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Sample records for decreases bone mobilization

  1. Hyperhomocysteinemia decreases bone blood flow.

    PubMed

    Tyagi, Neetu; Vacek, Thomas P; Fleming, John T; Vacek, Jonathan C; Tyagi, Suresh C

    2011-01-25

    Elevated plasma levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague-Dawley rats were treated with Hcy (0.67 g/L) in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B(12), and folate) were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B(12) levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit) compared with the Hcy-treated group (0.51 ± 0.09). The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.

  2. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

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

    2015-11-01

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

  3. Mushroom Extracts Decrease Bone Resorption and Improve Bone Formation.

    PubMed

    Erjavec, Igor; Brkljacic, Jelena; Vukicevic, Slobodan; Jakopovic, Boris; Jakopovich, Ivan

    2016-01-01

    Mushroom extracts have shown promising effects in the treatment of cancer and various chronic diseases. Osteoporosis is considered one of the most widespread chronic diseases, for which currently available therapies show mixed results. In this research we investigated the in vitro effects of water extracts of the culinary-medicinal mushrooms Trametes versicolor, Grifola frondosa, Lentinus edodes, and Pleurotus ostreatus on a MC3T3-E1 mouse osteoblast-like cell line, primary rat osteoblasts, and primary rat osteoclasts. In an animal osteoporosis model, rats were ovariectomized and then fed 2 mushroom blends of G. frondosa and L. edodes for 42 days. Bone loss was monitored using densitometry (dual-energy X-ray absorptiometry) and micro computed tomography. In the concentration test, mushroom extracts showed no toxic effect on MC3T3-E1 cells; a dose of 24 µg/mL showed the most proliferative effect. Mushroom extracts of T. versicolor, G. frondosa, and L. edodes inhibited osteoclast activity, whereas the extract of L. edodes increased osteoblast mineralization and the production of osteocalcin, a specific osteoblastic marker. In animals, mushroom extracts did not prevent trabecular bone loss in the long bones. However, we show for the first time that the treatment with a combination of extracts from L. edodes and G. frondosa significantly reduced trabecular bone loss at the lumbar spine. Inhibitory properties of extracts from L. edodes on osteoclasts and the promotion of osteoblasts in vitro, together with the potential to decrease lumbar spine bone loss in an animal osteoporosis model, indicate that medicinal mushroom extracts can be considered as a preventive treatment and/or a supplement to pharmacotherapy to enhance its effectiveness and ameliorate its harmful side effects.

  4. Decreased hematopoietic progenitor cell mobilization in pearl mice.

    PubMed

    Vallejo, Matthew O; Niemeyer, Glenn P; Vaglenov, Alex; Hock, Tommy; Urie, Bridget; Christopherson, Peter; Lothrop, Clinton D

    2013-10-01

    Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) assay, bone marrow lineage negative (lin(-)), Sca(+) and c-kit(+) cells (LSK cells), bone marrow elastase, myeloperoxidase, and cathepsin G enzyme activity were compared in C57Bl6 (Bl/6) and pearl mice. Stress granulopoiesis was evaluated following 200 mg/kg cyclophosphamide or 1 mg/kg bortezomib administration and by limiting dilution bone marrow transplantation. The CBCs and CFUs were determined in Bl/6 and pearl mice following AMD3100 or granulocyte colony-stimulating factor (G-CSF) administration. Pearl mice were not neutropenic and did not have cyclic neutropenia. Bone marrow elastase, myeloperoxidase, and cathepsin G enzyme activity were similar in pearl and Bl/6 mice. The numbers of CFU-G, CFU-GEMM, and LSK cells were increased moderately in pearl mice. Stress granulopoiesis was similar in Bl/6 and pearl mice. CFU assays and CBCs performed on Bl/6 and pearl mice administered AMD3100 resulted in similar results. However, normal mice administered G-CSF had higher peripheral blood neutrophil counts and greater CFU numbers compared with pearl mice. Unlike patients with HPS-2 and dogs with CH, pearl mice did not have neutropenia or CH but had decreased hematopoietic progenitor cell and granulocyte mobilization in response to G-CSF. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  5. Evidence that a lipolytic enzyme--hematopoietic-specific phospholipase C-β2--promotes mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention and increasing the promobilizing effects of granulocytes.

    PubMed

    Adamiak, M; Poniewierska-Baran, A; Borkowska, S; Schneider, G; Abdelbaset-Ismail, A; Suszynska, M; Abdel-Latif, A; Kucia, M; Ratajczak, J; Ratajczak, M Z

    2016-04-01

    Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an important role in mobilizing HSPCs into the peripheral blood (PB) by (i) inducing degranulation of BM-residing granulocytes and (ii) promoting their egress from the BM into the PB so that they permeabilize the endothelial barrier for subsequent egress of HSPCs. We report here that hematopoietic cell-specific phospholipase C-β2 (PLC-β2) has a crucial role in pharmacological mobilization of HSPCs. On the one hand, when released during degranulation of granulocytes, it digests GPI-A, thereby disrupting membrane lipid rafts and impairing retention of HSPCs in BM niches. On the other hand, it is an intracellular enzyme required for degranulation of granulocytes and their egress from BM. In support of this dual role, we demonstrate that PLC-β2-knockout mice are poor mobilizers and provide, for the first time, evidence for the involvement of this lipolytic enzyme in the mobilization of HSPCs.

  6. Evidence that a lipolytic enzyme—hematopoietic-specific phospholipase C-β2—promotes mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention and increasing the promobilizing effects of granulocytes

    PubMed Central

    Adamiak, M; Poniewierska-Baran, A; Borkowska, S; Schneider, G; Abdelbaset-Ismail, A; Suszynska, M; Abdel-Latif, A; Kucia, M; Ratajczak, J; Ratajczak, M Z

    2016-01-01

    Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an important role in mobilizing HSPCs into the peripheral blood (PB) by (i) inducing degranulation of BM-residing granulocytes and (ii) promoting their egress from the BM into the PB so that they permeabilize the endothelial barrier for subsequent egress of HSPCs. We report here that hematopoietic cell-specific phospholipase C-β2 (PLC-β2) has a crucial role in pharmacological mobilization of HSPCs. On the one hand, when released during degranulation of granulocytes, it digests GPI-A, thereby disrupting membrane lipid rafts and impairing retention of HSPCs in BM niches. On the other hand, it is an intracellular enzyme required for degranulation of granulocytes and their egress from BM. In support of this dual role, we demonstrate that PLC-β2-knockout mice are poor mobilizers and provide, for the first time, evidence for the involvement of this lipolytic enzyme in the mobilization of HSPCs. PMID:26582648

  7. Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.

    PubMed Central

    Kimble, R B; Vannice, J L; Bloedow, D C; Thompson, R C; Hopfer, W; Kung, V T; Brownfield, C; Pacifici, R

    1994-01-01

    Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and bone cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because of its potent stimulatory effects on bone resorption in vitro and in vivo. To investigate whether IL-1 plays a direct causal role in post ovariectomy bone loss, 6-mo-old ovariectomized rats were treated with subcutaneous infusions of IL-1 receptor antagonist (IL-1ra), a specific competitor of IL-1, for 4 wk, beginning either at the time of surgery or 4 wk after ovariectomy. The bone density of the distal femur was measured non invasively by dual-energy X-ray absorptiometry. Bone turnover was assessed by bone histomorphometry and by measuring serum osteocalcin, a marker of bone formation, and the urinary excretion of pyridinoline cross-links, a marker of bone resorption. Ovariectomy caused a rapid increase in bone turnover and a marked decrease in bone density which were blocked by treatment with 17 beta estradiol. Ovariectomy also increased the production of IL-1 from cultured bone marrow cells. Ovariectomy induced-bone loss was significantly decreased by IL-1ra treatment started at the time of ovariectomy and completely blocked by IL-1ra treatment begun 4 wk after ovariectomy. In both studies IL-1ra also decreased bone resorption in a manner similar to estrogen, while it had no effect on bone formation. In contrast, treatment with IL-1ra had no effect on the bone density and the bone turnover of sham-operated rats, indicating that IL-1ra specifically blocked estrogen-dependent bone loss. In conclusion, these data indicate that IL-1, or mediators induced by IL-1, play an important causal role in the mechanism by which ovariectomy induces bone loss in rats, especially following the immediate post ovariectomy period. Images PMID:8182127

  8. Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

    2002-01-01

    The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

  9. Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

    NASA Technical Reports Server (NTRS)

    Bloomfield, Susan A.; Hogan, Harry A.; Delp, Michael D.

    2002-01-01

    The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

  10. Dopamine regulates endothelial progenitor cell mobilization from mouse bone marrow in tumor vascularization.

    PubMed

    Chakroborty, Debanjan; Chowdhury, Uttio Roy; Sarkar, Chandrani; Baral, Rathindranath; Dasgupta, Partha Sarathi; Basu, Sujit

    2008-04-01

    Mobilization of endothelial progenitor cells (EPCs) from the bone marrow and their subsequent participation in neovessel formation are implicated in tumor growth and neovascularization. As the neurotransmitter dopamine (DA) modulates adult endothelial cell function, we hypothesized that DA might have a regulatory role in mobilization of EPCs from the bone marrow niche. We show that there was a significant decrease in bone marrow DA content and an increase in EPC mobilization in tumor-bearing mice associated with tumor neovascularization. DA treatment of tumor-bearing mice inhibited EPC mobilization and tumor growth through its D2 receptors, as DA treatment failed to inhibit EPC mobilization in tumor-bearing mice treated with a specific DA D2 receptor antagonist and in tumor-bearing mice lacking the D2 receptor. In addition, we found that DA, through D2 receptors, exerted its inhibitory effect on EPC mobilization through suppression of VEGFA-induced ERK1/ERK2 phosphorylation and MMP-9 synthesis. These findings reveal a new link between DA and EPC mobilization and suggest a novel use for DA and D2 agents in the treatment of cancer and other diseases involving neovessel formation.

  11. A short-term zinc-deficient diet decreases bone formation through down-regulated BMP2 in rat bone.

    PubMed

    Suzuki, Takako; Katsumata, Shin-Ichi; Matsuzaki, Hiroshi; Suzuki, Kazuharu

    2016-07-01

    We investigated the effects of a short-term dietary zinc deficiency on bone metabolism. Zinc deficiency increased the mRNA expression of zinc uptake transporters such as Zip1, Zip13, and Zip14 in bone. However, zinc deficiency might not maintain zinc storage in bone, resulting in a decrease in bone formation through downregulation of the expression levels of osteoblastogenesis-related genes.

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

    PubMed

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

    2016-09-01

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

  13. Decreased Estrogen May Contribute to Osteopenia in Unloaded Bones

    NASA Technical Reports Server (NTRS)

    Tou, Janet; Arnaud, Sara; Grindeland, Richard; Wade, Charles

    2004-01-01

    Progressive loss of weight-bearing bone in astronauts is one of the most serious impediments to long-duration spaceflight. Estrogen deficiency in women is an established factor in bone loss. Reduced sex hormone levels have been reported in male astronauts, but no data is available regarding spaceflight effects on female sex hormones. The objective of our study was to determine the role of estrogen in disuse osteopenia. The NASA developed hindlimb suspension (HLS) model was used to simulate the unloading disuse of weight-bearing bones experienced in space. Female Sprague-Dawley rats (age 77d; n = 20/group) were HLS or kept ambulatory (AMB) for 38 d and endocrine and bone indices determined. HLS of rats resulted in lower (p less than 0.01) bone mass (9%0), bone mineral content (BMC 13%) and mechanical strength (28%) compared to AMB animals. Plasma estradiol (E2) was lower (p = 0.03) in HLS (10.1 +/- 1.4 pg/ml) compared to AMB rats (16.7 +/- 2.6 pg/ml). E2 was positively correlated to BMC r(sup 2) = 0.67 and mechanical strength r(sup 2) = 0.61. These results suggest that reduced E2 plays a role in disuse osteopenia induced by HLS. Plasma or pituitary lutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were not different in HLS versus AMB rats. However, pituitary LH was correlated to E2 (r(sup 2) = 0.57), suggesting changes in E2 were exerted at the level of the hypothalamus-pituitary axis. Understanding the role of estrogen in disuse osteopenia is necessary to the development of efficacious therapies for female astronauts, bed rest patients and the increasing number of individuals in our sedentary population suffering bone loss.

  14. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect.

    PubMed

    Kumar, Sanjay; Ponnazhagan, Selvarangan

    2012-04-01

    Although the number of mesenchymal stem cells (MSC) in the bone marrow is sufficient to maintain skeletal homeostasis, in osteopenic pathology, aggravated osteoclast activity or insufficient osteoblast numbers ensue, affecting normal bone remodeling. Most of the currently available therapies are anti-resorptive with limited osteogenic potential. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in tissue repair, amplification of endogenous stem cells may provide an alternative approach in these conditions. The present study determined the potential of MSC mobilization in vivo, using combinations of different growth factors with the CXCR4 antagonist, AMD3100, in a mouse model of segmental bone defect. Results indicated that among several factors tested IGF1 had maximum proliferative ability of MSC in vitro. Results of the in vivo studies indicated that the combination of IGF1 and AMD3100 provided significant augmentation of bone growth as determined by DXA, micro-CT and histomorphometry in mice bearing segmental fractures. Further, characterization of MSC isolated from mice treated with IGF1 and AMD3100 indicated Akt/PI3K, MEK1/2-Erk1/2 and smad2/3 as key signaling pathways mediating this effect. These data indicate the potential of in vivo stem cell mobilization as a novel alternative for bone healing.

  15. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs.

    PubMed

    Winkler, Ingrid G; Sims, Natalie A; Pettit, Allison R; Barbier, Valérie; Nowlan, Bianca; Helwani, Falak; Poulton, Ingrid J; van Rooijen, Nico; Alexander, Kylie A; Raggatt, Liza J; Lévesque, Jean-Pierre

    2010-12-02

    In the bone marrow, hematopoietic stem cells (HSCs) reside in specific niches near osteoblast-lineage cells at the endosteum. To investigate the regulation of these endosteal niches, we studied the mobilization of HSCs into the bloodstream in response to granulocyte colony-stimulating factor (G-CSF). We report that G-CSF mobilization rapidly depletes endosteal osteoblasts, leading to suppressed endosteal bone formation and decreased expression of factors required for HSC retention and self-renewal. Importantly, G-CSF administration also depleted a population of trophic endosteal macrophages (osteomacs) that support osteoblast function. Osteomac loss, osteoblast suppression, and HSC mobilization occurred concomitantly, suggesting that osteomac loss could disrupt endosteal niches. Indeed, in vivo depletion of macrophages, in either macrophage Fas-induced apoptosis (Mafia) transgenic mice or by administration of clodronate-loaded liposomes to wild-type mice, recapitulated the: (1) loss of endosteal osteoblasts and (2) marked reduction of HSC-trophic cytokines at the endosteum, with (3) HSC mobilization into the blood, as observed during G-CSF administration. Together, these results establish that bone marrow macrophages are pivotal to maintain the endosteal HSC niche and that the loss of such macrophages leads to the egress of HSCs into the blood.

  16. Low bone mineral density and decreased bone turnover in Duchenne muscular dystrophy.

    PubMed

    Söderpalm, Ann-Charlott; Magnusson, Per; Ahlander, Anne-Christine; Karlsson, Jón; Kroksmark, Anna-Karin; Tulinius, Már; Swolin-Eide, Diana

    2007-12-01

    This cross-sectional study examined bone mineral density, bone turnover, body composition and calciotropic hormones in 24 boys with Duchenne muscular dystrophy (DMD) (2.3-19.7 years), most of whom were being treated with prednisolone, and 24 age-matched healthy boys. Our study demonstrated lower bone mineral density in the DMD group for total body, spine, hip, heel and forearm measurements. These differences between DMD patients and controls increased with increasing age. Biochemical markers of both bone formation and resorption revealed reduced bone turnover in DMD patients. The fracture rate was not higher in DMD patients. The DMD group had low vitamin D levels but high leptin levels in comparison with the control group. Muscle strength correlated with bone mineral density assessed at the hip and heel in the DMD group. Interventions that increase bone formation should be considered, as DMD patients have reduced bone turnover in addition to their low bone mineral density.

  17. Diet-induced Obesity Alters Bone Remodeling Leading to Decreased Femoral Trabecular Bone Mass in Mice

    USDA-ARS?s Scientific Manuscript database

    Body mass derived from an obesity condition may be detrimental to bone health but the mechanism is unknown. This study was to examine changes in bone structure and serum cytokines related to bone metabolism in obese mice induced by a high-fat diet(HFD). Mice fed the HFD were obese and had higher ser...

  18. Low bone mineral mass is associated with decreased bone formation and diet in girls with Rett syndrome.

    PubMed

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

    2014-09-01

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

  19. Effect of cadmium on osteogenesis within diffusion chambers by bone marrow cells: biochemical evidence of decreased bone formation capacity.

    PubMed

    Dohi, Y; Sugimoto, K; Yoshikawa, T; Ohgushi, H; Katsuda, T; Tabata, S; Moriyama, T

    1993-06-01

    The biological and biochemical effects of cadmium administration on bone marrow in rats were examined. When young adult rats were administered cadmium (Cd) repeatedly at a dose of 750 micrograms/kg body wt for up to 4 weeks, metallothionein mRNA was detected by a gene expression analysis in their bone marrow at 2 weeks after the first Cd administration, though the amounts were lower than those in liver. To determine the direct effect of cadmium on bone formation, the potential of Cd-treated bone marrow cells and demineralized bone matrix (DBM) to form bone and cartilage was assessed using a diffusion chamber (DC) in vivo, by histological examination, and by biochemical parameters such as alkaline phosphatase (ALP) activity, total calcium and phosphorus content, and the bone-specific vitamin K-dependent Gla-containing protein (BGP) content, relative to mineralization. Diffusion chambers were inoculated with DBM and bone marrow cells from either Cd-treated or nontreated rats (control) and were then implanted subcutaneously into syngeneic nontreated rats. The accumulation of BGP in DCs with Cd-treated bone marrow was significantly lower than that in control DCs. Unlike in control DC, a peak of ALP activity did not occur at 4 weeks postimplantation in DC implants inoculated with Cd-treated bone marrow; the ALP activity and calcium content in these implants were also significantly lower than those of the control bone marrow-containing chambers at the early stage of implantation. Histological examinations of chambers with Cd-treated marrow showed a decreased area of cartilage and bone foci compared with those in control chambers. These findings suggest that Cd administration inhibits the osteoblastic and chondroblastic differentiation pathway in bone marrow through direct effects on these cells.

  20. Bone marrow adsorbed dose of rhenium-186-HEDP and the relationship with decreased platelet counts

    SciTech Connect

    Klerk, J.M.H. de; Dieren, E.B. van; Schip, A.D. van het

    1996-01-01

    Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP) has been used for palliation of metastatic bone pain. The purpose of this study was to find a relationship between the bone marrow absorbed dose and the toxicity, expressed as the percentage decrease in the peripheral blood platelet count. The bone marrow absorbed dose was calculated according to the MIRD model using data obtained from ten treatments of patients suffering from metastatic prostate cancer; noninvasive and pharmacokinetic method were used. The bone marrow doses were related to toxicity using the pharmacodynamic sigmoid E{sub max} model. The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq, respectively). There was a good relationship between the toxicity and the bone marrow absorbed dose (r = 0.80). Furthermore, the EDrm{sub 50} (i.e., the bone marrow absorbed dose producing a 50% platelet decrease) to bone marrow for {sup 186}Re-HEDP was on the order of 2 Gy. Although the function of normal bone marrow is affected by metastases in patients with metastatic bone disease, the MIRD model can be used to relate toxicity to the bone marrow absorbed dose after a therapeutic dosage of {sup 186}Re-HEDP. 33 refs., 1 fig., 1 tab.

  1. Effects of Decreased Occlusal Loading during Growth on the Mandibular Bone Characteristics

    PubMed Central

    Hichijo, Natsuko; Tanaka, Eiji; Kawai, Nobuhiko; van Ruijven, Leo J.; Langenbach, Geerling E. J.

    2015-01-01

    Background Bone mass and mineralization are largely influenced by loading. The purpose of this study was to evaluate the reaction of the entire mandibular bone in response to decreased load during growth. It is hypothesized that decreased muscular loading will lead to bone changes as seen during disuse, i.e. loss of bone mass. Methods and Findings Ten 21-day-old Wistar strain male rats were divided into two groups (each n=5) and fed on either a hard- or soft-diet for 11 weeks. Micro-computed tomography was used for the investigation of bone mineralization, bone volume, bone volume fraction (BV/TV) and morphological analysis. Mandibular mineralization patterns were very consistent, showing a lower degree of mineralization in the ramus than in the corpus. In the soft-diet group, mineralization below the molars was significantly increased (p<0.05) compared to the hard diet group. Also, bone volume and BV/TV of the condyle and the masseter attachment were decreased in the soft-diet group (p<0.05). Morphological analysis showed inhibited growth of the ramus in the soft-diet group (p<0.05). Conclusion Decreased loading by a soft diet causes significant changes in the mandible. However, these changes are very region-specific, probably depending on the alterations in the local loading regime. The results suggest that muscle activity during growth is very important for bone quality and morphology. PMID:26062027

  2. Ubiquitin C-terminal hydrolase L1 deficiency decreases bone mineralization.

    PubMed

    Shim, Sehwan; Kwon, Young-Bae; Yoshikawa, Yasuhiro; Kwon, Jungkee

    2008-06-01

    Ubiquitin C-terminal hydrolase L1 is a component of the ubiquitin proteasome system, which evidences unique biological activities. In this study, we report the pattern of UCH-L1 expression, and show that it regulates bone mineralization in osteogenesis. UCH-L1 was expressed in osteoblasts, osteoclasts, and hematopoietic precursor cells of bone marrow in the metaphysis and diaphysis of the femora. To further assess the involvement of UCH-L1 in the regulation of bone mineralization, we evaluated the bone mineral density (BMD) rate of gad mice, using the Latheta computed tomography system. Male gad mice evidenced a significantly decreased BMD rate in the metaphysis and diaphysis of the femora. These findings of decreased BMD rate in the bones of gad mice may suggest that UCH-L1 function regulates bone mineralization during osteogenesis.

  3. Homocysteine mediated decrease in bone blood flow and remodeling: Role of Folic Acid

    PubMed Central

    Tyagi, Neetu; Kandel, Madhavi; Munjal, Charu; Vacek, Jonathan C.; Qipshidze, Natia; SB, Pushpakumar; Metreveli, Naria; Tyagi, Suresh C.

    2013-01-01

    Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, homocysteine (Hcy) accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid in genetically HHcy associated decrease in bone blood flow and remodeling. Wildtype (WT) and cystathionine-β-synthase heterozygous (CBS+/−) mice were used in this study and supplemented with or without folic acid (FA 300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density was assessed by dual energy X-ray absorptiometry. The bone homogenates were analyzed for oxidative stress,NOX-4 as oxidative marker and thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/− mice. The bone density was also reduced in CBS+/− mice. There was an increase in NOX-4, iNOS, MMP -9 protein as well as MMP-9 activity in CBS+/− mice and decrease in Trx-1, eNOS protein levels, in part by decreasing NO bio-availability in CBS+/− mice. Interestingly, these effects were ameliorated by folic acid and suggested that folic acid supplementation may have therapeutic potential against genetically HHcy induced bone loss. PMID:21469179

  4. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass☆,☆☆

    PubMed Central

    Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O. C.; Chun, Jerold; Salles, Jean Pierre

    2013-01-01

    Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1–LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1(−/−) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1(−/−) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1(−/−) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology. PMID:21569876

  5. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass.

    PubMed

    Gennero, Isabelle; Laurencin-Dalicieux, Sara; Conte-Auriol, Françoise; Briand-Mésange, Fabienne; Laurencin, Danielle; Rue, Jackie; Beton, Nicolas; Malet, Nicole; Mus, Marianne; Tokumura, Akira; Bourin, Philippe; Vico, Laurence; Brunel, Gérard; Oreffo, Richard O C; Chun, Jerold; Salles, Jean Pierre

    2011-09-01

    Lysophosphatidic acid (LPA) is a lipid mediator that acts in paracrine systems via interaction with a subset of G protein-coupled receptors (GPCRs). LPA promotes cell growth and differentiation, and has been shown to be implicated in a variety of developmental and pathophysiological processes. At least 6 LPA GPCRs have been identified to date: LPA1-LPA6. Several studies have suggested that local production of LPA by tissues and cells contributes to paracrine regulation, and a complex interplay between LPA and its receptors, LPA1 and LPA4, is believed to be involved in the regulation of bone cell activity. In particular, LPA1 may activate both osteoblasts and osteoclasts. However, its role has not as yet been examined with regard to the overall status of bone in vivo. We attempted to clarify this role by defining the bone phenotype of LPA1((-/-)) mice. These mice demonstrated significant bone defects and low bone mass, indicating that LPA1 plays an important role in osteogenesis. The LPA1((-/-)) mice also presented growth and sternal and costal abnormalities, which highlights the specific roles of LPA1 during bone development. Microcomputed tomography and histological analysis demonstrated osteoporosis in the trabecular and cortical bone of LPA1((-/-)) mice. Finally, bone marrow mesenchymal progenitors from these mice displayed decreased osteoblastic differentiation. These results suggest that LPA1 strongly influences bone development both qualitatively and quantitatively and that, in vivo, its absence results in decreased osteogenesis with no clear modification of osteoclasis. They open perspectives for a better understanding of the role of the LPA/LPA1 paracrine pathway in bone pathophysiology. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Decreased Bone Volume and Bone Mineral Density in the Tibial Trabecular Bone Is Associated with Per2 Gene by 405 nm Laser Stimulation.

    PubMed

    Yoo, Yeong-Min; Lee, Myung-Han; Park, Ji Hyung; Seo, Dong-Hyun; Lee, Sangyeob; Jung, Byungjo; Kim, Han Sung; Bae, Kiho

    2015-11-16

    Low-level laser therapy/treatment (LLLT) using a minimally invasive laser needle system (MILNS) might enhance bone formation and suppress bone resorption. In this study, the use of 405 nm LLLT led to decreases in bone volume and bone mineral density (BMD) of tibial trabecular bone in wild-type (WT) and Per2 knockout (KO) mice. Bone volume and bone mineral density of tibial trabecular bone was decreased by 405 nm LLLT in Per2 KO compared to WT mice at two and four weeks. To determine the reduction in tibial bone, mRNA expressions of alkaline phosphatase (ALP) and Per2 were investigated at four weeks after 405 nm laser stimulation using MILNS. ALP gene expression was significantly reduced in the LLLT-stimulated right tibial bone of WT and Per2 KO mice compared to the non-irradiated left tibia (p < 0.001). Per2 mRNA expression in WT mice was significantly reduced in the LLLT-stimulated right tibial bone compared to the non-irradiated left tibia (p < 0.001). To identify the decrease in tibial bone mediated by the Per2 gene, levels of runt-related transcription factor 2 (Runx2) and ALP mRNAs were determined in non-irradiated WT and Per2 KO mice. These results demonstrated significant downregulation of Runx2 and ALP mRNA levels in Per2 KO mice (p < 0.001). Therefore, the reduction in tibial trabecular bone resulting from 405 nm LLLT using MILNS might be associated with Per2 gene expression.

