeletal involvement in the development of skeletal metastasis. The advantages and disadvantages of the two methods are compared, and the possible indications for using bone-marrow scintigraphy complementary to or instead of the bone scan are discussed. (orig.)

  18. Bone Tumor

    Science.gov (United States)

    ... the knee in either the femur (thigh) or tibia (shinbone). Other common locations include the hip and ... bone that is weakened by a tumor to fracture, or break. This may be severely painful. Occasionally, ...

  19. Your Bones

    Science.gov (United States)

    ... a fall! If you play sports like football, soccer, lacrosse, or ice hockey, always wear all the ... to strengthen your bones is through exercise like running, jumping, dancing, and playing sports. Take these steps ...

  20. Short-term behaviour of two similar active glasses used as granules in the repair of bone defects.

    Science.gov (United States)

    Gatti, A M; Zaffe, D

    1991-07-01

    The bioactivity of two similar vitreous materials used in the form of granules of 'critical' size was investigated in bone defects in jaws of two sheep. The granules consisted of Hench's Bioglass and another glass with the same chemical composition made in Italy. Two months after implantation, the sheep were killed and elemental analyses carried out on sections of the embedded jaws. The microanalyses for both the glasses showed a diffusion from the granules towards the surrounding tissue of silicon and sodium, and an inverse diffusion (from the surrounding tissue towards the granules) of calcium and phosphorus. The degradation for the Italian glass was slower than for the Bioglass. No significant osteoinduction was seen after that time at the interface of the glass granules or in the bone pocket. PMID:1892986

  1. Androgen and bone mass in men

    Institute of Scientific and Technical Information of China (English)

    AnnieW.C.Kung

    2003-01-01

    Androgens have multiple actions on the skeleton throughout life. Androgens promote skeletal growth and accumulation of minerals during puberty and adolescence and stimulate osteoblast but suppress osteoclast function,activity and lifespan through complex mechanisms. Also androgens increase periosteal bone apposition, resulting in larger bone size and thicker cortical bone in men. There is convincing evidence to show that aromatization to estrogens was an important pathway for mediating the action of testosterone on bone physiology. Estrogen is probably the dominant sex steroid regulating bone resorption in men, but both testosterone and estrogen are important in maintaining bone formation. ( Asian J Androl 2003 Jun; 5: 148-154)

  2. Novel polysaccharide anti-tumour drug delivery system for active targeting and controlled release to breast cancer bone metastases

    OpenAIRE

    Bonzi, Gwénaëlle A.M.

    2014-01-01

    ABSTRACT In the late stage of the disease, breast cancer patients often develop bone metastases, a major cause of cancer-related death among women worldwide. The common treatment currently used clinically includes the anti-neoplastic agent paclitaxel combined with the bisphosphonate alendronate. Paclitaxel is an anti-neoplastic drug which cytotoxic effect is mainly attributed to its ability to promote the assembly of microtubules as well as prevent the depolymerisation of these micro...

  3. LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation

    OpenAIRE

    Cooke, Kenneth R.; Gerbitz, Armin; Crawford, James M.; Teshima, Takanori; Hill, Geoffrey R.; Tesolin, Amy; Rossignol, Daniel P.; Ferrara, James L.M.

    2001-01-01

    Acute graft-versus-host disease (GVHD) and leukemic relapse remain the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT). Recent studies have demonstrated that the loss of gastrointestinal tract integrity, and specifically the translocation of LPS into the systemic circulation, is critical to the induction of cytokine dysregulation that contributes to GVHD. Using a mouse BMT model, we studied the effects of direct LPS antagonism on GVHD severity and...

  4. Calcitonin gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-κB activation, osteoclastogenesis and bone resorption

    OpenAIRE

    Wang, Liping; Shi, Xiaoyou; Zhao, Rong; Halloran, Bernard P.; Clark, David J; Jacobs, Christopher R; Kingery, Wade S.

    2009-01-01

    Previously we observed that capsaicin treatment in rats inhibited sensory neuropeptide signaling, with a concurrent reduction in trabecular bone formation and bone volume, and an increase in osteoclast numbers and bone resorption. Calcitonin gene-related peptide (CGRP) is a neuropeptide richly distributed in sensory neurons innervating the skeleton and we postulated that CGRP signaling regulates bone integrity. In this study we examined CGRP effects on stromal and bone cell differentiation an...