  7. Decreased Bone Volume and Bone Mineral Density in the Tibial Trabecular Bone Is Associated with Per2 Gene by 405 nm Laser Stimulation

    PubMed Central

    Yoo, Yeong-Min; Lee, Myung-Han; Park, Ji Hyung; Seo, Dong-Hyun; Lee, Sangyeob; Jung, Byungjo; Kim, Han Sung; Bae, Kiho

    2015-01-01

    Low-level laser therapy/treatment (LLLT) using a minimally invasive laser needle system (MILNS) might enhance bone formation and suppress bone resorption. In this study, the use of 405 nm LLLT led to decreases in bone volume and bone mineral density (BMD) of tibial trabecular bone in wild-type (WT) and Per2 knockout (KO) mice. Bone volume and bone mineral density of tibial trabecular bone was decreased by 405 nm LLLT in Per2 KO compared to WT mice at two and four weeks. To determine the reduction in tibial bone, mRNA expressions of alkaline phosphatase (ALP) and Per2 were investigated at four weeks after 405 nm laser stimulation using MILNS. ALP gene expression was significantly reduced in the LLLT-stimulated right tibial bone of WT and Per2 KO mice compared to the non-irradiated left tibia (p < 0.001). Per2 mRNA expression in WT mice was significantly reduced in the LLLT-stimulated right tibial bone compared to the non-irradiated left tibia (p < 0.001). To identify the decrease in tibial bone mediated by the Per2 gene, levels of runt-related transcription factor 2 (Runx2) and ALP mRNAs were determined in non-irradiated WT and Per2 KO mice. These results demonstrated significant downregulation of Runx2 and ALP mRNA levels in Per2 KO mice (p < 0.001). Therefore, the reduction in tibial trabecular bone resulting from 405 nm LLLT using MILNS might be associated with Per2 gene expression. PMID:26580614

  8. Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid.

    PubMed

    Tyagi, Neetu; Kandel, Madhavi; Munjal, Charu; Qipshidze, Natia; Vacek, Jonathan C; Pushpakumar, Sathnur B; Metreveli, Naria; Tyagi, Suresh C

    2011-10-01

    Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, Hcy accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid (FA) in genetically HHcy-associated decrease in bone blood flow and remodeling. Wild type (WT) and cystathionine-β-synthase heterozygous (CBS+/-) mice were used in this study and supplemented with or without FA (300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density (BD) was assessed by dual energy X-ray absorptiometry. The bone homogenates were analyzed for oxidative stress, NOX-4 as oxidative marker and thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/- mice. The BD was also reduced in CBS+/- mice. There was an increase in NOX-4, iNOS, MMP-9 protein as well as MMP-9 activity in CBS+/- mice and decrease in Trx-1, eNOS protein levels, in part by decreasing NO bio-availability in CBS+/- mice. Interestingly, these effects were ameliorated by FA and suggested that FA supplementation may have therapeutic potential against genetically HHcy induced bone loss.

  9. Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle.

    PubMed

    Giesen, E B W; Ding, M; Dalstra, M; van Eijden, T M G J

    2003-05-01

    To investigate the influence of decreased mechanical loading on the density and mechanical properties of the cancellous bone of the human mandibular condyle. Destructive compressive mechanical tests were performed on cancellous bone specimens.Background. Reduced masticatory function in edentate people leads to a reduction of forces acting on the mandible. As bone reacts to its mechanical environment a change in its material properties can be expected. Cylindrical bone specimens were obtained from dentate and edentate embalmed cadavers. Mechanical parameters were determined in the axial and in the transverse directions. Subsequently, density parameters were determined according to a method based on Archimedes' principle. The apparent density and volume fraction of the bone were about 18% lower in the edentate group; no age-related effect on density was found. The decrease of bone in the edentate group was associated with a lower stiffness and strength (about 22% and 28%, respectively). The ultimate strain, however, did not differ between the two groups. Both groups had similar mechanical anisotropy; in axial loading the bone was stiffer and stronger than in transverse loading. Reduced mechanical load had affected the density and herewith the mechanical properties of condylar cancellous bone, but not its anisotropy. The change in material properties of the cancellous bone after loss of teeth indicate that the mandibular condyle is sensitive for changes in its mechanical environment. Therefore, changes in mechanical loading of the condyle have to be accounted for in surgical procedures of the mandible.

  10. ADAR1 ablation decreases bone mass by impairing osteoblast function in mice.

    PubMed

    Yu, Shibing; Sharma, Rohit; Nie, Daibang; Jiao, Hongli; Im, Hee-Jeong; Lai, Yumei; Zhao, Zhongfang; Zhu, Ke; Fan, Jie; Chen, Di; Wang, Qingde; Xiao, Guozhi

    2013-01-15

    Bone mass is controlled through a delicate balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. We show here that RNA editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) is critical for proper control of bone mass. Postnatal conditional knockout of Adar1 (the gene encoding ADAR1) resulted in a severe osteopenic phenotype. Ablation of the Adar1 gene significantly suppressed osteoblast differentiation without affecting osteoclast differentiation in bone. In vitro deletion of the Adar1 gene decreased expression of osteoblast-specific osteocalcin and bone sialoprotein genes, alkaline phosphatase activity, and mineralization, suggesting a direct intrinsic role of ADAR1 in osteoblasts. ADAR1 regulates osteoblast differentiation by, at least in part, modulation of osterix expression, which is essential for bone formation. Further, ablation of the Adar1 gene decreased the proliferation and survival of bone marrow stromal cells and inhibited the differentiation of mesenchymal stem cells towards osteoblast lineage. Finally, shRNA knockdown of the Adar1 gene in MC-4 pre-osteoblasts reduced cyclin D1 and cyclin A1 expression and cell growth. Our results identify ADAR1 as a new key regulator of bone mass and suggest that ADAR1 functions in this process mainly through modulation of the intrinsic properties of osteoblasts (i.e., proliferation, survival and differentiation).

  11. Demonstration of skull bones mobility using optical methods: practical importance in medicine

    NASA Astrophysics Data System (ADS)

    Zakharov, Alexander V.; Okushko, Vladimir R.; Vturin, Sergey A.; Moseychuk, Vladimir V.; Petrov, Aleksey A.; Suetenkov, Dmitry E.

    2014-01-01

    Unprompted skull bones mobility not related to breathing, heart beating and other physiological reactions, using installation of original construction with control of physiological parameters by biofeedback hardware-software complex BOS-lab and BOS-pulse appliance (COMSIB, Novosibirsk, Russia) has been confirmed. Teeth eruption occurs through odontiasis canals, emerging from the funiculus. The main driving force for promoting a tooth into odontiasis canal during eruption is the unprompted skull bones mobility. A simple optical installation was made for the visualization of skull bones mobility during the investigation of the median palatine and incisors sutures. Early detection of failures of unprompted skull bones mobility and its normalization can lead to prevention of impact teeth, malocclusion, extrudocclusion and other anomalies and deformations of teeth, teeth rows, TMJ and skull. The skull bones mobility should be considered during the early preventive treatment and therapy of the consequences of injuries and malfunction of the maxillofacial area.

  12. Tail-suspended mice lacking calponin H1 experience decreased bone loss.

    PubMed

    Yotsumoto, Naoki; Takeoka, Michiko; Yokoyama, Minesuke

    2010-07-01

    Calponin h1 (CNh1) is an actin-binding protein originally isolated from vascular smooth muscle and has been reported to suppress bone formation. We are therefore curious how CNh1 is involved in bone loss that is caused by space flight in microgravity. We assessed the effects of tail suspension (TS) in C57BL/6J wild (CN+/+) and CNh1-deleted (CN-/-) mice to elucidate the role of CNh1 in bone loss under weightless conditions. Bone mineral density (BMD) of tibiae was measured by single energy X-ray absorptiometry, and bone volume fraction (BV/TV), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured by bone histomorphometry. BMD, BV/TV, MAR, and BFR/BS were lower in CN+/+ mice with TS than in those without. In the CN-/- group, however, the decrease in each of these parameters by TS was ameliorated. Decreases in serum osteocalcin levels by TS in CN+/+ mice were attenuated in CN-/- mice. Furthermore, urinary deoxypyridinolin (DPD), an indicator of bone resorption, was increased in CN+/+ mice following TS, but not in CN-/- mice. In transfection experiments, the degree of induction of bone formation markers, alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)-4 mRNA expression, under stimulation with BMP-2, was lower in MC3T3-E1 mouse osteoblast-like cells expressing CNh1 than that in mock transfected cells. Notably, the BMP-2-induced ALP activity was decreased by CNh1 expression, which was partially rescued by treatment with the Rho kinase inhibitor Y27632. Taken together, these results indicate that CNh1 is responsible for weightlessness-induced bone loss in part through Rho signaling pathway.

  13. Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss

    PubMed Central

    Doyard, Mathilde; Chappard, Daniel; Leroyer, Patricia; Roth, Marie-Paule; Loréal, Olivier; Guggenbuhl, Pascal

    2016-01-01

    Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe−/− male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe−/− animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe−/− mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski’s fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis. PMID:26829642

  14. Chinese preparation Xuesaitong promotes the mobilization of bone marrow mesenchymal stem cells in rats with cerebral infarction.

    PubMed

    Zhang, Jin-Sheng; Zhang, Bao-Xia; Du, Mei-Mei; Wang, Xiao-Ya; Li, Wei

    2016-02-01

    After cerebral ischemia, bone marrow mesenchymal stem cells are mobilized and travel from the bone marrow through peripheral circulation to the focal point of ischemia to initiate tissue regeneration. However, the number of bone marrow mesenchymal stem cells mobilized into peripheral circulation is not enough to exert therapeutic effects, and the method by which blood circulation is promoted to remove blood stasis influences stem cell homing. The main ingredient of Xuesaitong capsules is Panax notoginseng saponins, and Xuesaitong is one of the main drugs used for promoting blood circulation and removing blood stasis. We established rat models of cerebral infarction by occlusion of the middle cerebral artery and then intragastrically administered Xuesaitong capsules (20, 40 and 60 mg/kg per day) for 28 successive days. Enzyme-linked immunosorbent assay showed that in rats with cerebral infarction, middle- and high-dose Xuesaitong significantly increased the level of stem cell factors and the number of CD117-positive cells in plasma and bone marrow and significantly decreased the number of CD54- and CD106-positive cells in plasma and bone marrow. The effect of low-dose Xuesaitong on these factors was not obvious. These findings demonstrate that middle- and high-dose Xuesaitong and hence Panax notoginseng saponins promote and increase the level and mobilization of bone marrow mesenchymal stem cells in peripheral blood.

  15. Fracture induced mobilization and incorporation of bone marrow-derived endothelial progenitor cells for bone healing.

    PubMed

    Matsumoto, Tomoyuki; Mifune, Yutaka; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Shoji, Taro; Iwasaki, Hiroto; Suzuki, Takahiro; Oyamada, Akira; Horii, Miki; Yokoyama, Ayumi; Nishimura, Hiromi; Lee, Sang Yang; Miwa, Masahiko; Doita, Minoru; Kurosaka, Masahiro; Asahara, Takayuki

    2008-04-01

    We recently reported that systemic administration of peripheral blood (PB) CD34+ cells, an endothelial progenitor cell (EPC)-enriched population, contributed to fracture healing via vasculogenesis/angiogenesis. However, pathophysiological role of EPCs in fracture healing process has not been fully clarified. Therefore, we investigated the hypothesis whether mobilization and incorporation of bone marrow (BM)-derived EPCs may play a pivotal role in appropriate fracture healing. Serial examinations of Laser doppler perfusion imaging and histological capillary density revealed that neovascularization activity at the fracture site peaked at day 7 post-fracture, the early phase of endochondral ossifification. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the frequency of BM cKit+Sca1+Lineage- (Lin-) cells and PB Sca1+Lin- cells, which are EPC-enriched fractions, significantly increased post-fracture. The Sca1+ EPC-derived vasuculogenesis at the fracture site was confirmed by double immunohistochemistry for CD31 and Sca1. BM transplantation from transgenic donors expressing LacZ transcriptionally regulated by endothelial cell-specific Tie-2 promoter into wild type also provided direct evidence that EPCs contributing to enhanced neovascularization at the fracture site were specifically derived from BM. Animal model of systemic administration of PB Sca1+Lin- Green Fluorescent Protein (GFP)+ cells further confirmed incorporation of the mobilized EPCs into the fracture site for fracture healing. These findings indicate that fracture may induce mobilization of EPCs from BM to PB and recruitment of the mobilized EPCs into fracture sites, thereby augment neovascularization during the process of bone healing. EPCs may play an essential role in fracture healing by promoting a favorable environment through neovascularization in damaged skeletal tissue.

  16. Adult stem cell mobilization enhances intramembranous bone regeneration: a pilot study.

    PubMed

    McNulty, Margaret A; Virdi, Amarjit S; Christopherson, Kent W; Sena, Kotaro; Frank, Robin R; Sumner, Dale R

    2012-09-01

    Stem cell mobilization, which is defined as the forced egress of stem cells from the bone marrow to the peripheral blood (PB) using chemokine receptor agonists, is an emerging concept for enhancing tissue regeneration. However, the effect of stem cell mobilization by a single injection of the C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 on intramembranous bone regeneration is unclear. We therefore asked: Does AMD3100 mobilize adult stem cells in C57BL/6 mice? Are stem cells mobilized to the PB after marrow ablation? And does AMD3100 enhance bone regeneration? Female C57BL/6 mice underwent femoral marrow ablation surgery alone (n = 25), systemic injection of AMD3100 alone (n = 15), or surgery plus AMD3100 (n = 57). We used colony-forming unit assays, flow cytometry, and micro-CT to investigate mobilization of mesenchymal stem cells, endothelial progenitor cells, and hematopoietic stem cells to the PB and bone regeneration. AMD3100 induced mobilization of stem cells to the PB, resulting in a 40-fold increase in mesenchymal stem cells. The marrow ablation injury mobilized all three cell types to the PB over time. Administration of AMD3100 led to a 60% increase in bone regeneration at Day 21. A single injection of a CXCR4 antagonist lead to stem cell mobilization and enhanced bone volume in the mouse marrow ablation model of intramembranous bone regeneration.

  17. Increased EZH2 and decreased osteoblastogenesis during local irradiation-induced bone loss in rats

    PubMed Central

    Guo, Changjun; Li, Changwei; Yang, Kai; Kang, Hui; Xu, Xiaoya; Xu, Xiangyang; Deng, Lianfu

    2016-01-01

    Radiation therapy is commonly used to treat cancer patients but exhibits adverse effects, including insufficiency fractures and bone loss. Epigenetic regulation plays an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, we reported local bone changes after single-dose exposure to 137CS irradiation in rats. Femur bone mineral density (BMD) and trabecular bone volume in the tibia were significantly decreased at 12 weeks after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also significantly reduced at 12 weeks after irradiation exposure. ALP-positive OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by 50.8% at 12 weeks after exposure. In contrast to the decreased expression of Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks after single-dose 137CS irradiation in BMSCs. Together, our results demonstrated that single-dose 137CS irradiation induces BMD loss and the deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2 expression increased and osteoblastogenesis decreased after irradiation. The underlying mechanisms warrant further investigation. PMID:27499068

  18. Sirt1 is involved in decreased bone formation in aged apolipoprotein E-deficient mice

    PubMed Central

    Hong, Wei; Xu, Xiao-ya; Qiu, Zhao-hui; Gao, Jian-jun; Wei, Zhan-ying; Zhen, Li; Zhang, Xiao-li; Ye, Zhi-bing

    2015-01-01

    Aim: Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE−/− mice. In this study we investigated the bone phenotype and metabolism in aged apoE−/− mice. Methods: Femurs and tibias were collected from 18- and 72-week-old apoE−/− mice and their age-matched wild-type (WT) littermates, and examined using micro-CT and histological analysis. Serum levels of total cholesterol, oxidized low-density lipoprotein (ox-LDL) and bone turnover markers were measured. Cultured bone mesenchymal stem cells (BMSCs) from tibias and femurs of 18-week-old apoE−/− mice were used in experiments in vitro. The expression levels of Sirt1 and Runx2 in bone tissue and BMSCs were measured using RT-PCR and Western blot analysis. Results: Compared with age-matched WT littermates, young apoE−/− mice exhibited high bone mass with increased bone formation, accompanied by higher serum levels of bone turnover markers OCN and TRAP5b, and higher expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. In contrast, aged apoE−/− mice showed reduced bone formation and lower bone mass relative to age-matched WT mice, accompanied by lower serum OCN levels, and markedly reduced expression levels of Sirt1, Runx2, ALP and OCN in bone tissue. After BMSCs were exposed to ox-LDL (20 μg/mL), the expression of Sirt1 and Runx2 proteins was significantly increased at 12 h, and then decreased at 72 h. Treatment with the Sirt1 inhibitor EX527 (10 μmol/L) suppressed the expression of Runx2, ALP and OCN in BMSCs. Conclusion: In contrast to young apoE−/− mice, aged apoE−/− mice showe lower bone mass than age-matched WT mice. Long-lasting exposure to ox-LDL decreases the expression of Sirt1 and Runx2 in BMSCs, which may explain the decreased bone formation in aged apoE−/− mice. PMID:26592520

  19. [Frequency and some risk factors of decreased bone mineralization in a group of university students].

    PubMed

    Trafalska, Elzbieta; Grzybowski, Andrzej; Błaszczyk, Agnjeszka; Chlebna-Sokół, Danuta

    2003-01-01

    The aim of the study was to evaluate the frequency of occurrence of decreased bone mineralization in the group of university students and qualification of dependence between this abnormality and dietary factors and nutritional status. 110 subjects (63 females and 47 males) aged 21-26 years from Medical University of Lodz participated in this study. All persons were recognized as healthy, without any disturbances in skeletal and muscle systems reported in anamnesis. Bone mineralization was evaluated by ultrasound examination of the calcaneal bone with Achilles Solo plus apparatus. Speed of Sound (SOS), Broadband Ultrasound Attenuation (BUA) and Stiffness index were analysed. 24-hour recall of dietary intake was collected and the analysis was performed using FOOD 3.1 nutritional programme. Anthropometrical measurements were estimated (weight, height, Body Mass Index) and the body composition was analysed (percent of body fat [BF%], fat mass [FM], fat-free mass [FFM]) using near-infrared spectrophotometry with FUTREX 5000 A/ZL. The decreased bone mineralization was observed in 12.6% of women and in 10.6% of men. The mean values of parameters of ultrasound examination were statistically lower in the group with decreased bone mineralization; in women lower than in men. 27.7% males and 6.4% females had grade 1 overweight, 2.1% men and 17.4% women--grade 1 thinness. Diets of persons' with reduced ultrasound parameters had lower content of calcium, phosphorus, magnesium, potassium, vitamin D and C, simultaneously having higher content of protein and sodium. Students with decreased bone mineralization had higher BMI, higher BF% and lower FFM. Persons with decreased bone mineralization had a diet with an unbalanced intake of nutrients influencing the process of shaping the peak bone mass and an incorrect nutritional status.

  20. Decreased Bone Formation and Osteopenia in Lamin A/C-Deficient Mice

    PubMed Central

    Vidal, Christopher; McCorquodale, Thomas; Herrmann, Markus; Fatkin, Diane; Duque, Gustavo

    2011-01-01

    Age-related bone loss is associated with changes in bone cellularity with characteristically low levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although recent in vitro evidence has suggested a new role for proteins of the nuclear envelope in osteoblastogenesis, the role of these proteins in bone cells differentiation and bone metabolism in vivo remains unknown. In this study, we used the lamin A/C null (Lmna−/−) mice to identify the role of lamin A/C in bone turnover and bone structure in vivo. At three weeks of age, histological and micro computed tomography measurements of femurs in Lmna−/− mice revealed a significant decrease in bone mass and microarchitecture in Lmna−/− mice as compared with their wild type littermates. Furthermore, quantification of cell numbers after normalization with bone surface revealed a significant reduction in osteoblast and osteocyte numbers in Lmna−/− mice compared with their WT littermates. In addition, Lmna−/− mice have significantly lower osteoclast number, which show aberrant changes in their shape and size. Finally, mechanistic analysis demonstrated that absence of lamin A/C is associated with increase expression of MAN-1 a protein of the nuclear envelope closely regulated by lamin A/C, which also colocalizes with Runx2 thus affecting its capacity as osteogenic transcription factor. In summary, these data clearly indicate that the presence of lamin A/C is necessary for normal bone turnover in vivo and that absence of lamin A/C induces low bone turnover osteopenia resembling the cellular changes of age-related bone loss. PMID:21547077

  1. Histone Deacetylase 3 Depletion in Osteo/Chondroprogenitor Cells Decreases Bone Density and Increases Marrow Fat

    PubMed Central

    Casper, Michelle E.; McGee-Lawrence, Meghan E.; Stensgard, Bridget A.; Li, Xiaodong; Secreto, Frank J.; Knutson, Sarah K.; Hiebert, Scott W.; Westendorf, Jennifer J.

    2010-01-01

    Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health. PMID:20628553

  2. Minodronic acid (ONO-5920/YM529) prevents decrease in bone mineral density and bone strength, and improves bone microarchitecture in ovariectomized cynomolgus monkeys.

    PubMed

    Mori, Hiroshi; Tanaka, Makoto; Kayasuga, Ryoji; Masuda, Taisei; Ochi, Yasuo; Yamada, Hiroyuki; Kishikawa, Katsuya; Ito, Masako; Nakamura, Toshitaka

    2008-11-01

    This study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX) cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years, were ovariectomized or sham-operated. Minodronic acid was administered orally once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17 months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose-dependently inhibited OVX-induced increase in bone turnover markers and decrease in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented these changes. At 17 months after surgery, minodronic acid also suppressed bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS, and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests, ultimate load on lumbar vertebral bodies and femoral neck of the OVX-control animals were significantly reduced compared to the sham animals. Minodronic acid prevented these reductions in bone strength at 0.15 mg/kg. There was significant correlation between BMD and bone strength, suggesting that the increase in bone strength was associated with the increase in BMD produced by minodronic acid. In micro-CT analysis of the lumbar vertebral bodies, minodronic acid improved trabecular architecture, converting rod structures into plate structures, and preventing the increase in trabecular disconnectivity at 0.15 mg/kg. In conclusion, similar to patients with postmenopausal osteoporosis, reduction in bone strength of lumbar vertebral bodies and femoral neck was clearly demonstrated in OVX

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

    PubMed

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

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

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

    PubMed Central

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

    2008-01-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis. PMID:18037367

  5. Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength.

    PubMed

    Ammann, Patrick; Brennan, Tara C; Mekraldi, Samia; Aubert, Michel L; Rizzoli, René

    2010-06-01

    Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

    PubMed

    Wang, Chun-Hua; Chou, Pai-Chien; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Ho, Shu-Chuan; Lin, Horng-Chyuan; Huang, Chien-Da; Chung, Fu-Tsai; Chung, Kian Fan; Kuo, Han-Pin

    2014-08-30

    Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019).

  7. Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study

    PubMed Central

    2014-01-01

    Background Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. Methods To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. Results Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. Conclusions A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019) PMID:25175787

  8. Fractures in geriatric mice show decreased callus expansion and bone volume.

    PubMed

    Lopas, Luke A; Belkin, Nicole S; Mutyaba, Patricia L; Gray, Chancellor F; Hankenson, Kurt D; Ahn, Jaimo

    2014-11-01

    Poor fracture healing in geriatric populations is a significant source of morbidity, mortality, and cost to individuals and society; however, a fundamental biologic understanding of age-dependent healing remains elusive. The development of an aged-based fracture model system would allow for a mechanistic understanding that could guide future biologic treatments. Using a small animal model of long-bone fracture healing based on chronologic age, we asked how aging affected (1) the amount, density, and proportion of bone formed during healing; (2) the amount of cartilage produced and the progression to bone during healing; (3) the callus structure and timing of the fracture healing; and (4) the behavior of progenitor cells relative to the observed deficiencies of geriatric fracture healing. Transverse, traumatic tibial diaphyseal fractures were created in 5-month-old (n=104; young adult) and 25-month-old (n=107; which we defined as geriatric, and are approximately equivalent to 70-85 year-old humans) C57BL/6 mice. Fracture calluses were harvested at seven times from 0 to 40 days postfracture for micro-CT analysis (total volume, bone volume, bone volume fraction, connectivity density, structure model index, trabecular number, trabecular thickness, trabecular spacing, total mineral content, bone mineral content, tissue mineral density, bone mineral density, degree of anisotropy, and polar moment of inertia), histomorphometry (total callus area, cartilage area, percent of cartilage, hypertrophic cartilage area, percent of hypertrophic cartilage area, bone and osteoid area, percent of bone and osteoid area), and gene expression quantification (fold change). The geriatric mice produced a less robust healing response characterized by a pronounced decrease in callus amount (mean total volume at 20 days postfracture, 30.08±11.53 mm3 versus 43.19±18.39 mm3; p=0.009), density (mean bone mineral density at 20 days postfracture, 171.14±64.20 mg hydroxyapatite [HA]/cm3 versus

  9. Imbalance between bone formation and resorption in hematopoietic stem/progenitor cells mobilization.

    PubMed

    Li, S-D; Zhai, Q-L; Qiu, L-G

    2011-12-01

    Mobilization is now used worldwide to collect large numbers of hematopoietic stem and progenitor cells (HSPCs) for transplantation. It is the result of a process impelling stem cell detachment from their niche, meanwhile gaining cellular features required for proliferation and migration. Mobilization remarkably affects the endosteal stem cell niche, which must be adjusted to support retention and quiescence versus mobilization and proliferation. The endosteal bone-lining cells, osteoblasts and osteoclasts, not only maintain bone balance but also participate in HSPC mobilization. The aim of this paper was to review recent advances in our understanding of HSPC mobilization and how these advances are being translated into the clinic for more efficacious mobilizing agents. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Fixed and mobile-bearing total ankle prostheses: Effect on tibial bone strain.

    PubMed

    Terrier, Alexandre; Fernandes, Caroline Sieger; Guillemin, Maïka; Crevoisier, Xavier

    2017-10-01

    Total ankle replacement is associated to a high revision rate. To improve implant survival, the potential advantage of prostheses with fixed bearing compared to mobile bearing is unclear. The objective of this study was to test the hypothesis that fixed and mobile bearing prostheses are associated with different biomechanical quantities typically associated to implant failure. With a validated finite element model, we compared three cases: a prosthesis with a fixed bearing, a prosthesis with a mobile bearing in a centered position, and a prosthesis with mobile bearing in an eccentric position. Both prostheses were obtained from the same manufacturer. They were tested on seven tibias with maximum axial compression force during walking. We tested the hypothesis that there was a difference of bone strain, bone-implant interfacial stress, and bone support between the three cases. We also evaluated, for the three cases, the correlations between bone support, bone strain and bone-implant interfacial stress. There were no statistically significant differences between the three cases. Overall, bone support was mainly trabecular, and less effective in the posterior side. Bone strain and bone-implant interfacial stress were strongly correlated to bone support. Even if slight differences are observed between fixed and mobile bearing, it is not enough to put forward the superiority of one of these implants regarding their reaction to axial compression. When associated to the published clinical results, our study provides no argument to warn surgeons against the use of two-components fixed bearing implants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. N-acetylcysteine supplementation decreases osteoclast differentiation and increases bone mass in mice fed a high-fat diet

    USDA-ARS?s Scientific Manuscript database

    Studies have demonstrated that obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. This study investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters glutathione statu...

  12. High intake of milk, but not meat, decreases bone turnover in prepubertal boys after 7 days.

    PubMed

    Budek, A Z; Hoppe, C; Michaelsen, K F; Mølgaard, C

    2007-08-01

    To compare the short-term effect of a high milk and a high meat intake, identical in protein amount, on bone turnover during prepuberty. A University department. From 28, randomly recruited, 8-year-old boys, first 14 were assigned to the milk group and next 14 to the meat group. In each group, 12 boys finished the dietary intervention. Milk (1.5 l/day) and meat (250 g/d), both containing approximately 53 g of protein, were given together with the habitual diet for 7 days. At baseline and day-7, serum osteocalcin (s-OC), bone-specific alkaline phosphatase (s-BAP) and C-terminal telopeptides of type I collagen (s-CTX) were measured (immunoassay) and dietary intake was estimated (a 3-day weighted food record). Baseline s-OC, s-BAP and s-CTX were not significantly different between the groups. After 7 days, the average protein intake increased in both groups by 47.5 g; the milk group had higher (P<0.0001) calcium intake; s-OC and s-CTX decreased (P< or =0.04) in the milk group (-30.9%; -18.7%, respectively) compared with the meat group (+6.4%; -1.0%, respectively) and s-BAP decreased (P=0.06) both in the milk (-3.9%) and the meat group (-7.5%). At the equal protein intake, milk, but not meat, decreased bone turnover in prepubertal boys after 7 days. This effect was probably due to some milk-derived compounds, rather than to the total protein intake. Future studies should elucidate the mechanism(s) of milk-related decline of bone turnover and its relevance for peak bone mass during growth. University PhD scholarships.

  13. Risedronate decreases bone resorption and improves low back pain in postmenopausal osteoporosis patients without vertebral fractures.

    PubMed

    Ohtori, Seiji; Akazawa, Tsutomu; Murata, Yasuaki; Kinoshita, Tomoaki; Yamashita, Masaomi; Nakagawa, Koichi; Inoue, Gen; Nakamura, Junichi; Orita, Sumihisa; Ochiai, Nobuyasu; Kishida, Shunji; Takaso, Masashi; Eguchi, Yawara; Yamauchi, Kazuyo; Suzuki, Munetaka; Aoki, Yasuchika; Takahashi, Kazuhisa

    2010-02-01

    Elderly postmenopausal women who have osteoporosis sometimes experience low back pain, however, the relationship between low back pain and osteoporosis in the absence of vertebral fractures remains unclear. We examined the relationship between bone mineral density (BMD), bone resorption and low back pain in elderly female patients who did not have osteoporotic vertebral fractures. The average BMD was 0.675 g/cm(2) when assessed by dual-energy X-ray absorptiometry (DEXA). Patients were excluded from the study if they had vertebral fractures revealed by radiography, CT scans or MRI. Bisphosphonate (risedronate) was administered for 4 months. The visual analogue scale (VAS) pain score, Roland Morris Disability Questionnaire (RDQ), Short Form-36 (SF-36) questionnaire, BMD and N-terminal telopeptide of type I collagen (NTx; a marker for bone resorption) were examined before and after treatment. DEXA did not increase significantly, but serum and urinary NTx were decreased (-51.4% and -62.0%, respectively) after 4 months of risedronate treatment (p<0.01). The assessment was repeated using the VAS score, RDQ and SF-36, which revealed an improvement after risedronate treatment (p<0.01). A decrease in serum and urinary NTx was associated with improvement of low back pain, suggesting that despite the absence of vertebral fractures, bone resorption due to osteoporosis may cause low back pain. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. Diabetes impairs mobilization of mouse bone marrow-derived Lin(-)/VEGF-R2(+) progenitor cells.

    PubMed

    Barthelmes, D; Irhimeh, M R; Gillies, M C; Karimipour, M; Zhou, M; Zhu, L; Shen, W Y

    2013-10-01

    Endothelial progenitor cells circulating in the peripheral blood (PB) contribute to vascular repair. This study aimed to evaluate the potential of a 'cocktail' consisting of erythropoietin, granulocyte colony-stimulating factor and tetrahydrobiopterin to mobilize hematopoietic lineage negative/vascular endothelial growth factor receptor 2 positive (Lin(-)/VEGF-R2(+)) cells from the bone marrow (BM) to PB in non-diabetic and diabetic mice. Diabetes was induced in mice by intraperitoneal injection of streptozotocin. Diabetic mice were studied after 16weeks of hyperglycemia. Half the mice in each group (non-diabetic and diabetic) received daily intraperitoneal injections of the cocktail for 6 consecutive days while the other half received vehicle buffer. Mobilization of Lin(-)/VEGF-R2(+) cells, which were expanded in MCP301 medium, was evaluated after isolating them from BM and PB and their phenotypic and morphological properties were studied. We found that 16weeks of diabetes affected neither the total number of BM mononucleated cells nor the number of Lin(-)/VEGF-R2(+) cells in BM compared with non-diabetic controls. In non-diabetic mice, cocktail treatment resulted in a significant decrease in BM Lin(-)/VEGF-R2(+) cells, paralleled by a significant increase of these cells in PB. Such changes in the number of Lin(-)/VEGF-R2(+) cells in BM and PB after the cocktail treatment were less marked in diabetic mice. In vitro studies of BM Lin(-)/VEGF-R2(+) cells from diabetic and non-diabetic mice did not reveal any differences in either phenotypes or colony forming potential. These findings indicate that diabetes impairs the mobilization of Lin(-)/VEGF-R2(+) cells from BM to PB. Impaired mobilization of BM Lin(-)/VEGF-R2(+) cells soon after the onset of diabetes may contribute to complications such as diabetic retinopathy.

  15. Decreased Salinity and Actinide Mobility: Colloid-Facilitated Transport or pH Change?

    PubMed

    Haliena, Brian; Zheng, Hangping; Melson, Nathan; Kaplan, Daniel I; Barnett, Mark O

    2016-01-19

    Colloids have been implicated in influencing the transport of actinides and other adsorbed contaminants in the subsurface, significantly increasing their mobility. Such colloid-facilitated transport can be induced by changes in groundwater chemistry that occur, for example, when high ionic strength contaminant plumes are displaced by infiltrating rainwater. We studied the transport and mobility of Th(IV), as an analogue for Pu(IV) and other tetravalent actinides [An(IV)], in saturated columns packed with a natural heterogeneous subsurface sandy sediment. As expected, decreases in ionic strength both promoted the mobilization of natural colloids and enhanced the transport of previously adsorbed Th(IV). However, colloid-facilitated transport played only a minor role in enhancing the transport of Th(IV). Instead, the enhanced transport of Th(IV) was primarily due to the pH-dependent desorption of Th(IV) caused by the change in ionic strength. In contrast, the adsorption of Th(IV) had a marked impact on the surface charge of the sandy sediment, significantly affecting the mobility of the colloids. In the absence of Th(IV), changes in ionic strength were ineffective at releasing colloids while in the presence of Th(IV), decreases in ionic strength liberated significant concentrations of colloids. Therefore, under the conditions of our experiments which mimicked acidic, high ionic strength groundwater contaminant plumes, Th(IV) had a much greater effect on colloid transport than colloids had on Th(IV) transport.

  16. Potential Association of Posttraumatic Stress Disorder and Decreased Bone Mineral Density in Repatriated Prisoners of War

    DTIC Science & Technology

    2011-03-01

    the US. All rights reserved. MILITARY MEDICINE, 176, 3:270, 2011 270 MILITARY MEDICINE, Vol. 176, March 2011 INTRODUCTION Osteoporosis is defi ned...and susceptibility to fracture. 1 Male osteoporosis is a less well- recognized and studied condition compared to osteoporosis in women. It is known...that approximately 1–2 million men in the United States have osteoporosis and another 8–13 million have osteopenia or decreased bone mass. 2 One-third

  17. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    PubMed

    Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

    2013-01-01

    Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  18. Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

    PubMed Central

    Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

    2013-01-01

    Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

  19. Identifying decreased diaphragmatic mobility and diaphragm thickening in interstitial lung disease: the utility of ultrasound imaging

    PubMed Central

    Santana, Pauliane Vieira; Prina, Elena; Albuquerque, André Luis Pereira; Carvalho, Carlos Roberto Ribeiro; Caruso, Pedro

    2016-01-01

    Objective: To investigate the applicability of ultrasound imaging of the diaphragm in interstitial lung disease (ILD). Methods: Using ultrasound, we compared ILD patients and healthy volunteers (controls) in terms of diaphragmatic mobility during quiet and deep breathing; diaphragm thickness at functional residual capacity (FRC) and at total lung capacity (TLC); and the thickening fraction (TF, proportional diaphragm thickening from FRC to TLC). We also evaluated correlations between diaphragmatic dysfunction and lung function variables. Results: Between the ILD patients (n = 40) and the controls (n = 16), mean diaphragmatic mobility was comparable during quiet breathing, although it was significantly lower in the patients during deep breathing (4.5 ± 1.7 cm vs. 7.6 ± 1.4 cm; p < 0.01). The patients showed greater diaphragm thickness at FRC (p = 0.05), although, due to lower diaphragm thickness at TLC, they also showed a lower TF (p < 0.01). The FVC as a percentage of the predicted value (FVC%) correlated with diaphragmatic mobility (r = 0.73; p < 0.01), and an FVC% cut-off value of < 60% presented high sensitivity (92%) and specificity (81%) for indentifying decreased diaphragmatic mobility. Conclusions: Using ultrasound, we were able to show that diaphragmatic mobility and the TF were lower in ILD patients than in healthy controls, despite the greater diaphragm thickness at FRC in the former. Diaphragmatic mobility correlated with ILD functional severity, and an FVC% cut-off value of < 60% was found to be highly accurate for indentifying diaphragmatic dysfunction on ultrasound. PMID:27167428

  20. Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

    NASA Astrophysics Data System (ADS)

    Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

    2015-02-01

    The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

  1. Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice.

    PubMed

    Wakabayashi, Hiroki; Wakisaka, Satoshi; Hiraga, Toru; Hata, Kenji; Nishimura, Riko; Tominaga, Makoto; Yoneda, Toshiyuki

    2017-05-17

    Bone pain is one of the most common and life-limiting complications of cancer metastasis to bone. Although the mechanism of bone pain still remains poorly understood, bone pain is evoked as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by noxious stimuli produced in the microenvironment of bone metastases. We showed that bone is innervated by calcitonin gene-related protein (CGRP)(+) SNs extending from dorsal root ganglia (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia and flinching with increased CGRP(+) SNs in bone and augmented SN excitation in DRG as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons. Immunohistochemical examination of LLC-injected bone revealed that the tumor microenvironment is acidic. Bafilomycin A1, a selective inhibitor of H(+) secretion from vacuolar proton pump, significantly alleviated bone pain, indicating that the acidic microenvironment contributes to bone pain. We then determined whether the transient receptor potential vanilloid 1 (TRPV1), a major acid-sensing nociceptor predominantly expressed on SNs, plays a role in bone pain by intratibially injecting LLC cells in TRPV1-deficient mice. Bone pain and SN excitation in the DRG and spinal dorsal horn were significantly decreased in TRPV1 (-/-) mice compared with wild-type mice. Our results suggest that TRPV1 activation on SNs innervating bone by the acidic cancer microenvironment in bone contributes to SN activation and bone pain. Targeting acid-activated TRPV1 is a potential therapeutic approach to cancer-induced bone pain.

  2. Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds

    PubMed Central

    Zhang, Xianjie; Sarkar, Kakali; Rey, Sergio; Sebastian, Raul; Andrikopoulou, Efstathia; Marti, Guy P.; Fox-Talbot, Karen

    2013-01-01

    Impaired wound healing in the elderly represents a major clinical problem. Delineating the cellular and molecular mechanisms by which aging impairs wound healing may lead to the development of improved treatment strategies for elderly patients with non-healing wounds. Neovascularization is an essential step in wound healing, and bone marrow-derived angiogenic cells (BMDACs) play an important role in vascularization. Using a mouse full-thickness burn wound model, we demonstrate that perfusion and vascularization of burn wounds were impaired by aging and were associated with dramatically reduced mobilization of BMDACs bearing the cell surface molecules CXCR4 and Sca1. Expression of stromal-derived factor 1 (SDF-1), the cytokine ligand for CXCR4, was significantly decreased in peripheral blood and burn wounds of old mice. Expression of hypoxia-inducible factor (HIF)-1α was detected in burn wounds from young (2-month-old), but not old (2-year-old), mice. When BMDACs from young donor mice were injected intravenously, homing to burn wound tissue was impaired in old recipient mice, whereas the age of the BMDAC donor mice had no effect on homing. Our results indicate that aging impairs burn wound vascularization by impairing the mobilization of BMDACs and their homing to burn wound tissue as a result of impaired HIF-1 induction and SDF-1 signaling. PMID:21499736

  3. Low Dose Aspirin Therapy Decreases Blood Glucose Levels but Does not Prevent Type I Diabetes-induced Bone Loss

    PubMed Central

    Coe, Lindsay M.; Denison, Jeffery D.; McCabe, Laura R.

    2011-01-01

    Backgroud: Diabetes is strongly associated with increased fracture risk. During T1-diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including TNFα) are increased. At the same time, levels of osteoblast markers are rapidly decreased and stay decreased 40 days later at which point bone loss is clearly evident. Inflammation is known to suppress bone formation and induce bone loss. Previous co-culture studies indicate that diabetic bone is inflamed and diabetic bone marrow is capable of enhancing osteoblast death in vitro. Here we investigate a commonly used non-steroidal anti-inflammatory drug, aspirin, to prevent T1-diabetic bone loss in vivo. Methods: We induced diabetes in 16-week-old male C57BL/6 mice and administered aspirin in the drinking water. Results: Our results demonstrate that aspirin therapy reduced diabetic mouse non-fasting blood glucose levels to less than 400 mg/dl, but did not prevent trabecular and cortical bone loss. In control mice, aspirin treatment increased bone formation markers but did not affect markers of bone resorption or bone density/volume. In diabetic mice, bone formation markers and bone density/volume are decreased and unaltered by aspirin treatment. Bone resorption markers, however, are increased and 2-way ANOVA analysis demonstrates an interaction between aspirin treatment and diabetes (p<0.007). Aspirin treatment did not prevent the previously reported diabetes-induced marrow adiposity. Conclusion: Taken together, our results suggest that low dose aspirin therapy does not negatively impact bone density in control and diabetic mice, but could potentially increase bone resorption in T1-diabetic mice. PMID:22178944

  4. Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow

    PubMed Central

    Kwak, Hyeongil; Salvucci, Ombretta; Weigert, Roberto; Martinez-Torrecuadrada, Jorge L.; Henkemeyer, Mark; Poulos, Michael G.; Butler, Jason M.

    2016-01-01

    Hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow. Stress signals from cancer and other conditions promote HSPC mobilization into circulation and subsequent homing to tissue microenvironments. HSPC infiltration into tissue microenvironments can influence disease progression; notably, in cancer, HSPCs encourage tumor growth. Here we have uncovered a mutually exclusive distribution of EPHB4 receptors in bone marrow sinusoids and ephrin B2 ligands in hematopoietic cells. We determined that signaling interactions between EPHB4 and ephrin B2 control HSPC mobilization from the bone marrow. In mice, blockade of the EPHB4/ephrin B2 signaling pathway reduced mobilization of HSPCs and other myeloid cells to the circulation. EPHB4/ephrin B2 blockade also reduced HSPC infiltration into tumors as well as tumor progression in murine models of melanoma and mammary cancer. These results identify EPHB4/ephrin B2 signaling as critical to HSPC mobilization from bone marrow and provide a potential strategy for reducing cancer progression by targeting the bone marrow. PMID:27820703

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

    PubMed

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

    2012-07-01

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

  6. Bone mineral density is decreased in fibromyalgia syndrome: a systematic review and meta-analysis.

    PubMed

    Upala, Sikarin; Yong, Wai Chung; Sanguankeo, Anawin

    2017-04-01

    Previous studies have shown that fibromyalgia syndrome (FMS) is associated with low level of physical activity and exercise, which may lead to an increased risk of osteoporosis. However, studies of bone mineral density (BMD) in fibromyalgia have shown conflicting results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between FMS and BMD. A comprehensive search of the databases MEDLINE and EMBASE was performed from inception through May 2016. The inclusion criterion was the observational studies' assessment of the association between fibromyalgia and bone mineral density in adult subjects. Fibromyalgia was diagnosed in accordance with the American College of Rheumatology criteria for the diagnosis of fibromyalgia syndrome. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Pooled mean difference (MD) of BMD at each site and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The between-study heterogeneity of effect size was quantified using the Q statistic and I (2). Data were extracted from four observational studies involving 680 subjects. At lumbar spine (L2-L4), BMD is significantly decreased in patients with FMS compared with controls with pooled MD of -0.02 (95% CI -0.03 to -0.01, P value = 0.003, I (2) = 0%) (Fig. 1). At femoral neck, BMD is not significantly decreased in patients with FMS compared with controls with pooled MD of 0.01 (95% CI -0.02 to 0.01, P value = 0.23, I (2) = 0%) (Fig. 2). In this meta-analysis, we observe that BMD at lumbar spine is decreased in FMS compared with normal individuals. Patients with FMS should be assessed for risk of osteoporosis. Fig. 1 Forest plot of bone mineral density at the lumbar spine, for patients with and without fibromyalgia syndrome. CI-confidence interval Fig. 2 Forest plot of bone mineral density at the femoral neck, for patients with and without

  7. The brain-bone-blood triad: traffic lights for stem-cell homing and mobilization.

    PubMed

    Lapidot, Tsvee; Kollet, Orit

    2010-01-01

    Navigation of transplanted stem cells to their target organs is essential for clinical bone marrow reconstitution. Recent studies have established that hematopoietic stem cells (HSCs) dynamically change their features and location, shifting from quiescent and stationary cells anchored in the bone marrow to cycling and motile cells entering the circulation. These changes are driven by stress signals. Bidirectional migrations to and from the bone marrow are active processes that form the basis for HSC transplantation protocols. However, how and why HSCs enter and exit the bone marrow as part of host defense and repair is not fully understood. The development of functional, preclinical, immune-deficient NOD/SCID (non-obese diabetic-severe combined immunodeficiency) mice transplantation models has enabled the characterization of normal and leukemic human HSCs and investigation of their biology. Intensive research has revealed multiple tasks for the chemokine SDF-1 (stromal cell-derived factor-1, also known as CXCL12) in HSC interactions with the microenvironment, as well as the existence of overlapping mechanisms controlling stress-induced mobilization and enhanced HSC homing, sequential events of major physiological relevance. These processes entail dynamically interacting, multi-system aspects that link the bone marrow vasculature and stromal cells with the nervous and immune systems. Neural cues act as an external pacemaker to synchronize HSC migration and development to balance bone remodeling via circadian rhythms in order to address blood and immune cell production for the physiological needs of the body. Stress situations and clinical HSC mobilization accelerate leukocyte proliferation and bone turnover. This review presents the concept that HSC regulation by the brain-bone-blood triad via stress signals controls the bone marrow reservoir of immature and maturing leukocytes.

  8. Decreased bone mineral density and fractures in low-income Korean women.

    PubMed

    Yang, Kyunghee; McElmurry, Beverly J; Park, Chang G

    2006-03-01

    Low-income Korean community women were assessed for factors relating to decreased bone mineral density (BMD) and fractures in order to determine appropriate health promotion programs. Factors associated with decreased BMD were menopause (OR=3.30, p<0.01), menarchal age (OR=2.01, p<0.05), thyroxin (T(4); OR=11.32, p<0.05), age (OR=2.19, p<0.1), marital status (OR=0.56, p<.01), oral contraceptive use (OR=2.18, p<.01), and tubal ligation (OR=3.30, p<0.1). The risk factors for fractures were earlier menarchal age (OR=13.15, p<0.05), urban residency (OR=0.75, p<0.05), and T(4) abnormality (OR=64.29, p<0.1). The beneficial factor for decreased incidence of fractures was physical activity (OR=40.94, p<0.05). The strategy recommended for fracture risk reduction programs is focused on the prevention of both decreased BMD and fractures. Continuous physical activity should be encouraged as well as reduction of risk factors including associated risk behaviors.

  9. Rethinking critical care: decreasing sedation, increasing delirium monitoring, and increasing patient mobility.

    PubMed

    Bassett, Rick; Adams, Kelly McCutcheon; Danesh, Valerie; Groat, Patricia M; Haugen, Angie; Kiewel, Angi; Small, Cora; Van-Leuven, Mark; Venus, Sam; Ely, E Wesley

    2015-02-01

    Sedation management, delirium monitoring, and mobility programs have been addressed in evidence-based critical care guidelines and care bundles, yet implementation in the ICU remains variable. As critically ill patients occupy higher percentages of hospital beds in the United States and beyond, it is increasingly important to determine mechanisms to deliver better care. The Institute for Healthcare Improvement's Rethinking Critical Care (IHI-RCC) program was established to reduce harm of critically ill patients by decreasing sedation, increasing monitoring and management of delirium, and increasing patient mobility. Case studies of a convenience sample of five participating hospitals/health systems chosen in advance of the determination of their clinical outcomes are presented in terms of how they got started and process improvements in sedation management, delirium management, and mobility. The IHI-RCC program involved one live case study and five iterations of an in-person seminar in a 33-month period (March 2011-November 2013) that emphasized interdisciplinary teamwork and culture change. Qualitative descriptions of the changes tested at each of the five case study sites demonstrate improvements in teamwork, processes, and reliability of daily work. Improvement in ICU length of stay and length of stay on the ventilator between the pre- and postimplementation periods varied from slight to substantial. Changing critical care practices requires an interdisciplinary approach addressing cultural, psychological, and practical issues. The key lessons of the IHI-RCC program are as follows: the importance of testing changes on a small scale, feeding back data regularly and providing sufficient education, and building will through seeing the work in action.

  10. Relative bone mass decreased in mice fed high dietary fat despite an increase in body mass and bone formation markers

    USDA-ARS?s Scientific Manuscript database

    Osteoporosis and obesity are interrelated health disorders. Osteoblasts and adipocytes are derived from common mesenchymal stem cells and age-related osteoporosis is associated with increased bone marrow adipogenesis. To determine whether bone mass and osteoblast number and activity are affected by ...

  11. Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1

    PubMed Central

    Arimilli, Subhashini; Sharma, Sharad K.; Yammani, Rama; Reid, Sean D.; Parks, Griffith D.; Alexander-Miller, Martha A.

    2010-01-01

    CD8+ T cells play a critical role in the clearance of respiratory pathogens. Thus, it is surprising that functional inactivation of lung effectors has been observed in many models of viral infection. Currently, the molecular defect responsible for the shut-off of function in these cells is unknown. In the present study, we addressed this question using a model of respiratory infection with the paramyxovirus SV5. Nonfunctional cells were found to exhibit decreases in SOCE, resulting in reduced NFAT1 activation. Notably, function could be restored by the provision of increased levels of extracellular calcium. The reduced ability to mobilize calcium was associated with reduced expression of ORAI1, the CRAC channel subunit. These findings reveal a previously unknown mechanism for the negative regulation of function in effector T cells. PMID:20103768

  12. Decreased bone mineral density is associated with coronary atherosclerosis in healthy postmenopausal women

    PubMed Central

    Seo, Seok Kyo; Yun, Bo Hyon; Noe, Eun Bee; Suh, Jong Wook; Choi, Young Sik

    2015-01-01

    Objective This study aimed to assess the association between bone mineral density (BMD) and coronary atherosclerosis in healthy postmenopausal women. Methods We performed a retrospective review of 252 postmenopausal women who had visited a health promotion center for a routine checkup. BMD of the lumbar spine (L1-L4) and femoral neck was evaluated using dual-energy X-ray absorptiometry, and coronary atherosclerosis was assessed using 64-row multidetector computed tomography. Participants were divided into normal BMD and osteopenia-osteoporosis groups, according to the T-scores of their lumbar spine or femoral neck. Results Participants with osteopenia-osteoporosis had a significantly higher proportion of coronary atherosclerosis than did those with normal BMD at the lumbar spine (P=0.003) and femoral neck (P=0.004). Osteopenia-osteoporosis at the lumbar spine (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.12 to 7.27) or femoral neck (OR, 3.35; 95% CI, 1.07 to 10.57) was associated with coronary atherosclerosis, after controlling for age and cardiovascular risk factors. Conclusion Decreased BMD is associated with coronary atherosclerosis in healthy postmenopausal women, independent of age and cardiovascular risk factors. Postmenopausal women with decreased BMD may have a higher risk of developing coronary atherosclerosis. PMID:25798428

  13. Rethinking Critical Care: Decreasing Sedation, Increasing Delirium Monitoring, and Increasing Patient Mobility

    PubMed Central

    Bassett, Rick; Adams, Kelly McCutcheon; Danesh, Valerie; Groat, Patricia M.; Haugen, Angie; Kiewel, Angi; Small, Cora; Van-Leuven, Mark; Venus, Sam; Ely, E. Wesley

    2016-01-01

    Background/Methods Sedation management, delirium monitoring, and mobility programs are key features of recent evidence-based critical care guidelines and care bundles, yet implementation in the intensive care unit (ICU) remains highly variable. The Institute for Healthcare Improvement’s Rethinking Critical Care (IHI-RCC) program was established to reduce harm of critically ill patients by decreasing sedation, increasing monitoring and management of delirium, and increasing patient mobility. It involved one live case study and five iterations of an in-person seminar over 33 months (March 2011 to November 2013) that emphasized interdisciplinary teamwork and culture change. IHI-RCC has involved over 650 participants from 215 organizations. This report describes a convenience sample of five participating organizations chosen in advance of knowing their clinical outcomes. Results Qualitative descriptions of the changes tested at each of the five case study sites are provided, demonstrating the necessary teamwork, improved processes, and increased reliability of daily work. These sites all worked to implement the Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU) within the context of a bundled interventional care plan; they then tracked length of stay in the ICU and duration of mechanical ventilation, which are reported. Discussion Changing critical care practices requires an interdisciplinary approach addressing cultural, psychological, and practical issues. The IHI-RCC program is based on testing changes on a small scale, building highly effective interdisciplinary rounds, frequent data feedback to the frontline, and use of in-person demonstrations. Key lessons are emerging about effectively caring for critically ill patients in light of data about the harm of over-sedation, unrecognized and unaddressed delirium, and immobility. PMID:25976892

  14. Impaired Mobilization of Vascular Reparative Bone Marrow Cells in Streptozotocin-Induced Diabetes but not in Leptin Receptor-Deficient db/db Mice.

    PubMed

    Vasam, Goutham; Joshi, Shrinidh; Jarajapu, Yagna P R

    2016-05-18

    Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-controls were studied. Mobilization induced by G-CSF, AMD3100 or ischemia was evaluated by flow cytometric enumeration of circulating Lin(-)Sca-1(+)cKit(+) (LSK) cells, and by colony forming unit (CFU) assay. The circulating WBCs and LSKs, and CFUs were reduced in both models with a shorter duration (10-12 weeks) of diabetes compared to their respective controls. Longer duration of STZ-diabetes (≥20 weeks) induced impairment of G-CSF- or AMD3100-mobilization (P < 0.01, n = 8). In db/db mice, mobilization by G-CSF or AMD3100 was either increased or unaffected (P < 0.05, n = 6 to 8). Proliferation, migration, and ischemia-induced mobilization, of LSK cells were impaired in both models. Leptin receptor antagonist, PESLAN-1, increased G-CSF- or AMD3100-mobilization of WBCs and LSKs, compared to the untreated. Leptin increased basal WBCs, decreased basal and AMD3100-mobilized LSK cells, and had no effect on G-CSF. These results suggest that mobilopathy is apparent in STZ-diabetes but not in db/db mice. Leptin receptor antagonism would be a promising approach for reversing diabetic bone marrow mobilopathy.

  15. Hematopoietic stem and progenitor cells: their mobilization and homing to bone marrow and peripheral tissue.

    PubMed

    Schulz, Christian; von Andrian, Ulrich H; Massberg, Steffen

    2009-01-01

    Hematopoietic stem and progenitor cells (HSPCs) are a rare population of precursor cells that possess the capacity for self-renewal and multilineage differentiation. In the bone marrow (BM), HSPCs warrant blood cell homeostasis. In addition, they may also replenish tissue-resident myeloid cells and directly participate in innate immune responses once they home to peripheral tissues. In this review, we summarize recent data on the signaling molecules that modulate the mobilization of HSPCs from BM and their migration to peripheral tissues.