  5. Bone metabolism during pregnancy.

    Science.gov (United States)

    Salles, Jean Pierre

    2016-06-01

    During pregnancy, mineral concentrations, of calcium and phosphorus in particular, are maintained at a high level in fetal blood so that the developing skeleton may accrete adequate mineral content. The placenta actively transports minerals for this purpose. Maternal intestinal absorption increases in order to meet the fetal demand for calcium, which is only partly dependent on calcitriol. Mineral regulation is essentially dependent on parathyroid hormone (PTH) and PTH-related protein (PTHrP). The calcium-sensing receptor (CaSR) regulates PTH and PTHrP production. If calcium intake is insufficient, the maternal skeleton will undergo resorption due to PTHrP. After birth, a switch from fetal to neonatal homeostasis occurs through increase in PTH and calcitriol, and developmental adaptation of the kidneys and intestines with bone turnover contributing additional mineral to the circulation. Calcium absorption becomes progressively active and dependent on calcitriol. The postnatal skeleton can transiently present with osteoposis but adequate mineral diet usually allows full restoration. Cases of primary osteoporosis must be identified. Loss of trabecular mineral content occurs during lactation in order to provide calcium to the newborn. This programmed bone loss is dependent on a "brain-breast-bone" circuit. The physiological bone resorption during reproduction does not normally cause fractures or persistent osteoporosis. Women who experience fracture are likely to have other causes of bone loss. PMID:27157104

  6. Accidental periapical extrusion of non-setting calcium hydroxide: Unusual bone response and management

    Directory of Open Access Journals (Sweden)

    Divya S Sharma

    2014-01-01

    Full Text Available Premixed non-setting calcium hydroxide is frequently used as interim root canal dressing in endodontically involved permanent teeth and as obturating paste in deciduous teeth in pediatric dentistry. Wide apex in both cases makes it more prone for deliberate extrusion especially when applied with pressure delivery systems. Contrary to common belief the mix was not resorbed in two years with the complaint of insufficiency in mastication. Large mass of calcium hydroxide in bone delayed healing process even after its removal. The present case report intends to demonstrate unusual behavior of bone in response to oily non-setting preparation of calcium hydroxide. Therefore its application with pressure syringe should be reconsidered in pediatric dentistry.

  7. The Pathogenesis of the Bone Disease of Multiple Myeloma

    OpenAIRE

    Edwards, Claire M; Zhuang, Junling; Mundy, Gregory R.

    2008-01-01

    Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. The principal cellular mechanisms involved in the development of myeloma bone disease are an increase in osteoclastic bone resorption, and a reduction in bone formation. Myeloma cells are found in close association with sites of active bone resorption, and the interactions between myeloma cells, and o...

  8. Measurements of fluorine in contemporary urban Canadians: a comparison of the levels found in human bone using in vivo and ex vivo neutron activation analysis

    International Nuclear Information System (INIS)

    Non-invasive in vivo neutron activation analysis (NAA) was used to measure the fluorine concentration in 35 people in Hamilton, Ontario, Canada. Measurement and precision data of this second generation NAA system were determined in 2013, and the results were compared with the performance of a first generation system used in a pilot study of 33 participants from the Hamilton area in 2008. Improvements in precision in line with those predicted by phantom studies were observed, but the use of fewer technicians during measurement seemed adversely to affect performance. We compared the levels of fluorine observed in people between the two studies and found them to be comparable. The average fluorine concentration in bone was found to be 3  ±  0.3 mg and 3.5  ±  0.4 mg F/g Ca for 2013 and 2008 measurements respectively. Ten people were measured in both studies; the observed average change in bone fluorine in this subgroup was consistent with that predicted by the observation of the relationship between bone fluorine and age in the wider group. In addition, we observed differences in the relationship between bone fluorine level and age between men and women, which may be attributable either to sex or gender differences. The rate of increase in fluorine content for men was found to be 0.096  ±  0.022 mg F/g Ca per year while the rate of increase for women was found to be slightly less than half that of men, 0.041  ±  0.017 mg F/g Ca per year. A discontinuity in the rate of increase in fluorine content with age was observed in women at around age 50. Bone fluorine content was significantly lower (p<0.01) in women age 50 to 59 than in women age 40 to 49, which we suggest may be attributable to bone metabolism changes associated with menopause. We also observed increased fluorine levels in tea drinkers as compared to non-tea drinkers, suggesting tea may be a significant source of exposure in Canada. The rate of increase in fluorine content

  9. Activation of β–catenin Signaling in MLO-Y4 Osteocytic Cells versus 2T3 Osteoblastic Cells by Fluid Flow Shear Stress and PGE2: Implications for the Study of Mechanosensation in Bone

    OpenAIRE

    Kamel, Mohamed A; Picconi, Jason L; Lara-Castillo, Nuria; Johnson, Mark L.

    2010-01-01

    The osteocyte is hypothesized to be the mechanosensory cell