  16. SMAD signaling regulates CXCL12 expression in the bone marrow niche, affecting homing and mobilization of hematopoietic progenitors.

    PubMed

    Khurana, Satish; Melacarne, Alessia; Yadak, Rana; Schouteden, Sarah; Notelaers, Tineke; Pistoni, Mariaelena; Maes, Christa; Verfaillie, Catherine M

    2014-11-01

    We recently demonstrated that ex vivo activation of SMAD-independent bone morphogenetic protein 4 (BMP4) signaling in hematopoietic stem/progenitor cells (HSPCs) influences their homing into the bone marrow (BM). Here, we assessed whether alterations in BMP signaling in vivo affects adult hematopoiesis by affecting the BM niche. We demonstrate that systemic inhibition of SMAD-dependent BMP signaling by infusion of the BMP antagonist noggin (NGN) significantly increased CXCL12 levels in BM plasma leading to enhanced homing and engraftment of transplanted HSPCs. Conversely, the infusion of BMP7 but not BMP4, resulted in decreased HSPC homing. Using ST2 cells as an in vitro model of BM niche, we found that incubation with neutralizing anti-BMP4 antibodies, NGN, or dorsomorphin (DM) as well as knockdown of Smad1/5 and Bmp4, all enhanced CXCL12 production. Chromatin immunoprecipitation identified the SMAD-binding element in the CXCL12 promoter to which SMAD4 binds. When deleted, increased CXCL12 promoter activity was observed, and NGN or DM no longer affected Cxcl12 expression. Interestingly, BMP7 infusion resulted in mobilization of only short-term HSCs, likely because BMP7 affected CXCL12 expression only in osteoblasts but not in other niche components. Hence, we describe SMAD-dependent BMP signaling as a novel regulator of CXCL12 production in the BM niche, influencing HSPC homing, engraftment, and mobilization. © 2014 AlphaMed Press.

  17. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    SciTech Connect

    Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

    2010-05-14

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1{beta} was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1{beta} was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1{beta}. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1{beta} expression and thus modulating spinal excitatory synaptic transmission and pain response.

  18. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent.

    PubMed

    Bendall, Linda J; Bradstock, Kenneth F

    2014-08-01

    G-CSF was among the first cytokines to be identified and rapidly transitioned into clinical medicine. Initially used to promote the production of neutrophils in patients with chemotherapy-induced neutropenia it helped to revolutionize the delivery of cancer therapy. Its ability to mobilize hematopoietic stem cells from the bone marrow into the blood was subsequently exploited, changing the face of hematopoietic stem cell transplantation. Today the knowledge gained in unraveling the mechanisms of stem cell mobilization by G-CSF is being explored as a means to increase chemosensitivity in hematological malignancies. This review provides a brief history of G-CSF and then focuses on recent advances in our understanding of G-CSF-induced stem cell mobilization and the potential clinical application of this knowledge in chemo-sensitization. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Development of bone-conduction mobile phones: assessment of hearing mechanisms by measuring psychological characteristics and acoustical properties in the outer ear canal.

    PubMed

    Nakagawa, Seiji; Hotehama, Takuya; Ito, Kazuhito; Inagaki, Tomohiro

    2016-08-01

    We have been developing novel mobile phones using bone conduction, with flat-panel loudspeakers that convey speech sound by vibrating the pinna. In bone conduction via the pinna, i.e., pinna conduction, it is thought that speech sounds are conveyed via both air- and bone-conduction pathways. To obtain useful information for further development of bone-conduction mobile phones, peripheral mechanisms of the pinna conduction need to be clarified. In this study, hearing thresholds, sound field in the outer ear canals, and vibrations of the inner wall of the outer ear canals were measured while normal-hearing participants used pinna-conduction mobile phones. Thresholds decreased linearly as contact pressure increased below 1 kHz, but contact pressure did not affect thresholds above 2 kHz. Additionally, sound fields in the ipsilateral ear canal showed similar results. These results indicate that there is a considerable degree of bone-conduction components from the pinna to the inner ear, which only allow sounds below 1 kHz through. Because similar characteristics were observed in the threshold and the sound field in the outer ear canal, we suggest that osseotympanic emission, sound emission into the ear canal from the inner wall, and air conduction via external auditory foramen are the dominant components of pinna conduction. However, in the vibration measurement, differences between the ipsi- and contra-lateral responses were smaller than the sound field measurement. The smaller inter-lateral differences of the vibration in the outer ear canal suggest the existence of a significant amount of bone-conduction components that directly reach the middle or inner ear. Although the amount of such bone-conduction components does not seem sufficient for pinna.

  20. Stanozolol Decreases Bone Turnover Markers, Increases Mineralization, and Alters Femoral Geometry in Male Rats.

    PubMed

    Nebot, E; Aparicio, V A; Camiletti-Moirón, D; Martinez, R; Erben, R G; Kapravelou, G; Sánchez-González, C; De Teresa, C; Porres, J M; López-Jurado, M; Aranda, P; Pietschmann, P

    2016-06-01

    Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10 mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality.

  1. Obesity induced by high dietary fat leads to increased bone resorption marker, TRAP, and decreased bone mass in mice

    USDA-ARS?s Scientific Manuscript database

    Obesity, which is growing in prevalence, is a risk factor for such chronic health disorders as diabetes and cardiovascular diseases. However, it is thought to be a protective factor for osteoporosis and bone fractures in humans. Accumulating data in humans suggest that fat mass has a negative effect...

  2. Age-related skeletal dynamics and decrease in bone strength in DNA repair deficient male trichothiodystrophy mice.

    PubMed

    Nicolaije, Claudia; Diderich, Karin E M; Botter, S M; Priemel, Matthias; Waarsing, Jan H; Day, Judd S; Brandt, Renata M C; Schilling, Arndt F; Weinans, Harrie; Van der Eerden, Bram C; van der Horst, Gijsbertus T J; Hoeijmakers, Jan H J; van Leeuwen, Johannes P T M

    2012-01-01

    Accumulation of DNA damage caused by oxidative stress is thought to be one of the main contributors of human tissue aging. Trichothiodystrophy (TTD) mice have a mutation in the Ercc2 DNA repair gene, resulting in accumulation of DNA damage and several features of segmental accelerated aging. We used male TTD mice to study the impact of DNA repair on bone metabolism with age. Analysis of bone parameters, measured by micro-computed tomography, displayed an earlier decrease in trabecular and cortical bone as well as a loss of periosteal apposition and a reduction in bone strength in TTD mice with age compared to wild type mice. Ex vivo analysis of bone marrow differentiation potential showed an accelerated reduction in the number of osteogenic and osteoprogenitor cells with unaltered differentiation capacity. Adipocyte differentiation was normal. Early in life, osteoclast number tended to be increased while at 78 weeks it was significantly lower in TTD mice. Our findings reveal the importance of genome stability and proper DNA repair for skeletal homeostasis with age and support the idea that accumulation of damage interferes with normal skeletal maintenance, causing reduction in the number of osteoblast precursors that are required for normal bone remodeling leading to a loss of bone structure and strength.

  3. GDF11 decreases bone mass by stimulating osteoclastogenesis and inhibiting osteoblast differentiation

    PubMed Central

    Liu, Weiqing; Zhou, Liyan; Zhou, Chenchen; Zhang, Shiwen; Jing, Junjun; Xie, Liang; Sun, Ningyuan; Duan, Xiaobo; Jing, Wei; Liang, Xing; Zhao, Hu; Ye, Ling; Chen, Qianming; Yuan, Quan

    2016-01-01

    Osteoporosis is an age-related disease that affects millions of people. Growth differentiation factor 11 (GDF11) is a secreted member of the transforming growth factor beta (TGF-β) superfamily. Deletion of Gdf11 has been shown to result in a skeletal anterior–posterior patterning disorder. Here we show a role for GDF11 in bone remodelling. GDF11 treatment leads to bone loss in both young and aged mice. GDF11 inhibits osteoblast differentiation and also stimulates RANKL-induced osteoclastogenesis through Smad2/3 and c-Fos-dependent induction of Nfatc1. Injection of GDF11 impairs bone regeneration in mice and blocking GDF11 function prevents oestrogen-deficiency-induced bone loss and ameliorates age-related osteoporosis. Our data demonstrate that GDF11 is a previously unrecognized regulator of bone remodelling and suggest that GDF11 is a potential target for treatment of osteoporosis. PMID:27653144

  4. Interaction between bone and muscle in older persons with mobility limitations.

    PubMed

    Ferrucci, L; Baroni, M; Ranchelli, A; Lauretani, F; Maggio, M; Mecocci, P; Ruggiero, C

    2014-01-01

    Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed antisarcopenic interventions in older persons.

  5. Interaction Between Bone and Muscle in Older Persons with Mobility Limitations

    PubMed Central

    Ferrucci, L.; Baroni, M.; Ranchelli, A.; Lauretani, F.; Maggio, M.; Mecocci, P.; Ruggiero, C.

    2015-01-01

    Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed anti-sarcopenic interventions in older persons. PMID:24050165

  6. Decrease of Markers Related to Bone Erosion in Serum of Patients with Musculoskeletal Disorders after Serial Low-Dose Radon Spa Therapy

    PubMed Central

    Cucu, Aljona; Shreder, Kateryna; Kraft, Daniela; Rühle, Paul Friedrich; Klein, Gerhart; Thiel, Gerhard; Frey, Benjamin; Gaipl, Udo S.; Fournier, Claudia

    2017-01-01

    Musculoskeletal disorders (MSDs) are the most frequent cause of disability in Europe. Reduced mobility and quality of life of the patients are often associated with pain due to chronic inflammation. The inflammatory process, accompanied by a destruction of the cartilage and bone tissue, is discussed as a result of (A) the infiltration of immune cells into the joints, (B) an altered homeostasis of the joint cavity (synovium) with a critical role of bone remodeling cells, and (C) release of inflammatory factors including adipokines in the arthritic joint. In addition to the classical medication, low-dose radiation therapy using photons or radon spa treatments has shown to reduce pain and improve the mobility of the patients. However, the cellular and molecular mechanisms of anti-inflammatory effects of radon are yet poorly understood. We analyzed blood and serum samples from 32 patients, suffering from MSDs, who had been treated in the radon spa in Bad Steben (Germany). Before and after therapy, we measured the levels of markers related to bone metabolism (collagen fragments type-1, cartilage oligomeric matrix protein, receptor activator of NFκB ligand, and osteoprotegerin) in the serum of patients. In addition, adipokines related to inflammation (visfatin, leptin, resistin, and adiponectin) were analyzed. Some of these factors are known to correlate with disease activity. Since T cells play an important role in the progression of the disease, we further analyzed in blood samples the frequency of pro- and anti-inflammatory T cell subpopulations (CD4+IL17+ T cells and CD4+FoxP3+ regulatory T cells). Overall, we found a decrease of collagen fragments (CTX-I), indicating decreased bone resorption, presumably by osteoclasts, in the serum of MSD patients. We also observed reduced levels of visfatin and a consistent trend toward an increase of regulatory T cells in the peripheral blood, both indicating attenuation of inflammation. However, key proteins of bone metabolism

  7. Decrease of Markers Related to Bone Erosion in Serum of Patients with Musculoskeletal Disorders after Serial Low-Dose Radon Spa Therapy.

    PubMed

    Cucu, Aljona; Shreder, Kateryna; Kraft, Daniela; Rühle, Paul Friedrich; Klein, Gerhart; Thiel, Gerhard; Frey, Benjamin; Gaipl, Udo S; Fournier, Claudia

    2017-01-01

    Musculoskeletal disorders (MSDs) are the most frequent cause of disability in Europe. Reduced mobility and quality of life of the patients are often associated with pain due to chronic inflammation. The inflammatory process, accompanied by a destruction of the cartilage and bone tissue, is discussed as a result of (A) the infiltration of immune cells into the joints, (B) an altered homeostasis of the joint cavity (synovium) with a critical role of bone remodeling cells, and (C) release of inflammatory factors including adipokines in the arthritic joint. In addition to the classical medication, low-dose radiation therapy using photons or radon spa treatments has shown to reduce pain and improve the mobility of the patients. However, the cellular and molecular mechanisms of anti-inflammatory effects of radon are yet poorly understood. We analyzed blood and serum samples from 32 patients, suffering from MSDs, who had been treated in the radon spa in Bad Steben (Germany). Before and after therapy, we measured the levels of markers related to bone metabolism (collagen fragments type-1, cartilage oligomeric matrix protein, receptor activator of NFκB ligand, and osteoprotegerin) in the serum of patients. In addition, adipokines related to inflammation (visfatin, leptin, resistin, and adiponectin) were analyzed. Some of these factors are known to correlate with disease activity. Since T cells play an important role in the progression of the disease, we further analyzed in blood samples the frequency of pro- and anti-inflammatory T cell subpopulations (CD4(+)IL17(+) T cells and CD4(+)FoxP3(+) regulatory T cells). Overall, we found a decrease of collagen fragments (CTX-I), indicating decreased bone resorption, presumably by osteoclasts, in the serum of MSD patients. We also observed reduced levels of visfatin and a consistent trend toward an increase of regulatory T cells in the peripheral blood, both indicating attenuation of inflammation. However, key proteins of bone

  8. Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cells.

    PubMed

    Tchernychev, Boris; Ren, Yong; Sachdev, Pallavi; Janz, Jay M; Haggis, Lynn; O'Shea, Adam; McBride, Ed; Looby, Richard; Deng, Qing; McMurry, Thomas; Kazmi, Manija A; Sakmar, Thomas P; Hunt, Stephen; Carlson, Kenneth E

    2010-12-21

    The G protein-coupled receptor (GPCR), chemokine CXC-type receptor 4 (CXCR4), and its ligand, CXCL12, mediate the retention of polymorphonuclear neutrophils (PMNs) and hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Agents that disrupt CXCL12-mediated chemoattraction of CXCR4-expressing cells mobilize PMNs and HSPCs into the peripheral circulation and are therapeutically useful for HSPC collection before autologous bone marrow transplantation (ABMT). Our aim was to develop unique CXCR4-targeted therapeutics using lipopeptide GPCR modulators called pepducins. A pepducin is a synthetic molecule composed of a peptide derived from the amino acid sequence of one of the intracellular (IC) loops of a target GPCR coupled to a lipid tether. We prepared and screened a small CXCR4-targeted pepducin library and identified several pepducins with in vitro agonist activity, including ATI-2341, whose peptide sequence derives from the first IC loop. ATI-2341 induced CXCR4- and G protein-dependent signaling, receptor internalization, and chemotaxis in CXCR4-expressing cells. It also induced dose-dependent peritoneal recruitment of PMNs when administered i.p. to mice. However, when administered systemically by i.v. bolus, ATI-2341 acted as a functional antagonist and dose-dependently mediated release of PMNs from the bone marrow of both mice and cynomolgus monkeys. ATI-2341-mediated release of granulocyte/macrophage progenitor cells from the bone marrow was confirmed by colony-forming assays. We conclude that ATI-2341 is a potent and efficacious mobilizer of bone marrow PMNs and HSPCs and could represent a previously undescribed therapeutic approach for the recruitment of HSPCs before ABMT.

  9. Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study.

    PubMed

    Casazza, K; Hanks, L J; Hidalgo, B; Hu, H H; Affuso, O

    2012-01-01

    Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 min of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after 10 weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest that physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization.

  10. Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven bone formation.

    PubMed

    Sun, Yong-Xin; Li, Lei; Corry, Kylie A; Zhang, Pei; Yang, Yang; Himes, Evan; Mihuti, Cristina Layla; Nelson, Cecilia; Dai, Guoli; Li, Jiliang

    2015-05-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts. Nrf2 has been considered a master regulator of cytoprotective genes against oxidative and chemical insults. The lack of Nrf2 can induce pathologies in multiple organs. The aim of this study was to investigate the role of Nrf2 in load-driven bone metabolism using Nrf2 knockout (KO) mice. Compared to age-matched littermate wild-type controls, Nrf2 KO mice have significantly lowered femoral bone mineral density (-7%, p<0.05), bone formation rate (-40%, p<0.05), as well as ultimate force (-11%, p<0.01). The ulna loading experiment showed that Nrf2 KO mice were less responsive than littermate controls, as indicated by reduction in relative mineralizing surface (rMS/BS, -69%, p<0.01) and relative bone formation rate (rBFR/BS, -84%, p<0.01). Furthermore, deletion of Nrf2 suppressed the load-driven gene expression of antioxidant enzymes and Wnt5a in cultured primary osteoblasts. Taken together, the results suggest that the loss-of-function mutation of Nrf2 in bone impairs bone metabolism and diminishes load-driven bone formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Role of macrophages in mobilization of hematopoietic progenitor cells from bone marrow after hemorrhagic shock.

    PubMed

    Xiang, Meng; Yuan, Youzhong; Fan, Liyan; Li, Yuehua; Li, Aijun; Yin, Lianhua; Scott, Melanie J; Xiao, Guozhi; Billiar, Timothy R; Wilson, Mark A; Fan, Jie

    2012-05-01

    The release of hematopoietic progenitor cells (HPCs) from bone marrow (BM) is under tight homeostatic control. Under stress conditions, HPCs migrate from BM and egress into circulation to participate in immune response, wound repair, or tissue regeneration. Hemorrhagic shock with resuscitation (HS/R), resulting from severe trauma and major surgery, promotes HPC mobilization from BM, which, in turn, affects post-HS immune responses. In this study, we investigated the mechanism of HS/R regulation of HPC mobilization from BM. Using a mouse HS/R model, we demonstrate that the endogenous alarmin molecule high-mobility group box 1 mediates HS/R-induced granulocyte colony-stimulating factor secretion from macrophages (Mϕ in a RAGE [receptor for advanced glycation end products] signaling-dependent manner. Secreted granulocyte colony-stimulating factor, in turn, induces HPC egress from BM. We also show that activation of β-adrenergic receptors on Mϕ by catecholamine mediates the HS/R-induced release of high-mobility group box 1. These data indicate that HS/R, a global ischemia-reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuroendocrine and innate immune systems, in which Mϕ play a central role.

  12. Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect against cerebral ischemia/reperfusion injury.

    PubMed

    Miao, Ming-San; Guo, Lin; Li, Rui-Qi; Ma, Xiao

    2016-02-01

    Previous studies have shown that Radix Ilicis Pubescentis total flavonoids have a neuroprotective effect, but it remains unclear whether Radix Ilicis Pubescentis total flavonoids have a synergistic effect with the recombinant human granulocyte colony stimulating factor-mobilized bone marrow stem cell transplantation on cerebral ischemia/reperfusion injury. Rat ischemia models were administered 0.3, 0.15 and 0.075 g/kg Radix Ilicis Pubescentis total flavonoids from 3 days before modeling to 2 days after injury. Results showed that Radix Ilicis Pubescentis total flavonoids could reduce pathological injury in rats with cerebral ischemia/reperfusion injury. The number of Nissl bodies increased, Bax protein expression decreased, Bcl-2 protein expression increased and the number of CD34-positive cells increased. Therefore, Radix Ilicis Pubescentis total flavonoids can improve the bone marrow stem cell mobilization effect, enhance the anti-apoptotic ability of nerve cells, and have a neuroprotective effect on cerebral ischemia/reperfusion injury in rats.

  13. Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis.

    PubMed

    Morony, S; Capparelli, C; Sarosi, I; Lacey, D L; Dunstan, C R; Kostenuik, P J

    2001-06-01

    Certain malignancies, including breast cancer, frequently metastasize to bone, where the tumor cells induce osteoclasts to locally destroy bone. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, is a negative regulator of osteoclast differentiation, activation, and survival. We tested the ability of recombinant OPG to inhibit tumor-induced osteoclastogenesis, osteolysis, and skeletal tumor burden in two animal models. In a syngeneic model, mouse colon adenocarcinoma (Colon-26) cells were injected into the left ventricle of mice. Treatment with OPG dose-dependently decreased the number and area of radiographically evident lytic bone lesions, which, at the highest dose, were undetectable. Histologically, OPG also decreased skeletal tumor burden and tumor-associated osteoclasts. In a nude mouse model, OPG treatment completely prevented radiographic osteolytic lesions caused by human MDA-MB-231 breast cancer cells. Histologically, OPG decreased skeletal tumor burden by 75% and completely eradicated MDA tumor-associated osteoclasts. In both models, OPG had no effect on metastatic tumor burden in a panel of soft tissue organs. These data indicate that OPG may be an effective therapy for preventing osteolysis and decreasing skeletal tumor burden in patients with bone metastasis.

  14. Influence of muscle mass and bone mass on the mobility of elderly women: an observational study

    PubMed Central

    2014-01-01

    Background The purpose of this study was to investigate the influence of muscle mass and bone mineral density on markers of mobility in dwelling elderly women. Methods This cross-sectional study included 99 elderly women, who were 65 years old or above, in Campinas-SP, Brazil. To collect data, we used sociodemographic data, the body mass index (BMI), health status, comorbidities, use of medications, mobility tests (TUG and gait speed) and examinations of the body composition (densitometry with dual-emission X-ray absorptiometry “DXA”). In order to examine the relationship between muscle and bone mass with mobility (gait speed and TUG), we applied the Spearman correlation coefficient. Also was applied the analysis of covariance (ANCOVA) adjusted for age and comorbidities. To identify the factors associated with mobility, we used the univariate and multivariate logistic regression analysis. The level of significance for statistical tests was P < 0.05. Results The correlation between sarcopenia and bone mineral density with mobility tests showed a significant relationship only between sarcopenia and TUG (r = 0.277, P = 0.006) in Spearman correlation coefficient. The result of the correlation analysis (ANCOVA) showed that sarcopenia was associated with gait speed (r2 = 0.0636, P = 0.0018) and TUG (r2 = 0.0898, P = 0.0027). The results of the multivariate analysis showed that age (P = 0.034, OR = 1.081) was associated with worse performance on gait speed. By highlighting the TUG test, the results of the multivariate analysis showed that the age (P = 0.004, OR = 1.111) and BMI in overweight (P = 0.011, OR = 7.83) and obese (P < 0.001, OR = 7.84) women were associated with lower performance of the functionality of the lower limbs. Conclusion The findings with regard to mobility tests which were analyzed in this study indicate the association of variables related to the aging process that contribute to the

  15. Low back pain and kidney mobility: local osteopathic fascial manipulation decreases pain perception and improves renal mobility.

    PubMed

    Tozzi, P; Bongiorno, D; Vitturini, C

    2012-07-01

    a) To calculate and compare a Kidney Mobility Score (KMS) in asymptomatic and Low Back Pain (LBP) individuals through real-time Ultrasound (US) investigation. b) To assess the effect of Osteopathic Fascial Manipulation (OFM), consisting of Still Technique (ST) and Fascial Unwinding (FU), on renal mobility in people with non-specific LBP. c) To evaluate 'if' and 'to what degree' pain perception may vary in patients with LBP, after OFM is applied. 101 asymptomatic people (F 30; M 71; mean age 38.9 ± 8) were evaluated by abdominal US screening. The distance between the superior renal pole of the right kidney and the ipsilateral diaphragmatic pillar was calculated in both maximal expiration (RdE) and maximal inspiration (RdI). The mean of the RdE-RdI ratios provided a Kidney Mobility Score (KMS) in the cohort of asymptomatic people. The same procedure was applied to 140 participants (F 66; M 74; mean age 39.3 ± 8) complaining of non-specific LBP: 109 of whom were randomly assigned to the Experimental group and 31 to the Control group. For both groups, a difference of RdE and RdI values was calculated (RD = RdE-RdI), before (RD-T0) and after (RD-T1) treatment was delivered, to assess the effective range of right kidney mobility. A blind assessment of each patient was carried using US screening. Both groups completed a Short-Form McGill Pain Assessment Questionnaire (SF-MPQ) on the day of recruitment (SF-MPQ T0) as well as on the third day following treatment (SF-MPQ T1). An Osteopathic assessment of the thoraco-lumbo-pelvic region to all the Experimental participants was performed, in order to identify specific areas of major myofascial tension. Each individual of the Experimental group received OFM by the same Osteopath who had previously assessed them. A sham-treatment was applied to the Control group for the equivalent amount of time. a) The factorial ANOVA test showed a significant difference (p-value < 0.05) between KMS in asymptomatic individuals (1.92

  16. Human short-term exposure to electromagnetic fields emitted by mobile phones decreases computer-assisted visual reaction time.

    PubMed

    Mortazavi, S M J; Rouintan, M S; Taeb, S; Dehghan, N; Ghaffarpanah, A A; Sadeghi, Z; Ghafouri, F

    2012-06-01

    The worldwide dramatic increase in mobile phone use has generated great concerns about the detrimental effects of microwave radiations emitted by these communication devices. Reaction time plays a critical role in performing tasks necessary to avoid hazards. As far as we know, this study is the first survey that reports decreased reaction time after exposure to electromagnetic fields generated by a high specific absorption rate mobile phone. It is also the first study in which previous history of mobile phone use is taken into account. The aim of this study was to assess both the acute and chronic effects of electromagnetic fields emitted by mobile phones on reaction time in university students. Visual reaction time (VRT) of young university students was recorded with a simple blind computer-assisted-VRT test, before and after a 10 min real/sham exposure to electromagnetic fields of mobile phones. Participants were 160 right-handed university students aged 18-31. To assess the effect of chronic exposures, the reaction time in sham-exposed phases were compared among low level, moderate and frequent users of mobile phones. The mean ± SD reaction time after real exposure and sham exposure were 286.78 ± 31.35 ms and 295.86 ± 32.17 ms (P < 0.001), respectively. The age of students did not significantly alter the reaction time either in talk or in standby mode. The reaction time either in talk or in standby mode was shorter in male students. The students' VRT was significantly affected by exposure to electromagnetic fields emitted by a mobile phone. It can be concluded that these exposures cause decreased reaction time, which may lead to a better response to different hazards. In this light, this phenomenon might decrease the chances of human errors and fatal accidents.

  17. Electromagnetic Radiofrequency Radiation Emitted from GSM Mobile Phones Decreases the Accuracy of Home Blood Glucose Monitors.

    PubMed

    Mortazavi, Smj; Gholampour, M; Haghani, M; Mortazavi, G; Mortazavi, Ar

    2014-09-01

    Mobile phones are two-way radios that emit electromagnetic radiation in microwave range. As the number of mobile phone users has reached 6 billion, the bioeffects of exposure to mobile phone radiation and mobile phone electromagnetic interference with electronic equipment have received more attention, globally. As self-monitoring of blood glucose can be a beneficial part of diabetes control, home blood glucose testing kits are very popular. The main goal of this study was to investigate if radiofrequency radiation emitted from a common GSM mobile phone can alter the accuracy of home blood glucose monitors. Forty five female nondiabetic students aged 17-20 years old participated in this study. For Control-EMF group (30 students), blood glucose concentration for each individual was measured in presence and absence of radiofrequency radiation emitted by a common GSM mobile phone (HTC touch, Diamond 2) while the phone was ringing. For Control- Repeat group (15 students), two repeated measurements were performed for each participant in the absence of electromagnetic fields. The magnitude of the changes between glucose levels in two repeated measurements (|ΔC|) in Control-Repeat group was 1.07 ± 0.88 mg/dl while this magnitude for Control-EMF group was 7.53 ± 4.76 mg/dl (P < 0.001, two-tailed test). To the best of our knowledge, this is the first study to assess the electromagnetic interference in home blood glucose monitors. It can be concluded that electromagnetic interference from mobile phones has an adverse effect on the accuracy of home blood glucose monitors. We suggest that mobile phones should be used at least 50 cm away from home blood glucose monitors.

  18. Electromagnetic Radiofrequency Radiation Emitted from GSM Mobile Phones Decreases the Accuracy of Home Blood Glucose Monitors

    PubMed Central

    Mortazavi, SMJ; Gholampour, M; Haghani, M; Mortazavi, G; Mortazavi, AR

    2014-01-01

    Mobile phones are two-way radios that emit electromagnetic radiation in microwave range. As the number of mobile phone users has reached 6 billion, the bioeffects of exposure to mobile phone radiation and mobile phone electromagnetic interference with electronic equipment have received more attention, globally. As self-monitoring of blood glucose can be a beneficial part of diabetes control, home blood glucose testing kits are very popular. The main goal of this study was to investigate if radiofrequency radiation emitted from a common GSM mobile phone can alter the accuracy of home blood glucose monitors. Forty five female nondiabetic students aged 17-20 years old participated in this study. For Control-EMF group (30 students), blood glucose concentration for each individual was measured in presence and absence of radiofrequency radiation emitted by a common GSM mobile phone (HTC touch, Diamond 2) while the phone was ringing. For Control- Repeat group (15 students), two repeated measurements were performed for each participant in the absence of electromagnetic fields. The magnitude of the changes between glucose levels in two repeated measurements (|ΔC|) in Control-Repeat group was 1.07 ± 0.88 mg/dl while this magnitude for Control-EMF group was 7.53 ± 4.76 mg/dl (P < 0.001, two-tailed test). To the best of our knowledge, this is the first study to assess the electromagnetic interference in home blood glucose monitors. It can be concluded that electromagnetic interference from mobile phones has an adverse effect on the accuracy of home blood glucose monitors. We suggest that mobile phones should be used at least 50 cm away from home blood glucose monitors. PMID:25505778

  19. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    PubMed Central

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  20. Self-reported Sitting Time is Associated With Decreased Mobility in Older Adults.

    PubMed

    Yen, Chi-Hua; Ku, Ming-Hsiang; Wang, Ching-Yi

    Prolonged sitting is associated with increased risk of sarcopenia in community-dwelling older adults and can lead to poor muscle function, limited balance and transfer abilities, and mobility limitations. Sitting time can be a modifiable factor in preserving independent mobility in older adults. Assessing sitting time is an important measure for preventive medicine in older populations. The purposes of this study were to examine the test-retest reliability of older adults' reported (using a recall strategy) sitting time and to determine its association with mobility limitation. In this cross-sectional study, 140 older adults aged 65 years or more from community centers were assessed for their sitting time and mobility limitation. A week later, 86 participants returned for the retest of sitting time. The test-retest reliability of the reported (recall strategy) measure of sitting time was examined by intraclass correlation coefficient (ICC), and its association with mobility limitation was examined by logistic regression analysis adjusted for age. The reported measure (recall strategy) of sitting time showed good test-retest reliability (ICC = 0.85). The results of logistic regression analysis indicated that sitting time was associated with mobility limitation, adjusted for age. Older adults' reported (recall strategy) sitting time had good test-retest reliability (ICC(2,1) = 0.85). The reported measure (recall strategy) seems to have yielded consistent reporting. The association of prolonged sitting time with mobility limitation needs to be substantiated in a future longitudinal study to determine whether a causality relationship exists. Sitting time in older adults can be reliably measured with a reported measure (a recall strategy) over a 1-week interval. Older adults who spend more time sitting are more likely to experience mobility limitation.

  1. Decreased osteogenic differentiation of mesenchymal stem cells and reduced bone mineral density in patients with adolescent idiopathic scoliosis.

    PubMed

    Park, Weon Wook; Suh, Kuen Tak; Kim, Jeung Il; Kim, Seong-Jang; Lee, Jung Sub

    2009-12-01

    Generalized low bone mass and osteopenia in both axial and peripheral skeletons have been reported in adolescent idiopathic scoliosis (AIS). However, the mechanism and causes of bone loss in AIS have not been identified. Therefore, this study examined the relationship between the osteogenic and adipogenic differentiation abilities of mesenchymal stem cells (MSCs) and bone mass in 19 patients with AIS and compared these with those of 16 age- and gender-matched patients with lower leg fracture. Mean lumbar spinal bone mineral density (LSBMD) in AIS patients was found to be lower than in controls (P = 0.037) and the osteogenic differentiation abilities and alkaline phosphatase activities of MSCs from patients were also found to be lower than those of controls (P = 0.0073 and P = 0.001, respectively), but the abilities of the MSCs of patients and controls to undergo adipogenic differentiation were similar. The osteogenic differentiation ability was found to be positively correlated with alkaline phosphatase activity in the AIS group. However, the osteogenic and adipogenic abilities were not found to be correlated with LSBMD in either patients or controls. These findings suggest that the decreased osteogenic differentiation ability of MSCs might be one of the possible mechanisms leading to low bone mass in AIS. However, we did not determine definite mechanisms of low bone mass in AIS. Therefore, further study with large scale will be needed to identify the mechanism involved.

  2. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip BMD induced by weight loss despite decline in bone-active hormones*

    PubMed Central

    Shah, Krupa; Armamento-Villareal, Reina; Parimi, Nehu; Chode, Suresh; Sinacore, David R.; Hilton, Tiffany N.; Napoli, Nicola; Qualls, Clifford; Villareal, Dennis T.

    2011-01-01

    Weight-loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight-loss therapy should include an intervention to minimize bone loss such as exercise training (ET). The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 yrs) obese (BMI ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group P<.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group P<.001) Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%) while they decreased in the exercise group (−13% and −15%) (between-group P<.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (P=.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%) and diet-exercise (−38% and −13%) groups, not in the exercise and control groups (between-group P=.001). Multivariate analyses revealed that changes in lean body mass (β=.33), serum osteocalcin (β= −.24), and 1-RM strength (β=.23) were independent predictors of changes in hip BMD (all P<.05). In conclusion, the addition of ET to weight-loss therapy among obese older adults prevents weight-loss-induced increase in bone turnover and attenuates

  3. Heme oxygenase-1 attenuates acute pulmonary inflammation by decreasing the release of segmented neutrophils from the bone marrow.

    PubMed

    Konrad, Franziska M; Braun, Stefan; Ngamsri, Kristian-Christos; Vollmer, Irene; Reutershan, Jörg

    2014-11-01

    Recruiting polymorphonuclear neutrophil granulocytes (PMNs) from circulation and bone marrow to the site of inflammation is one of the pivotal mechanisms of the innate immune system. During inflammation, the enzyme heme oxygenase 1 (HO-1) has been shown to reduce PMN migration. Although these effects have been described in various models, underlying mechanisms remain elusive. Recent studies revealed an influence of HO-1 on different cells of the bone marrow. We investigated the particular role of the bone marrow in terms of HO-1-dependent pulmonary inflammation. In a murine model of LPS inhalation, stimulation of HO-1 by cobalt (III) protoporphyrin-IX-chloride (CoPP) resulted in reduced segmented PMN migration into the alveolar space. In the CoPP group, segmented PMNs were also decreased intravascularly, and concordantly, mature and immature PMN populations were higher in the bone marrow. Inhibition of the enzyme by tin protoporphyrin-IX increased segmented and banded PMN migration into the bronchoalveolar lavage fluid with enhanced PMN release from the bone marrow and aggravated parameters of tissue inflammation. Oxidative burst activity was significantly higher in immature compared with mature PMNs. The chemokine stromal-derived factor-1 (SDF-1), which mediates homing of leukocytes into the bone marrow and is decreased in inflammation, was increased by CoPP. When SDF-1 was blocked by the specific antagonist AMD3100, HO-1 activation was no longer effective in curbing PMN trafficking to the inflamed lungs. In conclusion, we show evidence that the anti-inflammatory effects of HO-1 are largely mediated by inhibiting the release of segmented PMNs from the bone marrow rather than direct effects within the lung.

  4. Proximal Femur Bone Density Decreases up to 5 Years After Total Hip Arthroplasty in Young, Active Patients.

    PubMed

    Nam, Denis; Barrack, Robert L; Clohisy, John C; Nunley, Ryan M

    2016-12-01

    The number of young, active patients undergoing hip arthroplasty continues to increase. The purpose of this study was to evaluate femoral bone density over a 5-year period after hip arthroplasty in young, active patients. A total of 96 patients (103 hips) with a presymptomatic University of California at Los Angeles (UCLA) score ≥6 who had a total hip arthroplasty (THA; 45 hips) or surface replacement arthroplasty (SRA; 58 hips) were prospectively enrolled. UCLA and Harris Hip Scores were collected preoperatively and postoperatively, and dual energy X-ray absorptiometry scans were performed at 6 weeks, 6 months, 1 year, 2 years, and 5 years postoperatively. Bone density was analyzed for 7 traditional Gruen zones in both groups and 6 femoral neck zones in the SRA group. Bone density ratios were calculated for change in bone density compared with baseline. No differences were present in the preoperative or postoperative UCLA or Harris Hip Scores between the SRA and THA cohorts (P = .07-.7). In the THA group, bone density never returned to baseline during the 5-year period in Gruen zones 1 (91.2% of baseline), 2 (94.8%), 6 (97.3%), and 7 (89.2%). There were no decreases in bone mineral density ratio for the femoral Gruen zones in the SRA group at any interval. Femoral neck bone density after SRA increased on the lateral, tension side up to 5 years postoperatively (P < .0001). Young, active patients undergoing THA with cementless femoral fixation demonstrate reductions in bone density in the proximal femur in Gruen zones 1, 2, and 7 over time. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats.

    PubMed

    Brzóska, M M; Moniuszko-Jakoniuk, J

    2004-11-01

    The effects of low-level lifetime exposure to cadmium (Cd) on the skeleton mineral status and the risk of bone loss in the elderly were studied in an experimental model of human environmental exposure in non-Cd-polluted areas. Young female Wistar rats were exposed to 1 mg Cd/l in drinking water for 24 months. Bone mineral content (BMC), density (BMD) and area of the lumbar spine (L1-L5) and femur, and total skeleton BMD (T-BMD) were measured densitometrically at the baseline and after 6, 12, 18, and 24 months. Prevalence of osteopenia and osteoporosis was evaluated based on the BMD T score and Z score. Osteocalcin (OC) in the serum and total alkaline phosphatase (total ALP) in the serum, cortical and trabecular bone samples as bone formation markers, and C-terminal cross-linking telopeptide of type I collagen (CTX) in the serum and urine as bone resorption markers were measured. Calcium (Ca) and Cd concentrations in the serum/blood and urine were determined as well. In the Cd-exposed females, the L1-L5 and femur BMC and BMD at all the studied time points were lower compared to control. The exposure to Cd resulted in lower accumulation of peak bone mass, accelerated osteopenia, and enhanced the prevalence of osteoporosis in aged rats. The effect of Cd was more pronounced at the L1-L5 than at the femur. CTX concentration in the urine was decreased after 6 months and next increased compared to control, whereas the urinary loss of Ca was enhanced during the exposure to Cd. After 24 months of the treatment, the serum total ALP activity and the activity of this enzyme in cortical and trabecular bone decreased and serum CTX concentration increased, whereas the concentrations of OC and Ca were unchanged. The study clearly revealed that low-level lifetime exposure to Cd diminishes the accumulation of bone mass during skeletal growth and influences bone metabolism at maturity causing osteopenia, and enhances the age-related bone loss due to high turnover rate leading in

  6. Lead and osteoporosis: Mobilization of lead from bone in postmenopausal women

    SciTech Connect

    Silbergeld, E.K. ); Schwartz, J. ); Mahaffey, K. )

    1988-10-01

    Although it has been known that humans accumulate lead in bone, mineralized tissue has been considered primarily as a sequestering compartment and not as a site of toxic action for lead. However, experimental data indicate that bone lead can be released during conditions of demineralization, such as pregnancy and lactation. We have examined lead status in women, before and after menopause, using the NHANES II dataset compiled between 1976 and 1980. In 2981 black and white women there was a highly significant increase in both whole blood and calculated plasma lead concentrations after menopause. The results indicate that bone lead is not an inert storage site for absorbed lead. Moreover, lead may interact with other factors in the course of postmenopausal osteoporosis, to aggravate the course of the disease, since lead is known to inhibit activation of vitamin D, uptake of dietary calcium, and several regulatory aspects of bone cell function. The consequences of this mobilization may also be of importance in assessing the risks of maternal lead exposure to fetal and infant health.

  7. Involuntary wheel running improves but does not fully reverse the deterioration of bone structure of obese rats despite decreasing adiposity.

    PubMed

    Cao, Jay J; Picklo, Matthew J

    2015-08-01

    This study investigated whether exercise or antioxidant supplementation with vitamin C and E during exercise affects bone structure and markers of bone metabolism in obese rat. Sprague-Dawley rats, 6-week old, were fed a normal-fat diet (NF, 10 % kcal as fat) and a high-fat diet (HF, 45 % with extra fat from lard) ad libitum for 14 weeks. Then, rats on the high-fat diet were assigned randomly to three treatment groups for additional 12 weeks with forced exercise: HF; HF + exercise (HF + Ex); and HF with vitamin C (0.5 g ascorbate/kg diet) and vitamin E (0.4 g α-tocopherol acetate/kg diet) supplementation + exercise (HF + Ex + VCE). At the end of the study, body weight and fat (%) were similar among NF, HF + Ex, and HF + Ex + VCE, whereas HF had greater body weight and fat (%) than other groups. Compared to NF, HF had elevated serum leptin, tartrate-resistant acid phosphatase (TRAP), and IGF-1; increased trabecular separation and structural model index; and lowered bone mineral density, trabecular connectivity density, and trabecular number in distal femur, while HF + Ex and HF + Ex + VCE had elevated serum TRAP and decreased bone volume/total volume and trabecular number of distal femurs. Compared to HF, HF + Ex and HF + Ex + VCE had decreased serum TRAP and osteocalcin and improved bone structural properties of the distal femur. These findings suggest that exercise, while decreasing body fat, does not fully protect against the negative skeletal effects of existing obesity induced by a high-fat diet. Furthermore, vitamin C and E supplementation has no additional benefits on bone structural properties during exercise.

  8. Bone marrow (BM) transplantation promotes beta-cell regeneration after acute injury through BM cell mobilization.

    PubMed

    Hasegawa, Yutaka; Ogihara, Takehide; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Gao, Junhong; Kaneko, Keizo; Ishihara, Hisamitsu; Sasano, Hironobu; Nakauchi, Hiromitsu; Oka, Yoshitomo; Katagiri, Hideki

    2007-05-01

    There is controversy regarding the roles of bone marrow (BM)-derived cells in pancreatic beta-cell regeneration. To examine these roles in vivo, mice were treated with streptozotocin (STZ), followed by bone marrow transplantation (BMT; lethal irradiation and subsequent BM cell infusion) from green fluorescence protein transgenic mice. BMT improved STZ-induced hyperglycemia, nearly normalizing glucose levels, with partially restored pancreatic islet number and size, whereas simple BM cell infusion without preirradiation had no effects. In post-BMT mice, most islets were located near pancreatic ducts and substantial numbers of bromodeoxyuridine-positive cells were detected in islets and ducts. Importantly, green fluorescence protein-positive, i.e. BM-derived, cells were detected around islets and were CD45 positive but not insulin positive. Then to examine whether BM-derived cell mobilization contributes to this process, we used Nos3(-/-) mice as a model of impaired BM-derived cell mobilization. In streptozotocin-treated Nos3(-/-) mice, the effects of BMT on blood glucose, islet number, bromodeoxyuridine-positive cells in islets, and CD45-positive cells around islets were much smaller than those in streptozotocin-treated Nos3(+/+) controls. A series of BMT experiments using Nos3(+/+) and Nos3(-/-) mice showed hyperglycemia-improving effects of BMT to correlate inversely with the severity of myelosuppression and delay of peripheral white blood cell recovery. Thus, mobilization of BM-derived cells is critical for BMT-induced beta-cell regeneration after injury. The present results suggest that homing of donor BM-derived cells in BM and subsequent mobilization into the injured periphery are required for BMT-induced regeneration of recipient pancreatic beta-cells.

  9. Role of Macrophages in Mobilization of Hematopoietic Progenitor Cells from Bone Marrow after Hemorrhagic Shock

    PubMed Central

    Xiang, Meng; Yuan, Youzhong; Fan, Liyan; Li, Yuehua; Li, Aijun; Yin, Lianhua; Scott, Melanie J.; Xiao, Guozhi; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie

    2012-01-01

    The release of hematopoietic progenitor cells (HPC) from bone marrow (BM) is under tight homeostatic control. Under stress conditions, HPC migrate from BM and egress into circulation to participate in immune response, wound repair, or tissue regeneration. Hemorrhagic shock with resuscitation (HS/R), resulting from severe trauma and major surgery, promotes HPC mobilization from BM, which in turn affects post-HS immune responses. In this study, we investigated the mechanism of HS/R regulation of HPC mobilization from BM. Using a mouse HS/R model we demonstrate that the endogenous alarmin molecule high-mobility group box 1 (HMGB1) mediates HS/R-induced G-CSF secretion from macrophages (Mφ) in a RAGE signaling-dependent manner. Secreted G-CSF, in turn, induces HPC egress from BM. We also show that activation of β-adrenergic receptors on Mφ by catecholamine mediates the HS/R-induced release of HMGB1. These data indicate that HS/R, a global ischemia/reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuro-endocrine and innate immune systems, in which Mφ play a central role. PMID:22293600

  10. Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

    PubMed Central

    Alvarez, P.; Carrillo, E.; Vélez, C.; Hita-Contreras, F.; Martínez-Amat, A.; Rodríguez-Serrano, F.; Boulaiz, H.; Ortiz, R.; Melguizo, C.; Prados, J.; Aránega, A.

    2013-01-01

    Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM) and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs) cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a) the role of different factors, such as stromal cell derived factor-1 (SDF-1), granulocyte colony-stimulating factor (G-CSF), and vascular cell adhesion molecule-1 (VCAM-1), among other ligands; (b) the stem cell count in peripheral blood and BM and influential factors; (c) the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d) the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases. PMID:23844360

  11. Regulatory systems in bone marrow for hematopoietic stem/progenitor cells mobilization and homing.

    PubMed

    Alvarez, P; Carrillo, E; Vélez, C; Hita-Contreras, F; Martínez-Amat, A; Rodríguez-Serrano, F; Boulaiz, H; Ortiz, R; Melguizo, C; Prados, J; Aránega, A

    2013-01-01

    Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM) and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs) cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a) the role of different factors, such as stromal cell derived factor-1 (SDF-1), granulocyte colony-stimulating factor (G-CSF), and vascular cell adhesion molecule-1 (VCAM-1), among other ligands; (b) the stem cell count in peripheral blood and BM and influential factors; (c) the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d) the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

  12. Decreased PTH levels accompanied by low bone formation are associated with vertebral fractures in postmenopausal women with type 2 diabetes.

    PubMed

    Yamamoto, Masahiro; Yamaguchi, Toru; Nawata, Kiyoko; Yamauchi, Mika; Sugimoto, Toshitsugu

    2012-04-01

    Patients with type 2 diabetes (T2DM) have an increased risk of vertebral fractures (VF) compared with non-T2DM controls due to poor bone quality. The aim of this study was to investigate the association between VF and bone turnover. We compared clinical parameters, such as serum PTH and osteocalcin (OC), between hospital-based Japanese T2DM patients (123 postmenopausal women and 132 men over 50 yr old) and medical checkup-based non-T2DM controls (189 women and 51 men). The association between PTH and OC levels was investigated, and the VF risks were compared for four subgroups classified by PTH and OC values. T2DM patients had lower PTH and OC levels than the controls for both sexes (P < 0.01). Multivariate regression analysis showed that PTH levels of T2DM patients were significantly and positively correlated with OC levels (women, r = 0.324, P < 0.01; men, r = 0.343, P < 0.01). When participants were divided into two subgroups based on mean PTH and OC levels, the group of T2DM women with lower PTH and lower OC levels had a significantly higher risk of VF than those with higher PTH and higher OC levels after adjusting for age, body mass index, hemoglobin A(1c), creatinine, 25-hydroxyvitamin D, and lumbar bone mineral density (odds ratio, 4.73; 95% confidence interval, 1.20-18.6; P = 0.026). Patients with T2DM had decreased PTH levels. In T2DM postmenopausal women, lower PTH levels accompanied by low bone formation may elevate VF risk independently of bone mineral density compared with higher bone formation, possibly as a result of reduced bone quality.

  13. Lidocaine Concentration in Mandibular Bone After Subperiosteal Infiltration Anesthesia Decreases With Elevation of Periosteal Flap and Irrigation With Saline

    PubMed Central

    Ogawa, Sachie; Watanabe, Masahiro; Kawaai, Hiroyoshi; Tada, Hitoshi; Yamazaki, Shinya

    2014-01-01

    It has been reported that the action of infiltration anesthesia on the jawbone is attenuated significantly by elevation of the periosteal flap with saline irrigation in clinical studies; however, the reason is unclear. Therefore, the lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia was measured under several surgical conditions. The subjects were 48 rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000 epinephrine (adrenaline) was injected into the right mandibular angle and left mandibular body, respectively. Under several surgical conditions (presence or absence of periosteal flap, and presence or absence of saline irrigation), both mandibular bone samples were removed at a fixed time after subperiosteal infiltration anesthesia. The lidocaine concentration in each mandibular bone sample was measured by high-performance liquid chromatography. As a result, elevation of the periosteal flap with saline irrigation significantly decreased the lidocaine concentration in the mandibular bone. It is suggested that the anesthetic in the bone was washed out by saline irrigation. Therefore, supplemental conduction and/or general anesthesia should be utilized for long operations that include elevation of the periosteal flap with saline irrigation. PMID:24932978

  14. Unilateral chronic insufficiency of anterior cruciate ligament decreases bone mineral content and lean mass of the injured lower extremity.

    PubMed

    Takata, Shinjiro; Abbaspour, Aziz; Kashihara, Michiharu; Nakao, Shigetaka; Yasui, Natsuo

    2007-08-01

    We studied the effects of unilateral chronic anterior cruciate ligament (ACL) injury on bone size, bone mineral content (BMC), bone mineral density (BMD), soft tissue composition and muscle strength of the injured lower extremity in Japanese 21 men and 12 women aged 15 to 39 years. Bone area, BMD, BMC, lean mass and fat mass of lower extremity were measured using dual energy X-ray absorptiometry. The isometric and isokinetic muscle strength was assessed by an isokinetic machine.BMC, lean mass, circumference of the thigh and circumference of the lower leg of the injured lower extremity were significantly smaller than those of the intact lower extremity (p=0.0002, p<0.0001, p<0.0001, p=0.0131). In contrast, fat mass and %Fat of the injured lower extremity was significantly greater than that of the intact lower extremity (p=0.0301, p<0.0001). Bone area and BMD did not produce significant difference. These findings suggest that chronic insufficiency of ACL decreases BMC and lean mass of the injured lower extremity.

  15. Therapeutic effect of organic gallium on ovariectomized osteopenic rats by decreased serum minerals and increased bone mineral content.

    PubMed

    Ma, Zhaoji; Fu, Qin

    2010-03-01

    The purpose of this study was to verify the effect of organic gallium on ovariectomized osteopenic rats. Thirty Wistar female rats used were divided into three groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats with osteopenia, and (3) OVX rats with osteopenia treated with organic gallium. Treatments were performed over an 8-week period. At sacrifice, the fifth lumbar vertebral body, one tibia, one femur, and the fourth lumbar vertebrae were removed, subjected to micro-CT for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. The femoral neck was used for mechanical compression testing. Treatment with organic gallium increased bone volume in OVX animals. Organic gallium-treated animals had significant increases in trabecular and cortical thickness and bone strength. The plasma total calcium and inorganic phosphate concentrations in OVX rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with organic gallium. These data provide an important proof of concept that organic gallium may represent a powerful approach to treating or reversing severe osteoporosis in humans.

  16. Lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia decreases with elevation of periosteal flap and irrigation with saline.

    PubMed

    Ogawa, Sachie; Watanabe, Masahiro; Kawaai, Hiroyoshi; Tada, Hitoshi; Yamazaki, Shinya

    2014-01-01

    It has been reported that the action of infiltration anesthesia on the jawbone is attenuated significantly by elevation of the periosteal flap with saline irrigation in clinical studies; however, the reason is unclear. Therefore, the lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia was measured under several surgical conditions. The subjects were 48 rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000 epinephrine (adrenaline) was injected into the right mandibular angle and left mandibular body, respectively. Under several surgical conditions (presence or absence of periosteal flap, and presence or absence of saline irrigation), both mandibular bone samples were removed at a fixed time after subperiosteal infiltration anesthesia. The lidocaine concentration in each mandibular bone sample was measured by high-performance liquid chromatography. As a result, elevation of the periosteal flap with saline irrigation significantly decreased the lidocaine concentration in the mandibular bone. It is suggested that the anesthetic in the bone was washed out by saline irrigation. Therefore, supplemental conduction and/or general anesthesia should be utilized for long operations that include elevation of the periosteal flap with saline irrigation.

  17. Selenium deficiency decreases antioxidative capacity and is detrimental to bone microarchitecture in mice

    USDA-ARS?s Scientific Manuscript database

    Selenium (Se), a chemical component of selenoproteins (such as glutathione peroxidases and thioredoxin reductase), plays a major role in cellular redox status and may have beneficial effects on bone health. The deficiency of Se has been linked to increased oxidative stress with increased levels of r...

  18. Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study

    PubMed Central

    Hovi, Petteri; Andersson, Sture; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Strang-Karlsson, Sonja; Kajantie, Eero; Mäkitie, Outi

    2009-01-01

    Background Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood. Methods and Findings The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity. Conclusions Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors' Summary PMID:19707270

  19. Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

    PubMed Central

    Oestreich, Arin K.; Kamp, William M.; McCray, Marcus G.; Carleton, Stephanie M.; Karasseva, Natalia; Lenz, Kristin L.; Jeong, Youngjae; Daghlas, Salah A.; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M.; Ellersieck, Mark R.; Schulz, Laura C.; Phillips, Charlotte L.

    2016-01-01

    During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta. PMID:27821779

  20. Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats

    PubMed Central

    Martins, Conceição S.; Leitão, Renata F. C.; Costa, Deiziane V. S.; Melo, Iracema M.; Santos, Glaylton S.; Lima, Vilma; Baldim, Victor; Wong, Deysi V. T.; Bonfim, Luana E.; Melo, Cíntia B.; Brito, Gerly A. C.

    2016-01-01

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease. PMID:27116554

  1. SMAD signaling regulates CXCL12 expression in the bone marrow niche, affecting homing and mobilization of hematopoietic progenitors

    PubMed Central

    Khurana, Satish; Melacarne, Alessia; Yadak, Rana; Schouteden, Sarah; Notelaers, Tineke; Pistoni, Mariaelena; Maes, Christa; Verfaillie, Catherine M

    2014-01-01

    We recently demonstrated that ex vivo activation of SMAD-independent BMP4 signaling in hematopoietic stem/progenitor cells (HSPCs) influences their homing into the bone marrow (BM). We here assessed if alterations in BMP signaling in vivo affects adult hematopoiesis by affecting the BM niche. We demonstrate that systemic inhibition of SMAD-dependent BMP signaling by infusion of the BMP antagonist Noggin (NGN) significantly increased CXCL12 levels in BM plasma leading to enhanced homing and engraftment of transplanted HSPCs. Conversely, the infusion of BMP7 but not BMP4, resulted in decreased HSPC homing. Using ST2 cells as an in vitro model of BM niche, we found that incubation with neutralizing anti-BMP4 antibodies, NGN or dorsomorphin (DM) as well as knockdown of Smad1/5 and Bmp4, all enhanced CXCL12 production. Chromatin immunoprecipitation identified the SMAD-binding element in the CXCL12 promoter to which SMAD4 binds. When deleted, increased CXCL12 promoter activity was observed, and NGN or DM no longer affected Cxcl12 expression. Interestingly, BMP7 infusion resulted in mobilization of only short-term HSCs, likely because BMP7 affected CXCL12 expression only in osteoblasts but not in other niche components. Hence, we describe SMAD-dependent BMP signaling as a novel regulator of CXCL12 production in the BM niche, influencing HSPC homing, engraftment and mobilization. PMID:25069965

  2. Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study.

    PubMed

    Iki, Masayuki; Fujita, Yuki; Kouda, Katsuyasu; Yura, Akiko; Tachiki, Takahiro; Tamaki, Junko; Winzenrieth, Renaud; Sato, Yuho; Moon, Jong-Seong; Okamoto, Nozomi; Kurumatani, Norio

    2017-08-15

    Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. After excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. Hyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Brief report: Decreased bone mineral density as a long-term complication of teenage-onset anorexia nervosa.

    PubMed

    Wentz, Elisabet; Mellström, Dan; Gillberg, I Carina; Gillberg, Christopher; Råstam, Maria

    2007-07-01

    To follow up bone mineral density (BMD) 4 years after decreased BMD was diagnosed in adult individuals with teenage-onset anorexia nervosa (AN). In a previous study BMD was assessed in 39 individuals (36 women, 3 men) 11 years after AN onset. Decreased BMD occurred in a minority. In the present study, a 4-year follow-up of individuals with decreased BMD, 11 AN women were reassessed by using dual energy X-ray absorptiometry (DXA). Two women still had an eating disorder (ED). Eight out of eleven women met criteria for decreased BMD/osteoporosis. There was an increase in BMD of total body and lumbar spine (LS). There was a relationship between lumbar BMD and BMI. At follow-up of decreased BMD in adult women with teenage-onset of AN, there is a possibility of improvement of BMD. 2007 John Wiley & Sons, Ltd and Eating Disorders Association

  4. Decreased BMP2 signal in GIT1 knockout mice slows bone healing

    PubMed Central

    Fan, Jin; Zhou, Hao; Zuscik, Michael J.; Xie, Chao; Yin, Guoyong; Berk, Bradford C.

    2015-01-01

    Endochondral ossification, an important stage of fracture healing, is regulated by a variety of signaling pathways. Transforming growth factor b (TGFb) superfamily plays important roles and comprises TGFbs, bone morphogenetic proteins (BMPs), and growth differentiation factors. TGFbs primarily regulate cartilage formation and endochondral ossification. BMP2 shows diverse efficacy, from the formation of skeleton and extraskeletal organs to the osteogenesis and remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1 (GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by promoting bone formation and increasing the secretion of vascular endothelial growth factor. Our study examined whether GIT1 regulates fracture healing through the BMP2 signaling pathway and/or through the TGFb signaling pathway. GIT1 knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8 (pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2 stimulus. We detected no significant change in the pSmad2/3 level after TGFb1 stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on transcription via pSmad2/3 after TGFb1 stimulus. Our results indicate that GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2 expression, thus affecting endochondral ossification at the fracture site. PMID:25138700

  5. Correlation between nicotine-induced inhibition of hematopoiesis and decreased CD44 expression on bone marrow stromal cells.

    PubMed

    Khaldoyanidi, S; Sikora, L; Orlovskaya, I; Matrosova, V; Kozlov, V; Sriramarao, P

    2001-07-15

    This study demonstrates that in vivo exposure to cigarette smoke (CS) and in vitro treatment of long-term bone marrow cultures (LTBMCs) with nicotine, a major constituent of CS, result in inhibition of hematopoiesis. Nicotine treatment significantly delayed the onset of hematopoietic foci and reduced their size. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) within an adherent layer of LTBMCs was significantly reduced in cultures treated with nicotine. Although the production of nonadherent mature cells and their progenitors in nicotine-treated LTBMCs was inhibited, this treatment failed to influence the proliferation of committed hematopoietic progenitors when added into methylcellulose cultures. Bone marrow stromal cells are an integral component of the hematopoietic microenvironment and play a critical role in the regulation of hematopoietic stem cell proliferation and self-renewal. Exposure to nicotine decreased CD44 surface expression on primary bone marrow-derived fibroblastlike stromal cells and MS-5 stromal cell line, but not on hematopoietic cells. In addition, mainstream CS altered the trafficking of hematopoietic stem/progenitor cells (HSPC) in vivo. Exposure of mice to CS resulted in the inhibition of HSPC homing into bone marrow. Nicotine and cotinine treatment resulted in reduction of CD44 surface expression on lung microvascular endothelial cell line (LEISVO) and bone marrow-derived (STR-12) endothelial cell line. Nicotine treatment increased E-selectin expression on LEISVO cells, but not on STR-12 cells. These findings demonstrate that nicotine can modulate hematopoiesis by affecting the functions of the hematopoiesis-supportive stromal microenvironment, resulting in the inhibition of bone marrow seeding by LTC-ICs and interfering with stem cell homing by targeting microvascular endothelial cells.

  6. Puerarin decreases bone loss and collagen destruction in rats with ligature-induced periodontitis.

    PubMed

    Yang, X; Zhang, H; Wang, J; Zhang, Z; Li, C

    2015-12-01

    Puerarin, the most abundant isoflavonoid in kudzu root, shows various bioactivities, including bone-sparing, anti-inflammatory and antiproteinase properties. This study aimed to evaluate the effects of puerarin in a rat model of ligature-induced periodontitis. Rat models of periodontitis were developed by bilaterally placing ligatures around the first mandibular molars. Puerarin was administrated daily by gavage at doses of 100, 200 and 400 mg/kg, starting a day before the placement of ligatures. Rats were humanely killed 7 d after the induction of periodontitis. Micro-computed tomography and sirius red staining were used to evaluate alveolar bone loss and collagen destruction, respectively. Histomorphometrical analysis was used to assess the inflammatory cell infiltration. Immunohistochemistry and tartrate-resistant acid phosphatase were used to detect receptor activator of nuclear factor kappa B ligand and osteoprotegerin expressions, and osteoclast activity in the gingiva and alveolar bone. The activation of nuclear factor-kappa B, production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, glycosylation of extracellular matrix metalloproteinase inducer, and production of matrix metalloproteinase (MMP)-2 and MMP-9 in the gingiva were assessed by Western blot. Puerarin at doses of 200 and 400 mg/kg significantly reduced the alveolar bone loss compared with the vehicle group. Collagen destruction and inflammatory cell infiltration were significantly less in the puerarin-treated group (200 mg/kg) compared with that of the vehicle group. Puerarin (200 mg/kg) also reduced the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin and osteoclast activity. Western blot analysis showed that puerarin (200 mg/kg) inhibited the activation of nuclear factor-kappa B p65, which is associated with lower IL-1β and TNF-α production, and reduced the glycosylation of extracellular matrix metalloproteinase inducer, which is associated with lower

  7. Sweet taste receptor deficient mice have decreased adiposity and increased bone mass.

    PubMed

    Simon, Becky R; Learman, Brian S; Parlee, Sebastian D; Scheller, Erica L; Mori, Hiroyuki; Cawthorn, William P; Ning, Xiaomin; Krishnan, Venkatesh; Ma, Yanfei L; Tyrberg, Björn; MacDougald, Ormond A

    2014-01-01

    Functional expression of sweet taste receptors (T1R2 and T1R3) has been reported in numerous metabolic tissues, including the gut, pancreas, and, more recently, in adipose tissue. It has been suggested that sweet taste receptors in these non-gustatory tissues may play a role in systemic energy balance and metabolism. Smaller adipose depots have been reported in T1R3 knockout mice on a high carbohydrate diet, and sweet taste receptors have been reported to regulate adipogenesis in vitro. To assess the potential contribution of sweet taste receptors to adipose tissue biology, we investigated the adipose tissue phenotypes of T1R2 and T1R3 knockout mice. Here we provide data to demonstrate that when fed an obesogenic diet, both T1R2 and T1R3 knockout mice have reduced adiposity and smaller adipocytes. Although a mild glucose intolerance was observed with T1R3 deficiency, other metabolic variables analyzed were similar between genotypes. In addition, food intake, respiratory quotient, oxygen consumption, and physical activity were unchanged in T1R2 knockout mice. Although T1R2 deficiency did not affect adipocyte number in peripheral adipose depots, the number of bone marrow adipocytes is significantly reduced in these knockout animals. Finally, we present data demonstrating that T1R2 and T1R3 knockout mice have increased cortical bone mass and trabecular remodeling. This report identifies novel functions for sweet taste receptors in the regulation of adipose and bone biology, and suggests that in these contexts, T1R2 and T1R3 are either dependent on each other for activity or have common independent effects in vivo.

  8. Sweet Taste Receptor Deficient Mice Have Decreased Adiposity and Increased Bone Mass

    PubMed Central

    Simon, Becky R.; Learman, Brian S.; Parlee, Sebastian D.; Scheller, Erica L.; Mori, Hiroyuki; Cawthorn, William P.; Ning, Xiaomin; Krishnan, Venkatesh; Ma, Yanfei L.; Tyrberg, Björn; MacDougald, Ormond A.

    2014-01-01

    Functional expression of sweet taste receptors (T1R2 and T1R3) has been reported in numerous metabolic tissues, including the gut, pancreas, and, more recently, in adipose tissue. It has been suggested that sweet taste receptors in these non-gustatory tissues may play a role in systemic energy balance and metabolism. Smaller adipose depots have been reported in T1R3 knockout mice on a high carbohydrate diet, and sweet taste receptors have been reported to regulate adipogenesis in vitro. To assess the potential contribution of sweet taste receptors to adipose tissue biology, we investigated the adipose tissue phenotypes of T1R2 and T1R3 knockout mice. Here we provide data to demonstrate that when fed an obesogenic diet, both T1R2 and T1R3 knockout mice have reduced adiposity and smaller adipocytes. Although a mild glucose intolerance was observed with T1R3 deficiency, other metabolic variables analyzed were similar between genotypes. In addition, food intake, respiratory quotient, oxygen consumption, and physical activity were unchanged in T1R2 knockout mice. Although T1R2 deficiency did not affect adipocyte number in peripheral adipose depots, the number of bone marrow adipocytes is significantly reduced in these knockout animals. Finally, we present data demonstrating that T1R2 and T1R3 knockout mice have increased cortical bone mass and trabecular remodeling. This report identifies novel functions for sweet taste receptors in the regulation of adipose and bone biology, and suggests that in these contexts, T1R2 and T1R3 are either dependent on each other for activity or have common independent effects in vivo. PMID:24466105

  9. Sclerostin Immunoreactivity Increases in Cortical Bone Osteocytes and Decreases in Articular Cartilage Chondrocytes in Aging Mice.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W

    2016-03-01

    Sclerostin is a 24-kDa secreted glycoprotein that has been identified as a negative modulator of new bone formation and may play a major role in age-related decline in skeletal function. Although serum levels of sclerostin markedly increase with age, relatively little is known about whether cells in the skeleton change their expression of sclerostin with aging. Using immunohistochemistry and confocal microscopy, we explored sclerostin immunoreactivity (sclerostin-IR) in the femurs of 4-, 9-, and 24-month-old adult C3H/HeJ male mice. In the femur, the only two cell types that expressed detectable levels of sclerostin-IR were bone osteocytes and articular cartilage chondrocytes. At three different sites along the diaphysis of the femur, only a subset of osteocytes expressed sclerostin-IR and the percentage of osteocytes that expressed sclerostin-IR increased from approximately 36% to 48% in 4- vs. 24-month-old mice. In marked contrast, in the same femurs, there were ~40% fewer hypertrophic chondrocytes of articular cartilage that expressed sclerostin-IR when comparing 24- vs. 4-month-old mice. Understanding the mechanism(s) that drive these divergent changes in sclerostin-IR may provide insight into understanding and treating the age-related decline of the skeleton. © 2016 The Histochemical Society.

  10. Sclerostin Immunoreactivity Increases in Cortical Bone Osteocytes and Decreases in Articular Cartilage Chondrocytes in Aging Mice

    PubMed Central

    Thompson, Michelle L.; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W.

    2015-01-01

    Sclerostin is a 24-kDa secreted glycoprotein that has been identified as a negative modulator of new bone formation and may play a major role in age-related decline in skeletal function. Although serum levels of sclerostin markedly increase with age, relatively little is known about whether cells in the skeleton change their expression of sclerostin with aging. Using immunohistochemistry and confocal microscopy, we explored sclerostin immunoreactivity (sclerostin-IR) in the femurs of 4-, 9-, and 24-month-old adult C3H/HeJ male mice. In the femur, the only two cell types that expressed detectable levels of sclerostin-IR were bone osteocytes and articular cartilage chondrocytes. At three different sites along the diaphysis of the femur, only a subset of osteocytes expressed sclerostin-IR and the percentage of osteocytes that expressed sclerostin-IR increased from approximately 36% to 48% in 4- vs. 24-month-old mice. In marked contrast, in the same femurs, there were ~40% fewer hypertrophic chondrocytes of articular cartilage that expressed sclerostin-IR when comparing 24- vs. 4-month-old mice. Understanding the mechanism(s) that drive these divergent changes in sclerostin-IR may provide insight into understanding and treating the age-related decline of the skeleton. PMID:26701970

  11. Poor Compliance to Hormone Therapy and Decreased Bone Mineral Density in Women with Premature Ovarian Insufficiency

    PubMed Central

    Bachelot, Anne; Nicolas, Carole; Gricourt, Solenne; Dulon, Jérôme; Leban, Monique; Golmard, Jean Louis; Touraine, Philippe

    2016-01-01

    Premature ovarian insufficiency leads to through infertility and estrogen deficiency. Optimal management encompasses estrogen replacement therapy. Long-term outcome of women with POI is not known. We design a study to evaluate the medical care, hormone replacement therapy compliance and bone mineral density (BMD) in POI women with at least a five-year follow-up after the first evaluation. One hundred and sixty-two patients (37.3±8.0 years) were evaluated (follow-up 7.9±2.8 years). Sixty-nine patients (42.6%) had stopped their hormone replacement therapy (HRT) for at least one year during the follow up period. BMD determination at initial evaluation and at follow-up visit was completed in 92 patients. At first evaluation, 28 patients (30%) had osteopenia and 7 (8%) had osteoporosis. At follow up, 31 women (34%) had BMD impairment with osteopenia in 61% and osteoporosis in 5%. In univariate analysis and multivariate analysis, there was a significant loss of femoral BMD in women who had stopped their HRT for over a year. In conclusion, this first study concerning long-term follow-up of POI patients shows the poor compliance to their HRT, despite its importance in the prevention of bone demineralization. This study reinforces the need for follow up and specific care for POI women. PMID:27906970

  12. A Schelling model with switching agents: decreasing segregation via random allocation and social mobility

    NASA Astrophysics Data System (ADS)

    Hazan, Aurélien; Randon-Furling, Julien

    2013-10-01

    We study the behaviour of a Schelling-class system in which a fraction f of spatially-fixed switching agents is introduced. This new model allows for multiple interpretations, including: (i) random, non-preferential allocation (e.g. by housing associations) of given, fixed sites in an open residential system, and (ii) superimposition of social and spatial mobility in a closed residential system. We find that the presence of switching agents in a segregative Schelling-type dynamics can lead to the emergence of intermediate patterns (e.g. mixture of patches, fuzzy interfaces) as the ones described in [E. Hatna, I. Benenson, J. Artif. Soc. Social. Simul. 15, 6 (2012)]. We also investigate different transitions between segregated and mixed phases both at f = 0 and along lines of increasing f, where the nature of the transition changes.

  13. VEGFR2-mediated vascular dilation as a mechanism of VEGF-induced anemia and bone marrow cell mobilization.

    PubMed

    Lim, Sharon; Zhang, Yin; Zhang, Danfang; Chen, Fang; Hosaka, Kayoko; Feng, Ninghan; Seki, Takahiro; Andersson, Patrik; Li, Jingrong; Zang, Jingwu; Sun, Baocun; Cao, Yihai

    2014-10-23

    Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1(TK-/-)) did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1(+)/VEGFR2(+) populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy.

  14. G-CSF for mobilizing transplanted bone marrow stem cells in rat model of Parkinson's disease.

    PubMed

    Safari, Manouchehr; Jafari, Behnaz; Zarbakhsh, Sam; Sameni, Hamidreza; Vafaei, Abbas Ali; Mohammadi, Nasrin Khan; Ghahari, Laya

    2016-12-01

    Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc). G-CSF (70 µg/kg/day) was given from the 7(th) day after lesion for five days. The BMSCs (2×10(5)) were injected through the dorsal tail vein on the 7(th) day after lesion. The number of rotations was significantly lower in the stem cell therapy group than in the control group. In the third test in the received G-CSF and G-CSF+stem cells groups, animals displayed significant behavioral recovery compared with the control group (P<0.05). There was a significant difference in the average of dopaminergic neurons in SNpc between the control group and G-CSF and G-CS+stem cells groups. We didn't detect any labeling stem cells in SNpc. G-CSF can't mobilize low amounts of exogenous BMSCs from the blood stream to injured SNpc. But G-CSF (70 µg/kg) is more neuroprotective than BMSCs (2×10(5) number[w1] of BMSCs). Results of our study suggest that G-CSF alone is more neuroprotective than BMSCs.

  15. Hypothalamic Suppression Decreases Bone Strength Before and After Puberty in a Rat Model

    PubMed Central

    Saine, McKayla Elle; Joshi, Rupali

    2013-01-01

    The incidence of menstrual irregularities, both primary and secondary amenorrhea, has been reported to be as high as 60%, with the highest incidence in younger athletes, suggesting possible adverse effects on bone development. It was hypothesized that in a rat model, suppressed hypothalamic activity via a gonadotropin-releasing hormone antagonist (GnRH-a) before onset of puberty would result in a relatively larger bone strength deficit compared with suppression after puberty. Hypothalamic suppression was achieved by providing GnRH injections. Animals received injections for 25 days either before puberty (pre group) (age 23–46 days) or after puberty (post group) (age 65–90 days). Body weights and uterine weights were measured. Serum estradiol was assayed. Mechanical strength of the right femora and histomorphometry of the left femur were measured. Suppression of the hypothalamic– pituitary–gonadal axis was confirmed by significant atrophy of uterine tissue and suppressed estradiol levels. The peak moment was significantly lower in the pre and post GnRH-a groups compared with control. The percentage difference of the average peak moment and stiffness values from the respective age-matched control groups yielded a greater percentage difference in the pre group. The cortical area was less in the GnRH-a-treated groups, but no significant difference between the relative deficits between pre and post groups were found. Hypothalimic–pituitary–gonadal axis suppression before puberty resulted in a significantly larger deficit in mechanical strength compared with postpubertal animals. The time before puberty may represent a time when skeletal strength is more compromised. Women experience both primary and secondary amenorrhea; however, the treatment may need to be different for each condition. PMID:19350192

  16. Hypothalamic suppression decreases bone strength before and after puberty in a rat model.

    PubMed

    Yingling, Vanessa; Elle Saine, McKayla; Joshi, Rupali

    2009-06-01

    The incidence of menstrual irregularities, both primary and secondary amenorrhea, has been reported to be as high as 60%, with the highest incidence in younger athletes, suggesting possible adverse effects on bone development. It was hypothesized that in a rat model, suppressed hypothalamic activity via a gonadotropin-releasing hormone antagonist (GnRH-a) before onset of puberty would result in a relatively larger bone strength deficit compared with suppression after puberty. Hypothalamic suppression was achieved by providing GnRH injections. Animals received injections for 25 days either before puberty (pre group) (age 23-46 days) or after puberty (post group) (age 65-90 days). Body weights and uterine weights were measured. Serum estradiol was assayed. Mechanical strength of the right femora and histomorphometry of the left femur were measured. Suppression of the hypothalamic-pituitary-gonadal axis was confirmed by significant atrophy of uterine tissue and suppressed estradiol levels. The peak moment was significantly lower in the pre and post GnRH-a groups compared with control. The percentage difference of the average peak moment and stiffness values from the respective age-matched control groups yielded a greater percentage difference in the pre group. The cortical area was less in the GnRH-a-treated groups, but no significant difference between the relative deficits between pre and post groups were found. Hypothalamic-pituitary-gonadal axis suppression before puberty resulted in a significantly larger deficit in mechanical strength compared with postpubertal animals. The time before puberty may represent a time when skeletal strength is more compromised. Women experience both primary and secondary amenorrhea; however, the treatment may need to be different for each condition.

  17. Hematopoietic cytokines for cardiac repair: mobilization of bone marrow cells and beyond

    PubMed Central

    Sanganalmath, Santosh K.; Abdel-Latif, Ahmed; Bolli, Roberto; Xuan, Yu-Ting

    2014-01-01

    Hematopoietic cytokines, traditionally known to influence cellular proliferation, differentiation, maturation, and lineage commitment in the bone marrow, include granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor, stem cell factor, Flt-3 ligand, and erythropoietin among others. Emerging evidence suggests that these cytokines also exert multifarious biological effects on diverse nonhematopoietic organs and tissues. Although the precise mechanisms remain unclear, numerous studies in animal models of myocardial infarction (MI) and heart failure indicate that hematopoietic cytokines confer potent cardiovascular benefits, possibly through mobilization and subsequent homing of bone marrow-derived cells into the infarcted heart with consequent induction of myocardial repair involving multifarious mechanisms. In addition, these cytokines are also known to exert direct cytoprotective effects. However, results from small-scale clinical trials of G-CSF therapy as a single agent after acute MI have been discordant and largely disappointing. It is likely that cardiac repair following cytokine therapy depends on a number of known and unknown variables, and further experimental and clinical studies are certainly warranted to accurately determine the true therapeutic potential of such therapy. In this review, we discuss the biological features of several key hematopoietic cytokines and present the basic and clinical evidence pertaining to cardiac repair with hematopoietic cytokine therapy. PMID:21541807

  18. Cellular players of hematopoietic stem cell mobilization in the bone marrow niche.

    PubMed

    Tay, Joshua; Levesque, Jean-Pierre; Winkler, Ingrid G

    2017-02-01

    Hematopoietic stem cells (HSC) reside in perivascular regions of the bone marrow (BM) embedded within a complex regulatory unit called the niche. Cellular components of HSC niches include vascular endothelial cells, mesenchymal stromal progenitor cells and a variety of mature hematopoietic cells such as macrophages, neutrophils, and megakaryocytes-further regulated by sympathetic nerves and complement components as described in this review. Three decades ago the discovery that cytokines induce a large number of HSC to mobilize from the BM into the blood where they are easily harvested, revolutionised the field of HSC transplantation-curative for immune-deficiencies and some malignancies. However, despite now routine use of granulocyte-colony stimulating factor (G-CSF) to mobilise HSC for transplant, only in last 15 years has research on the mechanisms behind why and how HSC can be induced to move into the blood began. These studies have revealed the complexity of the niche that retains HSC in the BM. This review describes how BM niches and HSC themselves change during administration of G-CSF-or in the recovery phase of chemotherapy-to facilitate movement of HSC into the blood, and research now leading to development of novel therapeutics to further boost HSC mobilization and transplant success.

  19. Polar Residues in Transmembrane Helices can Decrease Electrophoretic Mobility in Polyacrylamide Gels Without Causing Helix Dimerization

    PubMed Central

    Walkenhorst, William F.; Merzlyakov, Mikhail; Hristova, Kalina; Wimley, William C.

    2010-01-01

    There are only a few available methods to study lateral interactions and self assembly of transmembrane helices. One of the most frequently used methods is sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) which can report on strong interactions between peptides in SDS solution. Here we offer a cautionary tale about studying the folding and assembly of membrane proteins using peptides and SDS-PAGE experiments as membrane mimetic systems. At least for the specific peptide and detergent systems studied here, we show that a polar asparagine residue in the 12th position of an otherwise hydrophobic helical segment of 20 amino acids causes a peptide to migrate on SDS-PAGE gels with an apparent molecular weight that is twice its true molecular weight, suggesting dimerization. However when examined carefully in SDS solutions and in situ in the polyacrylamide gel itself using Forster resonance energy transfer no interaction can be detected. Instead we show evidence suggesting that differential interactions between peptide and detergent drive the differences in electrophoretic mobility without any interaction between peptides. These results emphasize the need to apply multiple independent techniques to the study of membrane protein folding, and they highlight the usefulness of studying folding and structure of membrane proteins in lipid membranes rather than in detergents. PMID:19265670

  20. Bone fracture nonunion rate decreases with increasing age: A prospective inception cohort study.

    PubMed

    Zura, Robert; Braid-Forbes, Mary Jo; Jeray, Kyle; Mehta, Samir; Einhorn, Thomas A; Watson, J Tracy; Della Rocca, Gregory J; Forbes, Kevin; Steen, R Grant

    2017-02-01

    Fracture nonunion risk is related to severity of injury and type of treatment, yet fracture healing is not fully explained by these factors alone. We hypothesize that patient demographic factors assessable by the clinician at fracture presentation can predict nonunion. A prospective cohort study design was used to examine ~2.5 million Medicare patients nationwide. Patients making fracture claims in the 5% Medicare Standard Analytic Files in 2011 were analyzed; continuous enrollment for 12months after fracture was required to capture the ICD-9-CM nonunion diagnosis code (733.82) or any procedure codes for nonunion repair. A stepwise regression analysis was used which dropped variables from analysis if they did not contribute sufficient explanatory power. In-sample predictive accuracy was assessed using a receiver operating characteristic (ROC) curve approach, and an out-of-sample comparison was drawn from the 2012 Medicare 5% SAF files. Overall, 47,437 Medicare patients had 56,492 fractures and 2.5% of fractures were nonunion. Patients with healed fracture (age 75.0±12.7SD) were older (p<0.0001) than patients with nonunion (age 69.2±13.4SD). The death rate among all Medicare beneficiaries was 4.8% per year, but fracture patients had an age- and sex-adjusted death rate of 11.0% (p<0.0001). Patients with fracture in 14 of 18 bones were significantly more likely to die within one year of fracture (p<0.0001). Stepwise regression yielded a predictive nonunion model with 26 significant explanatory variables (all, p≤0.003). Strength of this model was assessed using an area under the curve (AUC) calculation, and out-of-sample AUC=0.710. A logistic model predicted nonunion with reasonable accuracy (AUC=0.725). Within the Medicare population, nonunion patients were younger than patients who healed normally. Fracture was associated with increased risk of death within 1year of fracture (p<0.0001) in 14 different bones, confirming that geriatric fracture is a major public

  1. Relationship between Decrease in Serum Sodium Level and Bone Mineral Density in Osteoporotic Fracture Patients.

    PubMed

    Kwak, Mi Kyung; Choi, Dughyun; Lee, Jae Hyuk; Kim, Hye Jeong; Park, Hyeong Kyu; Suh, Kyo Il; Yoo, Myung Hi; Byun, Dong Won

    2015-02-01

    Recently, it has been suggested that decrease in serum sodium level is associated with osteoporosis. However, no study in Korea has reported the association of decrease in serum sodium level with osteoporosis. In this study, we investigated the relationship between the decrease in serum sodium level and severity of osteoporotic fracture in patients. We enrolled 290 subjects who were admitted and operated at Soonchunhyang University Hospital due to major fractures. For the control group, we enrolled 1,027 subjects who visited a health promotion center. We carried a 1:1 matching with age and sex from the case group. In a total of 164 age- and sex-matched subjects, serum sodium level was significantly lower in the fracture group than in the non-fracture group (P=0.001). Serum sodium level was significantly lower in the severe osteoporosis group than that in the non-severe osteoporosis group (P=0.002). Old age and decrease in serum sodium level were independent risk factors of osteoporosis (odds ratio [OR]=1.088, P=0.008, confidence interval [CI]=[1.022-1.157]; OR= 0.840, P=0.037, CI=0.713-0.989). Serum sodium level was significantly lower in the fracture group than that in the non-fracture group and in the severe osteoporosis group than that in the non-severe osteoporosis group. Based on our results, the decrease in serum sodium level could be an independent risk factor for osteoporosis.

  2. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones.

    PubMed

    Shah, Krupa; Armamento-Villareal, Reina; Parimi, Nehu; Chode, Suresh; Sinacore, David R; Hilton, Tiffany N; Napoli, Nicola; Qualls, Clifford; Villareal, Dennis T

    2011-12-01

    Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight loss therapy should include an intervention such as exercise training (ET) to minimize bone loss. The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 years) obese (body mass index [BMI] ≥ 30  kg/m(2) ) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (-9.6%) and diet-exercise (-9.4%) groups, not in the exercise (-1%) and control (-0.2%) groups (between-group p  <  0.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (-1.1%) than in the diet group (-2.6%), whereas BMD increased in the exercise group (1.5%) (between-group p  <  0.001). Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%, respectively), whereas they decreased in the exercise group (-13% and -15%, respectively) (between-group p  <  0.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (-15%) compared with the diet group (9%) (p  =  0.04). Serum leptin and estradiol concentrations decreased in the diet (-25% and -15%, respectively) and diet-exercise (-38% and -13%, respectively) groups, not in the exercise and control groups (between-group p  =  0.001). Multivariate analyses revealed that changes in lean body mass (β  =  0.33), serum osteocalcin (β  = -0.24), and one-repetition maximum (1-RM) strength (β  =  0.23) were independent predictors of changes in hip BMD (all p  <

  3. Sodium-bicarbonated mineral water decreases aldosterone levels without affecting urinary excretion of bone minerals.

    PubMed

    Schoppen, Stefanie; Pérez-Granados, Ana M; Carbajal, Angeles; Sarriá, Beatriz; Navas-Carretero, Santiago; Pilar Vaquero, M

    2008-06-01

    AIM To assess in healthy postmenopausal women the influence of consuming sodium-bicarbonated mineral water on postprandial evolution of serum aldosterone and urinary electrolyte excretion. Eighteen postmenopausal women consumed 500 ml of two sodium-bicarbonated mineral waters (sodium-bicarbonated mineral water 1 and sodium-bicarbonated mineral water 2) and a low-mineral water with a standard meal. Postprandial blood samples were taken at 60, 120, 240, 360 and 420 min and aldosterone concentrations were measured. Postprandial urinary minerals were determined. Urinary and total mineral excretion and urinary mineral concentrations did not differ except for sodium concentration, which was significantly higher with sodium-bicarbonated mineral water 1 than with low-mineral water (P = 0.005). There was a time effect (P = 0.003) on the aldosterone concentration. At 120 min, aldosterone concentrations were lower with sodium-bicarbonated mineral water 1 (P = 0.021) and sodium-bicarbonated mineral water 2 (P = 0.030) compared with low-mineral water. Drinking a sodium-rich bicarbonated mineral water with a meal increases urinary sodium concentration excretion without changes in the excretion of potassium and bone minerals.

  4. Clinical Implications of Sarcopenia on Decreased Bone Density in Men With COPD.

    PubMed

    Hwang, Ji An; Kim, Young Sam; Leem, Ah Young; Park, Moo Suk; Kim, Se Kyu; Chang, Joon; Jung, Ji Ye

    2017-05-01

    Sarcopenia and osteoporosis are systemic features of COPD. The present study investigated the association between sarcopenia and osteopenia/osteoporosis and the factors associated with low bone mineral density (BMD) in men with COPD. Data from 777 men with COPD who underwent both pulmonary function test and dual-energy x-ray absorptiometry were extracted from the Korean National Health and Nutritional Examination Survey database between 2008 and 2011. Sarcopenia was assessed with the appendicular skeletal mass index (ASMI) and osteopenia/osteoporosis with the T-score. As the severity of airflow limitation increased, the prevalence of sarcopenia increased (Ptrend < .001). Additionally, as the degree of sarcopenia became severe, the prevalence of osteopenia/osteoporosis increased (Ptrend < .001), and a significant positive correlation was noted between appendicular skeletal muscle mass and BMD (ASMI/T-score: r = 0.408; P < .001). Sarcopenia was independently associated with an increased risk of low BMD in men with COPD (OR, 2.31; 95% CI, 1.53-3.46; P < .001). Old age and low fat mass were significantly associated with low BMD in both sarcopenic and non-sarcopenic participants. High serum hemoglobin and insulin levels were associated with a reduced risk of low BMD only in the sarcopenic participants, whereas exercise and dietary intake were associated with a reduced risk only in the non-sarcopenic participants. Sarcopenia is closely correlated with osteopenia/osteoporosis in men with COPD. Moreover, different factors are associated with low BMD according to the presence/absence of sarcopenia in that population. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  5. Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1.

    PubMed

    Huang, S; Kaw, M; Harris, M T; Ebraheim, N; McInerney, M F; Najjar, S M; Lecka-Czernik, B

    2010-04-01

    Type 2 diabetes is associated with normal-to-higher bone mineral density (BMD) and increased rate of fracture. Hyperinsulinemia and hyperglycemia may affect bone mass and quality in the diabetic skeleton. In order to dissect the effect of hyperinsulinemia from the hyperglycemic impact on bone homeostasis, we have analyzed L-SACC1 mice, a murine model of impaired insulin clearance in liver causing hyperinsulinemia and insulin resistance without fasting hyperglycemia. Adult L-SACC1 mice exhibit significantly higher trabecular and cortical bone mass, attenuated bone formation as measured by dynamic histomorphometry, and reduced number of osteoclasts. Serum levels of bone formation (BALP) and bone resorption markers (TRAP5b and CTX) are decreased by approximately 50%. The L-SACC1 mutation in the liver affects myeloid cell lineage allocation in the bone marrow: the (CD3(-)CD11b(-)CD45R(-)) population of osteoclast progenitors is decreased by 40% and the number of (CD3(-)CD11b(-)CD45R(+)) B-cell progenitors is increased by 60%. L-SACC1 osteoclasts express lower levels of c-fos and RANK and their differentiation is impaired. In vitro analysis corroborated a negative effect of insulin on osteoclast recruitment, maturation and the expression levels of c-fos and RANK transcripts. Although bone formation is decreased in L-SACC1 mice, the differentiation potential and expression of the osteoblast-specific gene markers in L-SACC1-derived mesenchymal stem cells (MSC) remain unchanged as compared to the WT. Interestingly, however, MSC from L-SACC1 mice exhibit increased PPARgamma2 and decreased IGF-1 transcript levels. These data suggest that high bone mass in L-SACC1 animals results, at least in part, from a negative regulatory effect of insulin on bone resorption and formation, which leads to decreased bone turnover. Because low bone turnover contributes to decreased bone quality and an increased incidence of fractures, studies on L-SACC1 mice may advance our understanding of

  6. Deletion of Cx43 from osteocytes results in defective bone material properties but does not decrease extrinsic strength in cortical bone.

    PubMed

    Bivi, Nicoletta; Nelson, Mark T; Faillace, Meghan E; Li, Jiliang; Miller, Lisa M; Plotkin, Lilian I

    2012-09-01

    Deletion of connexin (Cx) 43 from osteoblasts and osteocytes (OCN-Cre;Cx43(fl/-) mice) or from osteocytes only (DMP1-8kb-Cre;Cx43(fl/fl) mice) results in increased cortical, but not cancellous, osteocyte apoptosis and widening of the femoral midshaft without changes in cortical thickness. Despite the consequent larger moment of inertia, stiffness and ultimate load, measures of mechanical strength assessed by three-point bending, are not higher in either model of Cx43 deficiency due to reduced Young's modulus, a measure of the stiffness of the material per unit of area. In OCN-Cre;Cx43(fl/-) mice, this was accompanied by a reduced ratio of nonreducible/reducible collagen cross-links as assessed by Fourier transformed infrared imaging (FTIRI) in the femoral diaphysis. On the other hand, DMP1-8kb-Cre;Cx43(fl/fl) mice did not show a significant reduction in collagen maturation in the same skeletal site, but a small decrease in mineralization was detected by FTIRI. Remarkably, both osteoblastic and osteocytic cells lacking Cx43 expressed lower mRNA levels of lysyl oxidase, a crucial enzyme involved in collagen maturation. These findings suggest that Cx43 expression in osteoblasts is involved in maintaining the quality of the bone matrix in cortical bone through the maturation of collagen cross-links. Osteocytic Cx43 expression is important also to maintain the stiffness of the bone material, where Cx43 deficiency results in local reduction in mineralization, possibly due to osteocyte apoptosis.

  7. A test of bone mobilization relative to reproductive demand: skeletal quality is improved in cannibalistic females with large litters.

    PubMed

    Hood, Wendy R

    2012-01-01

    In species with repeated bouts of reproduction, a female's ability to retain sufficient tissue for self-maintenance is essential to her survival and capacity for future reproduction. Loss of bone mineral content results in bone fragility and the possibility of reduced survival, so females should guard against the overuse of their bone mineral during reproduction. Given these constraints, I predicted that bone mobilization would increase with litter size in mice but plateau before maximum litter size was reached. To test this idea, I manipulated the litter sizes of house mice on the day of parturition to 3, 8, 13, and 18 offspring. At weaning, I euthanized the females and calculated whole-body and bone mineral composition. The total mineral content of females' femurs dropped as litter size increased to the average litter size for this strain of mouse (13) but surprisingly, femoral mineral content was higher for females assigned the largest litter sizes (18). Seven of the nine females assigned 18 young cannibalized some of their offspring. For females assigned to these larger litters, femoral ash content was not correlated with number of young consumed, suggesting that mineral recycling had little effect on final bone mineral content. However, nursing effort (accounting for young lost to cannibalism) was correlated with maternal femoral ash at weaning. These finding suggest that the high bone mineral content of females assigned the largest litters was associated with a reduction in endogenous mineral allocated to the litter.

  8. The mobilization and effect of endogenous bone marrow progenitor cells in diabetic wound healing.

    PubMed

    Fiorina, Paolo; Pietramaggiori, Giorgio; Scherer, Saja S; Jurewicz, Mollie; Mathews, Jasmine C; Vergani, Andrea; Thomas, Gebhard; Orsenigo, Elena; Staudacher, Carlo; La Rosa, Stefano; Capella, Carlo; Carothers, Adelaide; Zerwes, Hans-Gunter; Luzi, Livio; Abdi, Reza; Orgill, Dennis P

    2010-01-01

    Diabetic patients suffer from impaired wound healing, characterized by only modest angiogenesis and cell proliferation. Stem cells may stimulate healing, but little is known about the kinetics of mobilization and function of bone marrow progenitor cells (BM-PCs) during diabetic wound repair. The objective of this study was to investigate the kinetics of BM-PC mobilization and their role during early diabetic wound repair in diabetic db/db mice. After wounding, circulating hematopoietic stem cells (Lin(-)c-Kit(+)Sca-1(+)) stably increased in the periphery and lymphoid tissue of db/db mice compared to unwounded controls. Peripheral endothelial progenitor cells (CD34(+)VEGFR(+)) were 2.5- and 3.5-fold increased on days 6 and 10 after wounding, respectively. Targeting the CXCR4-CXCL12 axis induced an increased release and engraftment of endogenous BM-PCs that was paralleled by an increased expression of CXCL12/SDF-1α in the wounds. Increased levels of peripheral and engrafted BM-PCs corresponded to stimulated angiogenesis and cell proliferation, while the addition of an agonist (GM-CSF) or an antagonist (ACK2) did not further modulate wound healing. Macroscopic histological correlations showed that increased levels of stem cells corresponded to higher levels of wound reepithelialization. After wounding, a natural release of endogenous BM-PCs was shown in diabetic mice, but only low levels of these cells homed in the healing tissue. Higher levels of CXCL12/SDF-1α and circulating stem cells were required to enhance their engraftment and biological effects. Despite controversial data about the functional impairment of diabetic BM-PCs, in this model our data showed a residual capacity of these cells to trigger angiogenesis and cell proliferation.

  9. Acute mobilization and migration of bone marrow-derived stem cells following anterior cruciate ligament rupture.

    PubMed

    Maerz, T; Fleischer, M; Newton, M D; Davidson, A; Salisbury, M; Altman, P; Kurdziel, M D; Anderson, K; Bedi, A; Baker, K C

    2017-08-01

    Little is known regarding acute local and systemic processes following anterior cruciate ligament (ACL) rupture. No study has elucidated whether bone marrow-derived mesenchymal stem cells (MSCs) are mobilized into circulation and recruited to the injured joint. In Part 1, Lewis rats were randomized to noninvasive ACL rupture (Rupture) or non-injured (Control) (n = 6/group). After 72 h, whole blood MSC concentration was assessed using flow cytometry. Synovial fluid and serum were assayed for stromal cell-derived factor (SDF)-1α and cartilage degeneration biomarkers, respectively. In Part 2, 12 additional rats were randomized and intravenously-injected with fluorescently-labeled allogenic MSCs. Cell tracking was performed using longitudinal, in vivo and ex vivo near-infrared (NIR) imaging and histology. Synovium SDF-1α and interleukin (IL)-17A immunostaining was performed. Serum was assayed for SDF-1α and 29 other cytokines. In Part 1, there was a significant increase in MSC concentration and synovial fluid SDF-1α in Rupture. No differences in cartilage biomarkers were observed. In Part 2, Rupture had significantly higher NIR signal at 24, 48, and 72 h, indicating active recruitment of MSCs to the injured joint. Ex vivo cell tracking demonstrated MSC localization in the synovium and myotendinous junction (MTJ) of the quadriceps. Injured synovia exhibited increased synovitis grade and higher degree of IL-17A and SDF-1α immunostaining. ACL rupture induced peripheral blood mobilization of MSCs and migration of intravenously-injected allogenic MSCs to the injured joint, where they localized in the synovium and quadriceps MTJ. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Bone marrow-derived HL mitigates bone marrow-derived CETP-mediated decreases in HDL in mice globally deficient in HL and the LDLr.

    PubMed

    Hime, Neil J; Black, Audrey S; Bonnet, David J; Curtiss, Linda K

    2014-09-01

    The objective of this study was to determine the combined effects of HL and cholesteryl ester transfer protein (CETP), derived exclusively from bone marrow (BM), on plasma lipids and atherosclerosis in high-fat-fed, atherosclerosis-prone mice. We transferred BM expressing these proteins into male and female double-knockout HL-deficient, LDL receptor-deficient mice (HL(-/-)LDLr(-/-)). Four BM chimeras were generated, where BM-derived cells expressed 1) HL but not CETP, 2) CETP and HL, 3) CETP but not HL, or 4) neither CETP nor HL. After high-fat feeding, plasma HDL-cholesterol (HDL-C) was decreased in mice with BM expressing CETP but not HL (17 ± 4 and 19 ± 3 mg/dl, female and male mice, respectively) compared with mice with BM expressing neither CETP nor HL (87 ± 3 and 95 ± 4 mg/dl, female and male mice, respectively, P < 0.001 for both sexes). In female mice, the presence of BM-derived HL mitigated this CETP-mediated decrease in HDL-C. BM-derived CETP decreased the cholesterol component of HDL particles and increased plasma cholesterol. BM-derived HL mitigated these effects of CETP. Atherosclerosis was not significantly different between BM chimeras. These results suggest that BM-derived HL mitigates the HDL-lowering, HDL-modulating, and cholesterol-raising effects of BM-derived CETP and warrant further studies to characterize the functional properties of these protein interactions.

  11. Using Mobile Technology in an Urban High School to Decrease Adult Prompting during in School Transitions for Students Identified with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Christman, Jennifer T.

    2013-01-01

    The aim of this study was to examine the application of video modeling on mobile technology to increase efficiency in the classroom for students identified with intellectual disabilities. Specially, this study sought to identify if video modeling on mobile technology could decrease adult prompting for students with intellectual disabilities during…

  12. Using Mobile Technology in an Urban High School to Decrease Adult Prompting during in School Transitions for Students Identified with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Christman, Jennifer T.

    2013-01-01

    The aim of this study was to examine the application of video modeling on mobile technology to increase efficiency in the classroom for students identified with intellectual disabilities. Specially, this study sought to identify if video modeling on mobile technology could decrease adult prompting for students with intellectual disabilities during…

  13. T helper 17 and T helper 1 cells are increased but regulatory T cells are decreased in subchondral bone marrow microenvironment of patients with rheumatoid arthritis

    PubMed Central

    Wang, Ting; Li, Shufeng; Yang, Yun; Zhang, Kaining; Dong, Shixiao; Wang, Xiuhua; Liu, Xinguang; Ren, Yanjun; Zhang, Ming; Yan, Xinfeng; Li, Jianmin; Zhang, Lei

    2016-01-01

    Objectives: The present study is to investigate the profiles of Th17, Th1 and Treg cells in bone marrow of patients with rheumatoid arthritis (RA). Methods: Flow cytometry was used to analyze the frequencies of Th17, Th1 and Treg cells in paired peripheral blood and bone marrow of 26 RA patients and 11 osteoarthritis (OA) patients, as well as 10 healthy controls. In addition, the disease activity was analyzed by the 28-joint disease activity score (DAS28). Results: The frequencies of Th17 and Th1 cells were significantly elevated in bone marrow of RA patients. Importantly, Th17 and Th1 cells were significantly elevated in bone marrow compared with the matched peripheral blood from RA patients. However, Treg cells were significantly decreased in bone marrow of RA patients compared with the matched peripheral blood of RA patients and bone marrow of osteoarthritis patients and healthy controls. Moreover, the frequencies of tumor necrosis factor-α-producing T cells were significantly elevated in bone marrow from RA patients. Additionally, Th17 and Th1 cells in bone marrow were positively correlated with DAS28, while Treg cells were negatively correlated with DAS28. Conclusions: The present study demonstrates that Th17 and Th1 cells are markedly increased in bone marrow from RA patients. By contrast, Treg cells are significantly decreased in bone marrow from RA patients. These results suggest that local abnormality of Th17, Th1 and Treg cells in bone marrow of RA patients may contribute to bone destruction in skeletal system. PMID:27508016

  14. Diabetes causes bone marrow autonomic neuropathy and impairs stem cell mobilization via dysregulated p66Shc and Sirt1.

    PubMed

    Albiero, Mattia; Poncina, Nicol; Tjwa, Marc; Ciciliot, Stefano; Menegazzo, Lisa; Ceolotto, Giulio; Vigili de Kreutzenberg, Saula; Moura, Rute; Giorgio, Marco; Pelicci, Piergiuseppe; Avogaro, Angelo; Fadini, Gian Paolo

    2014-04-01

    Diabetes compromises the bone marrow (BM) microenvironment and reduces the number of circulating CD34(+) cells. Diabetic autonomic neuropathy (DAN) may impact the BM, because the sympathetic nervous system is prominently involved in BM stem cell trafficking. We hypothesize that neuropathy of the BM affects stem cell mobilization and vascular recovery after ischemia in patients with diabetes. We report that, in patients, cardiovascular DAN was associated with fewer circulating CD34(+) cells. Experimental diabetes (streptozotocin-induced and ob/ob mice) or chemical sympathectomy in mice resulted in BM autonomic neuropathy, impaired Lin(-)cKit(+)Sca1(+) (LKS) cell and endothelial progenitor cell (EPC; CD34(+)Flk1(+)) mobilization, and vascular recovery after ischemia. DAN increased the expression of the 66-kDa protein from the src homology and collagen homology domain (p66Shc) and reduced the expression of sirtuin 1 (Sirt1) in mice and humans. p66Shc knockout (KO) in diabetic mice prevented DAN in the BM, and rescued defective LKS cell and EPC mobilization. Hematopoietic Sirt1 KO mimicked the diabetic mobilization defect, whereas hematopoietic Sirt1 overexpression in diabetes rescued defective mobilization and vascular repair. Through p66Shc and Sirt1, diabetes and sympathectomy elevated the expression of various adhesion molecules, including CD62L. CD62L KO partially rescued the defective stem/progenitor cell mobilization. In conclusion, autonomic neuropathy in the BM impairs stem cell mobilization in diabetes with dysregulation of the life-span regulators p66Shc and Sirt1.

  15. Bone marrow stem/progenitor cell mobilization in C57BL/6J and BALB/c mice.

    PubMed

    Lee, Hakmo; Che, Jeong-Hwan; Oh, Ju Eun; Chung, Sung Soo; Jung, Hye Seung; Park, Kyong Soo

    2014-03-01

    Bone marrow (BM) has been considered as a reservoir of stem/progenitor cells which are able to differentiate into ectodermal, endodermal, and mesodermal origins in vitro as well as in vivo. Following adequate stimulation, such as granulocyte stimulating factor (G-CSF) or AMD3100, BM resident stem/progenitor cells (BMSPCs) can be mobilized to peripheral blood. Several host-related factors are known to participate in this mobilization process. In fact, a significant number of donors are resistant to G-CSF induced mobilization protocols. AMD3100 is currently used in combination with G-CSF. However, information regarding host-related factors which may influence the AMD3100 directed mobilization is extremely limited. In this study, we were to get some more knowledge on the host-related factors that affect the efficiency of AMD3100 induced mobilization by employing in vivo mobilization experiments. As a result, we found that C57BL/6J mice are more sensitive to AMD3100 but less sensitive to G-CSF which promotes the proliferation of BMSPCs. We excluded S1P as one of the host related factor which influences AMD3100 directed mobilization because pre-treatment of S1P receptor antagonist FTY720 did not inhibit BMSPC mobilization. Further in vitro experiments revealed that BALB/c mice, compared to C57BL/6J mice, have less BMSPCs which migrate in response to host related factors such as sphingosine-1-phosphate (S1P) and to CXCL12. We conclude that AMD3100-directed mobilization depends on the number of BMSPCs rather than on the host-related factors. These results suggest that the combination of AMD3100 and G-CSF is co-operative and is optimal for the mobilization of BMSPCs.

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

    PubMed Central

    Ye, Chenyi; Xu, Mingyuan; Wang, Shengdong; Jiang, Shuai; Chen, Xi; Zhou, Xiaoyu; He, Rongxin

    2016-01-01

    Background There is conflicting evidence regarding the association between decreased bone mineral density (BMD) and atherosclerosis. To this end, we performed a systematic review and meta-analysis to clarify the association. Methods To identify relevant studies, PubMed, Embase, and the Cochrane Library were systematically searched up to November 2015. All observational and comparative studies directly investigating the relationship between decreased BMD and clinical consequences of atherosclerotic vascular abnormalities, including carotid artery calcification (CAC), cardiovascular disease (CAD), and coronary artery disease (CAD) were obtained, without limitation of language or publication year. Results A total of 25 studies involving 10,299 patients were included. The incidence of atherosclerotic vascular abnormalities was significantly increased in low BMD patients, compared to patients with normal BMD (OR, 1.81, 95% CI [1.01, 2.19], p<0.00001)). Similar results were also observed for postmenopausal women (OR, 2.23, 95% CI [1.72, 2.89], p<0.00001). Subgroup analyses of osteopenia, osteoporosis, and normal BMD also revealed that the combined ORs for the incidence of atherosclerotic vascular abnormalities increased as BMD decreased. Of note, after adjusting for age, sex, body mass index (BMI) and other vascular risk factors, decreased BMD remained significantly associated with the incidence of atherosclerotic vascular abnormalities (OR, 2.96, 95% CI [2.25, 3.88], p < 0.00001). Conclusions Based on the results of this study, decreased BMD is an independent predictor for the development of atherosclerosis in elderly individuals. Moreover, the risk of atherosclerotic vascular abnormalities increased as BMD decreased. Future studies focusing on individuals with different severities of atherosclerosis and comorbidities are of interest. PMID:27149062

  17. Bone mesenchymal stem cell-conditioned medium decreases the generation of astrocytes during the process of neural stem cells differentiation.

    PubMed

    Fang, Huang; Song, Peiwen; Shen, Yuening; Shen, Cailiang; Liu, Xiaoying

    2017-06-26

    The aim of this study was to investigate the effect of bone mesenchymal stem cell (BMSC) conditioned medium (CM) and Bone morphogenetic protein-4 (BMP-4) on the generation of astrocytes during the process of NSCs differentiation. Neural stem cells (NSCs) were grown under different culture conditions. The First Affiliated Hospital of Anhui Medical University, Hefei, China. The study consisted of four groups: NSCs cultured under control conditions (group 1) or with the addition of BMSC-CM (group 2);(BMP-4) (group 3) or both (group 4).The expression of glial fibrillary acidic protein (GFAP) was detected by immunocytochemical staining and Western blotting. The expression of GFAP was higher in Group3 and lower in Group 2 compared to that in Group 1. The expression of GFAP in Group 4 was intermediate between that of Group 2 and Group 3. These results suggest that BMSC-CM can decrease the generation of astrocytes and that the inhibition of the (BMP-4) /Smad1/5/8 signaling pathway may be the underlying mechanism. This phenomenon may be mediated by increasing the expression of Smad6.

  18. Six months of disuse during hibernation does not increase intracortical porosity or decrease cortical bone geometry, strength, or mineralization in black bear (Ursus americanus) femurs.

    PubMed

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Bunnell, Kevin; Auger, Janene; Black, Hal L; Donahue, Seth W

    2009-07-22

    Disuse typically uncouples bone formation from resorption, leading to bone loss which compromises bone mechanical properties and increases the risk of bone fracture. Previous studies suggest that bears can prevent bone loss during long periods of disuse (hibernation), but small sample sizes have limited the conclusions that can be drawn regarding the effects of hibernation on bone structure and strength in bears. Here we quantified the effects of hibernation on structural, mineral, and mechanical properties of black bear (Ursus americanus) cortical bone by studying femurs from large groups of male and female bears (with wide age ranges) killed during pre-hibernation (fall) and post-hibernation (spring) periods. Bone properties that are affected by body mass (e.g. bone geometrical properties) tended to be larger in male compared to female bears. There were no differences (p>0.226) in bone structure, mineral content, or mechanical properties between fall and spring bears. Bone geometrical properties differed by less than 5% and bone mechanical properties differed by less than 10% between fall and spring bears. Porosity (fall: 5.5+/-2.2%; spring: 4.8+/-1.6%) and ash fraction (fall: 0.694+/-0.011; spring: 0.696+/-0.010) also showed no change (p>0.304) between seasons. Statistical power was high (>72%) for these analyses. Furthermore, bone geometrical properties and ash fraction (a measure of mineral content) increased with age and porosity decreased with age. These results support the idea that bears possess a biological mechanism to prevent disuse and age-related osteoporoses.

  19. High-fat Diet Decreases Cancellous Bone Mass But Has No Effect on Cortical Bone Mass in the Tibia in Mice

    USDA-ARS?s Scientific Manuscript database

    Introduction: Body mass has a positive effect on bone mineral density and the strength. Whether mass derived from an obesity condition is beneficial to bone has not been established; neither have the mechanism by which obesity affects bone metabolism. The aim of this study was to examine the effects...

  20. Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth.

    PubMed

    Kung, Louise H W; Rajpar, M Helen; Preziosi, Richard; Briggs, Michael D; Boot-Handford, Raymond P

    2015-01-01

    Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog) in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.

  1. Do all β-blockers attenuate the excess hematopoietic progenitor cell mobilization from the bone marrow following trauma/hemorrhagic shock?

    PubMed

    Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C; Alzate, Walter D; Livingston, David H; Mohr, Alicia M

    2014-04-01

    Severe injury results in increased mobilization of hematopoietic progenitor cells (HPC) from the bone marrow (BM) to sites of injury, which may contribute to persistent BM dysfunction after trauma. Norepinephrine is a known inducer of HPC mobilization, and nonselective β-blockade with propranolol has been shown to decrease mobilization after trauma and hemorrhagic shock (HS). This study will determine the role of selective β-adrenergic receptor blockade in HPC mobilization in a combined model of lung contusion (LC) and HS. Male Sprague-Dawley rats were subjected to LC, followed by 45 minutes of HS. Animals were then randomized to receive atenolol (LCHS + β1B), butoxamine (LCHS + β2B), or SR59230A (LCHS + β3B) immediately after resuscitation and daily for 6 days. Control groups were composed of naive animals. BM cellularity, %HPCs in peripheral blood, and plasma granulocyte-colony stimulating factor levels were assessed at 3 hours and 7 days. Systemic plasma-mediated effects were evaluated in vitro by assessment of BM HPC growth. Injured lung tissue was graded histologically by a blinded reader. The use of β2B or β3B following LCHS restored BM cellularity and significantly decreased HPC mobilization. In contrast, β1B had no effect on HPC mobilization. Only β3B significantly reduced plasma G-CSF levels. When evaluating the plasma systemic effects, both β2B and β3B significantly improved BM HPC growth as compared with LCHS alone. The use of β2 and β3 blockade did not affect lung injury scores. Both β2 and β3 blockade can prevent excess HPC mobilization and BM dysfunction when given after trauma and HS, and the effects seem to be mediated systemically, without adverse effects on subsequent healing. Only treatment with β3 blockade reduced plasma G-CSF levels, suggesting different mechanisms for adrenergic-induced G-CSF release and mobilization of HPCs. This study adds to the evidence that therapeutic strategies that reduce the exaggerated sympathetic

  2. Bone Morphogenetic Protein Type I Receptor Antagonists Decrease Growth and Induce Cell Death of Lung Cancer Cell Lines

    PubMed Central

    Langenfeld, Elaine; Hong, Charles C.; Lanke, Gandhi; Langenfeld, John

    2013-01-01

    Bone morphogenetic proteins (BMPs) are highly conserved morphogens that are essential for normal development. BMP-2 is highly expressed in the majority of non-small cell lung carcinomas (NSCLC) but not in normal lung tissue or benign lung tumors. The effects of the BMP signaling cascade on the growth and survival of cancer cells is poorly understood. We show that BMP signaling is basally active in lung cancer cell lines, which can be effectively inhibited with selective antagonists of the BMP type I receptors. Lung cancer cell lines express alk2, alk3, and alk6 and inhibition of a single BMP receptor was not sufficient to decrease signaling. Inhibition of more than one type I receptor was required to decrease BMP signaling in lung cancer cell lines. BMP receptor antagonists and silencing of BMP type I receptors with siRNA induced cell death, inhibited cell growth, and caused a significant decrease in the expression of inhibitor of differentiation (Id1, Id2, and Id3) family members, which are known to regulate cell growth and survival in many types of cancers. BMP receptor antagonists also decreased clonogenic cell growth. Knockdown of Id3 significantly decreased cell growth and induced cell death of lung cancer cells. H1299 cells stably overexpressing Id3 were resistant to growth suppression and induction of cell death induced by the BMP antagonist DMH2. These studies suggest that BMP signaling promotes cell growth and survival of lung cancer cells, which is mediated through its regulation of Id family members. Selective antagonists of the BMP type I receptors represents a potential means to pharmacologically treat NSCLC and other carcinomas with an activated BMP signaling cascade. PMID:23593444

  3. Comparison of PACS and Bone Ninja mobile application for assessment of lower extremity limb length discrepancy and alignment.

    PubMed

    Whitaker, Amanda T; Gesheff, Martin G; Jauregui, Julio J; Herzenberg, John E

    2016-10-01

    There are over 500 medically related applications (apps) for mobile devices. Very few of these applications undergo testing and peer-review for accuracy. The purpose of this study is to assess the accuracy of limb deformity measurements on the Bone Ninja app compared to PACS and to determine the intra- and inter-observer variability among different orthopaedic practitioners. Four participants (attending, senior and junior resident, and physician assistant) measured the leg length (LL), the lateral distal femoral angle (LDFA), and the medial proximal tibial angle (MPTA) of 48 limbs (24 patients), twice with both Bone Ninja and PACS. The difference between the measurements obtained with the Bone Ninja app and PACS were measured. We determined the consistency of the intra-observer intra-class correlation coefficient (ICC) for both systems. There were no statistical differences in leg length discrepancy (LLD), MPTA, or LDFA measurements between Bone Ninja and PACS (p = 0.96, 0.87, and 0.97, respectively). The intra-observer ICC for the LL, LDFA, and MPTA was similar between Bone Ninja and PACS (0.83, 0.89, and 0.96 vs. 0.96, 0.93, and 0.95, respectively). The inter-observer ICC was similar between Bone Ninja and PACS (0.95, 0.96, and 0.99 vs. 0.99, 0.98, and 0.98, respectively). This study demonstrates that Bone Ninja is an accurate educational tool for measuring LLD, LDFA, and MPTA. Both systems are reliable instruments for evaluating limb length differences and angles on standing radiographs for pre-operative deformity planning and education. This is the first study to evaluate the accuracy of Bone Ninja compared to the gold standard of PACS.

  4. Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts.

    PubMed

    Caillot-Augusseau, A; Vico, L; Heer, M; Voroviev, D; Souberbielle, J C; Zitterman, A; Alexandre, C; Lafage-Proust, M H

    2000-08-01

    Microgravity induces bone loss by mechanism(s) that remain largely unknown. We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

  5. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

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

  6. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta

    PubMed Central

    Panaroni, Cristina; Gioia, Roberta; Lupi, Anna; Besio, Roberta; Goldstein, Steven A.; Kreider, Jaclynn; Leikin, Sergey; Vera, Juan Carlos; Mertz, Edward L.; Perilli, Egon; Baruffaldi, Fabio; Villa, Isabella; Farina, Aurora; Casasco, Marco; Cetta, Giuseppe; Rossi, Antonio; Frattini, Annalisa; Marini, Joan C.; Vezzoni, Paolo

    2009-01-01

    Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (IUT) may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knockin mouse with a classical glycine substitution in type I collagen [α1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic tissues differentiated to trabecular and cortical bone cells and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (P < .05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting IUT as a promising approach for the treatment of genetic bone diseases. PMID:19414862

  7. Decreased peak bone mass is associated with a 3-bp deletion/insertion of the CYP19 intron 4 polymorphism: preliminary data from the GOOS study.

    PubMed

    Kastelan, D; Grubic, Z; Kraljevic, I; Duric, K; Kardum, I; Dusek, T; Stingl, K; Giljevic, Z; Kerhin-Brkljacic, V; Suchanek, E; Korsic, M

    2007-06-01

    Finding that estrogen plays an important role in bone homeostasis in men prompted research on relationship of polymorphism at the CYP19 gene and the bone mass. Therefore, influence of 3-bp deletion/insertion polymorphism of CYP19 (TTTA)7 allele on the peak bone mass attainment in males was studied. Fifty-eight unrelated male participants, aged 21-35, were selected depending on the presence of (TTTA)7 (no.=19) or (TTTA)7-3 (no.=39) alleles from the initial cohort of 92 young males. Heterozygotes (TTTA)7/(TTTA)7-3 (no.=13) were not included in the analysis. Serum levels of estradiol, free testosterone, 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, and beta-crosslaps were measured. Bone mass was measured by DXA at the hip and at the spine. (TTTA)7-3 allele was associated with significantly lower femoral neck bone mineral density (BMD) (p=0.02). Logistic regression model indicated strong association of (TTTA)7-3 allele with low BMD in the range of osteopenia/osteoporosis (p=0.014, odds ratio 12.36, confidence intervals 1.65-92.46). In the present study association of 3-bp deletion polymorphism of the (TTTA)7 allele with decreased peak bone mass in males is reported for the first time. However, further studies are necessary to elucidate the functional relevance of this polymorphism.

  8. Larger femoral periprosthetic bone mineral density decrease following total hip arthroplasty for femoral neck fracture than for osteoarthritis: a prospective, observational cohort study.

    PubMed

    Mann, Tobias; Eisler, Thomas; Bodén, Henrik; Muren, Olle; Stark, André; Salemyr, Mats; Sköldenberg, Olof

    2015-04-01

    Studies on patients with degenerative joint disease of the hip show that femoral periprosthetic bone mineral decreases following total hip arthroplasty. Scarcely any osteodensitometric data exist on femoral neck fracture (FNF) patients and periprosthetic bone remodelling. In two parallel cohorts we enrolled 87 patients (mean age, 72 ± 12 years; male:female ratio, 30:57) undergoing total hip arthroplasty for either primary osteoarthritis (OA) of the hip (n = 37) or for an acute FNF (n = 50) and followed them for a mean of 5.4 years. Outcomes were bone mineral density (BMD) changes in the periprosthetic Gruen zones 1-7, the incidence of periprosthetic fractures and clinical outcome. The bone mineral loss in the fracture group was more than twice that of the osteoarthritis group, -16.9% versus -6.8% (p = 0.004). The incidence of periprosthetic fractures was 12% (6/50) in the fracture cohort compared with none (0%) in the OA cohort (p = 0.03). Periprosthetic bone mineral loss following total hip arthroplasty is significantly greater in patients who are treated for acute FNF than in OA patients. This decrease of BMD follows a different pattern with the FNF patients losing larger proportions of bone in Gruen zones 1, 2, 6, and 7 while the OA patients tend to have larger losses only in zones 1 and 7. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Enhanced mobilization of the bone marrow–derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction

    PubMed Central

    Turan, R G; Bozdag-T, I; Turan, C H; Ortak, J; Akin, I; Kische, S; Schneider, H; Rauchhaus, M; Rehders, T C; Kleinfeldt, T; Belu, C; Amen, S; Hermann, T; Yokus, S; Brehm, M; Steiner, S; Chatterjee, T; Sahin, K; Nienaber, C A; Ince, H

    2012-01-01

    Abstract Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow–derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45+- and CD133/45+-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45+: P < 0.001, CD133/45+: P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45+ and CD133/45+ BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM-CPCs in PB and this might increase the regenerative potency after AMI. PMID:21707914

  10. Involuntary wheel running improves but does not fully reverse the deterioration of bone structure of obese rats despite decreasing adiposity

    USDA-ARS?s Scientific Manuscript database

    Excessive adiposity induced by a high-fat diet is detrimental to bone structure and strength in various animal models. This study investigated whether exercise or anti-oxidant supplementation with vitamin C and E during exercise counteracts bone structure deterioration at different skeletal sites an...

  11. Mobility during the neolithic and bronze age in northern ireland explored using strontium isotope analysis of cremated human bone.

    PubMed

    Snoeck, Christophe; Pouncett, John; Ramsey, Greer; Meighan, Ian G; Mattielli, Nadine; Goderis, Steven; Lee-Thorp, Julia A; Schulting, Rick J

    2016-07-01

    As many individuals were cremated in Neolithic and Bronze Age Ireland, they have not featured in investigations of individual mobility using strontium isotope analysis. Here, we build on recent experiments demonstrating excellent preservation of biogenic (87) Sr/(86) Sr in calcined bone to explore mobility in prehistoric Northern Ireland. A novel method of strontium isotope analysis is applied to calcined bone alongside measurements on tooth enamel to human remains from five Neolithic and Bronze Age sites in Northern Ireland. We systematically sampled modern vegetation around each site to characterize biologically available strontium, and from this calculated expected values for humans consuming foods taken from within 1, 5, 10 and 20 Km catchments. This provides a more nuanced way of assessing human use of the landscape and mobility than the 'local' vs. 'non-local' dichotomy that is often employed. The results of this study 1) provide further support for the reliability of strontium isotope analysis on calcined bone, and 2) demonstrate that it is possible to identify isotopic differences between individuals buried at the same site, with some consuming food grown locally (within 1-5 Km) while others clearly consumed food from up to 50 Km away from their burial place. Hints of patterning emerge in spite of small sample numbers. At Ballynahatty, for instance, those represented by unburnt remains appear to have consumed food growing locally, while those represented by cremated remains did not. Furthermore, it appears that some individuals from Ballynahatty, Annaghmare and Clontygora either moved in the last few years of their life or their cremated remains were brought to the site. These results offer new insights into the choice behind coterminous cremation and inhumation rites in the Neolithic. Am J Phys Anthropol 160:397-413, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice

    PubMed Central

    Wang, Li-Li; Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Alaaeddine, Ghina; Li, Jimei; Wei, Ling; Yu, Shan Ping

    2014-01-01

    Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke. PMID:24503654

  13. The vitamin D analog ZK191784 normalizes decreased bone matrix mineralization in mice lacking the calcium channel TRPV5.

    PubMed

    van der Eerden, Bram C J; Fratzl-Zelman, Nadja; Nijenhuis, Tom; Roschger, Paul; Zügel, Ulrich; Steinmeyer, Andreas; Hoenderop, Joost G J; Bindels, René J M; Klaushofer, Klaus; van Leeuwen, Johannes P T M

    2013-02-01

    Mice lacking the renal epithelial Ca(2+) channel TRPV5 (TRPV5(-/-)) display impaired renal Ca(2+) reabsorption, hypercalciuria, and intestinal Ca(2+) hyperabsorption, due to secondary hypervitaminosis D. Using these mice, we previously demonstrated that ZK191784 acts as an intestine-specific 1,25(OH)(2) D(3) antagonist without affecting serum calcium levels. On the other hand, it acted as an agonist in the kidney and the effects of ZK191784 on bone were ambiguous. The present study was undertaken to further evaluate the effect of the vitamin D receptor antagonist on murine bone in mice lacking TRPV5. Eight-week-old female Trpv5(+/+) and Trpv5(-/-) mice were treated for 4 weeks with or without 50 µg/kg/day ZK191784. Quantitative backscattered electron imaging showed that the reduced bone matrix mineralization found in femoral bones of Trpv5(-/-) mice was partially but significantly restored upon ZK191784 treatment, just as we observed for trabecular bone thickness. This supports the significance of 1,25(OH)(2) D(3) and optimal control of Ca(2+) homeostasis for bone formation and matrix mineralization. Restoration also took place at the bone gene expression level, where 1α-hydroxylase (Cyp27b1) mRNA in femurs from ZK-treated Trpv5(-/-) mice was upregulated compared to control levels. The downregulated 24-hydroxylase (Cyp24a1) gene expression in femoral bone indicated local vitamin D resistance in the mice treated with ZK191784. Phosphate homeostasis was unaffected between the groups as shown by unaltered serum PO(4)(3-) and fibroblast growth factor (FGF) 23 as well as Fgf23 mRNA expression in bone. In conclusion, circulating 1,25(OH)(2) D(3) is important for optimal control of Ca(2+) homeostasis but also for controlled bone formation and matrix mineralization.

  14. Partial Removal of Pore and Loosely Bound Water by Low-Energy Drying Decreases Cortical Bone Toughness in Young and Old Donors

    PubMed Central

    Nyman, Jeffry S.; Gorochow, Lacey E.; Horch, R. Adam; Uppuganti, Sasidhar; Zein-Sabatto, Ahbid; Manhard, Mary Katherine; Does, Mark D.

    2012-01-01

    With an ability to quantify matrix-bound and pore water in bone, 1H nuclear magnetic resonance (NMR) relaxometry can potentially be implemented in clinical imaging to assess the fracture resistance of bone in a way that is independent of current X-ray techniques, which assess bone mineral density as a correlate of bone strength. Working towards that goal, we quantified the effect of partial dehydration in air on the mechanical and NMR properties of human cortical bone in order to understand whether NMR is sensitive to water-bone interactions at low energy and whether such interactions contribute to the age-related difference in the toughness of bone. Cadaveric femurs were collected from male and female donors falling into two age groups: 21 to 60 years of age (young) and 74 to 99 years of age (old). After extracting two samples from the medial cortex of the mid-shaft, tensile tests were conducted on Wet specimens and paired, Partially Dry (PtlD) specimens (prepared by low-energy drying in air to remove ~3% of original mass before testing). Prior analysis by micro-computed tomography found that there were no differences in intra-cortical porosity between the Wet and PtlD specimens nor did an age-related difference in porosity exist. PtlD specimens from young and old donors had significantly less toughness than Wet specimens, primarily due to a dehydration-related decrease in post-yield strain. The low-energy drying protocol did not affect the modulus and yield strength of bone. Subsequent dehydration of the PtlD specimens in a vacuum oven at 62 °C and then 103 °C, with quantification of water loss at each temperature, revealed an age-related shift from more loosely bound water to more tightly bound water. NMR detected a change in both bound and pore water pools with low-energy air-drying, and both pools were effectively removed when bone was oven-dried at 62 °C, irrespective of donor age. Although not strictly significant due to variability in the drying and

  15. Activation of matrix metalloproteinase-9 is associated with mobilization of bone marrow-derived cells after coronary stent implantation.

    PubMed

    Inoue, Teruo; Taguchi, Isao; Abe, Shichiro; Toyoda, Shigeru; Nakajima, Kohsuke; Sakuma, Masashi; Node, Koichi

    2011-11-03

    After stent-related vascular injury, an inflammatory response triggers the mobilization of bone marrow-derived stem cells, including both endothelial and smooth muscle progenitors, leading to re-endothelialization as well as restenosis. It has been postulated that neutrophil-released matrix metalloproteinase-9 (MMP-9) induces stem cell mobilization. To elucidate the mechanistic link between inflammation and stem cell mobilization after coronary stenting. In 31 patients undergoing coronary stenting, we serially measured activated Mac-1 on the surface of neutrophils and active MMP-9 levels in the coronary sinus blood plasma, and the number of circulating CD34-positive cells in the peripheral blood. After bare-metal stent implantation (n=21), significant increases in the numbers of CD34-positive cells (maximum on post-procedure day 7, P<0.001), activated Mac-1 (at 48 h, P<0.001), and active MMP-9 levels (at 24h, P<0.001) were observed. However, these changes were absent after sirolimus-eluting stent implantation (n=10). In overall patients, the numbers of CD34-positive cells on day 7 (R=0.58, P<0.01) and activated Mac-1 at 48 h (R=0.58, P<0.01) were both correlated with active MMP-9 levels at 24h. Stimulation of activated Mac-1 on the surface of isolated human neutrophils produced active MMP-9 release in vitro. These results suggest that stent-induced activation of Mac-1 on the surface of neutrophils might trigger their MMP-9 release, possibly leading to the mobilization of bone marrow-derived stem cells. These reactions were substantially inhibited by sirolimus-eluting stents. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Unsaturation level decreased in bone marrow fat of postmenopausal women with low bone density using high resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy.

    PubMed

    Li, Xiaojuan; Shet, Keerthi; Xu, Kaipin; Rodríguez, Juan Pablo; Pino, Ana María; Kurhanewicz, John; Schwartz, Ann; Rosen, Clifford J

    2017-08-18

    There are increasing evidences suggesting bone marrow adiposity tissue (MAT) plays a critical role in affecting both bone quantity and quality. However, very limited studies that have investigated the association between the composition of MAT and bone mineral density (BMD). The goal of this study was to quantify MAT unsaturation profile of marrow samples from post-menopausal women using ex vivo high-resolution magic angle spinning (HRMAS) proton nuclear magnetic resonance ((1)H NMR) spectroscopy, and to investigate the relationship between MAT composition and BMD. Bone marrow samples were obtained by iliac crest aspiration during surgical procedures from 24 postmenopausal women (65-89years) who had hip surgery due to bone fracture or arthroplasty. Marrow fat composition parameters, in particular, unsaturation level (UL), mono-unsaturation level (MUL) and saturation level (SL), were quantified using HRMAS (1)H NMR spectroscopy. The patients were classified into three groups based on the DXA BMD T-scores: controls, osteopenia and osteoporosis. Marrow fat composition was compared between these three groups as well as between subjects with and without factures using ANOCOVA, adjusted for age. Subjects with lower BMD (n=17) had significantly lower MUL (P=0.003) and UL (P=0.039), and significantly higher SL (P=0.039) compared to controls (n=7). When separating lower BMD into osteopenia (n=9) and osteoporosis (n=8) groups, subjects with osteopenia had significantly lower MUL (P=0.002) and UL (P=0.010), and significantly higher SL (P=0.010) compared to healthy controls. No significant difference was observed between subjects with osteopenia and osteoporosis. Using HRMAS (1)H NMR, significantly lower unsaturation and significantly higher saturation levels were observed in the marrow fat of subjects with lower BMD. HRMAS (1)H NMR was shown to be a powerful tool for identifying novel MR markers of marrow fat composition that are associated with bone quality and potentially

  17. Does 12 weeks of regular standing prevent loss of ankle mobility and bone mineral density in people with recent spinal cord injuries?

    PubMed

    Ben, Marsha; Harvey, Lisa; Denis, Sophie; Glinsky, Joanne; Goehl, Gerlinde; Chee, Shane; Herbert, Robert D

    2005-01-01

    The purpose of this study was to determine the effects of a 12-week standing program on ankle mobility and femur bone mineral density in patients with lower limb paralysis following recent spinal cord injury. An assessor-blinded within-subject randomised controlled trial was undertaken. Twenty patients with lower limb paralysis following a recent spinal cord injury were recruited. Subjects stood weight-bearing through one leg on a tilt-table for 30 minutes, three times each week for 12 weeks. By standing on one leg a large dorsiflexion stretch was applied to the ankle and an axial load was applied to the bones of the weight-bearing leg. Ankle mobility and femur bone mineral density of both legs were measured at the beginning and end of the study. Ankle mobility (range of motion) was measured with the application of a 17 Nm dorsiflexion torque. Femur bone mineral density was measured using dual energy X-ray absorptiometry (DEXA). The effect of standing was estimated from the difference between legs in mean change of ankle mobility and femur bone mineral density. The results indicated a mean treatment effect on ankle mobility of 4 degrees (95% CI 2 to 6 degrees) and on femur bone mineral density of 0.005 g/cm(2) (95% CI -0.015 to 0.025 g/cm(2)). Tilt-table standing for 30 minutes, three times per week for 12 weeks has a small effect on ankle mobility, and little or no effect on femur bone mineral density. It is unclear whether clinicians and patients would consider such effects to be clinically worthwhile.

  18. Development and Efficacy Testing of a "Hollow Awl" That Leads to Patent Bone Marrow Channels and Greater Mesenchymal Stem Cell Mobilization During Bone Marrow Stimulation Cartilage Repair Surgery.

    PubMed

    Min, Byoung-Hyun; Truong, Minh-Dung; Song, Hyung Keun; Cho, Jae Ho; Park, Do Young; Kweon, Heon Ju; Chung, Jun Young

    2017-08-16

    To investigate whether microfracture with a cannulated hollow awl can yield more patent marrow channels and allow greater mobilization of the reparable cells to the defect compared to the conventional awl with blunt end in human knee joints. Patients who were planned for 1-stage bilateral total knee arthroplasty due to degenerative osteoarthritis with well-preserved lateral femoral condylar cartilage were retrospectively included. A 10-mm × 20-mm, rectangular, full-thickness chondral defect was made on the lateral femoral condyle on each knee joint. The 6-holed microfracture procedure, each at 9 mm depth and 3 mm separation of perforations, was followed using a hollow awl in one knee and using a conventional awl in the other knee, respectively. The bleeding through the microfracture holes was observed and collected using an absorbable gelatin sponge and was analyzed microscopically by colony forming unit-fibroblast assays and automated cell counting method. The representative 3 bony samples of the distal lateral femoral condyles obtained were also scanned with micro-computed tomography (micro-CT) for morphometric analysis (percent bone volume, trabecular separation, and total porosity) of subchondral bone microarchitecture of the microfracture holes. Twenty-two patients were enrolled, and the mean age was 70.8 ± 6.1 (58-83) years. Compared with the conventional awl group, the hollow awl group had a significantly greater amount of bleeding (1.8 ± 0.2 g vs 1.1 ± 0.1 g; P < .001) and a greater number of mesenchymal stem cells in the blood clot (21,474.0 ± 3,911.1 vs 13,329.7 ± 3,311.0; P = .004). The hollow awl group also showed overall more patent marrow channels around the adjacent subchondral bone of the microfracture hole, with greater trabecular separation on micro-CT analysis (P < .001). Compared to the conventional awl, microfracture with a cannulated hollow awl can yield more patent marrow channels at the adjacent subchondral bone of the

  19. Genetic risk factors for decreased bone mineral accretion in children with asthma receiving multiple oral corticosteroid bursts

    PubMed Central

    Park, Heung-Woo; Ge, Bing; Tse, Szeman; Grundberg, Elin; Pastinen, Tomi; Kelly, H. William; Tantisira, Kelan G.

    2015-01-01

    Introduction Long-term, intermittent oral corticosteroid (OCS) use in children with asthma leads to significant decrements in bone mineral accretion (BMA). We aimed to identify genetic factors influencing OCS dose effects on BMA in children with asthma. Methods We first performed a gene by OCS interaction genome-wide association study (GWAS) of BMA in 489 white participants in the Childhood Asthma Management Program trial, who took short-term oral prednisone bursts when they experienced acute asthma exacerbations. We selected the top-ranked 2,000 single nucleotide polymorphisms (SNPs) in the GWAS and determined whether these SNPs also had cis-regulatory effects on dexamethasone-induced gene expression in osteoblast cells. Results We identified two SNPs (rs9896933 and rs2074439) associated with decreased BMA and related to the tubulin γ pathway. Rs9896933 met criteria for genome-wide significance (P = 3.15 ×10−8 in GWAS) and is located on the intron of tubulin folding cofactor D gene. Rs2074439 (P = 2.74 × 10−4 in GWAS) showed strong cis-regulatory effects on dexamethasone-induced tubulin γ gene expression in osteoblast cells (P = 8.64 × 10−4). Interestingly, we found that BMA worsened with increased dose of prednisone as the number of mutant alleles of the two SNPs increased. Conclusions We have identified two novel tubulin γ pathway SNPs, rs9896933 and rs2074439, showing independent interactive effects with cumulative corticosteroid dose on BMA in children with asthma receiving multiple OCS bursts. PMID:26025128

  20. Specifically decreased collagen biosynthesis in scurvy dissociated from an effect on proline hydroxylation and correlated with body weight loss. In vitro studies in guinea pig calvarial bones.

    PubMed Central

    Chojkier, M; Spanheimer, R; Peterkofsky, B

    1983-01-01

    The question whether ascorbate regulates collagen production solely through its direct role in proline hydroxylation was investigated. Proteins in calvarial bones from control and scorbutic weanling guinea pigs were labeled in short-term cultures with radioactive proline. Proteins were digested with purified bacterial collagenase to distinguish between effects on collagen polypeptide production and hydroxyproline formation. There was a preferential decrease in the absolute rate of collagen biosynthesis beginning after 2 wk of ascorbate deficiency, and this effect was temporally dissociated from decreased proline hydroxylation. There were no significant changes in the absolute rates of collagen degradation or noncollagen protein production. In vitro inhibition of proline hydroxylation in normal bone with alpha, alpha'-dipyridyl did not affect the relative rate of collagen synthesis, further dissociating these functions. Ascorbate added to scorbutic bone cultures reversed defective proline hydroxylation but not defective collagen synthesis, suggesting that the latter was an indirect effect of scurvy. There was a linear correlation between the extent of body weight lost during the 3rd and 4th wk of scurvy and the rate of collagen synthesis in scorbutic bone. This correlation also applied to control animals receiving ascorbate, but with weight loss induced by food restriction. These studies establish for the first time that ascorbate deficiency in guinea pigs leads to a specific decrease in collagen polypeptide synthesis and suggest that this decrease results from the reduced food intake and/or weight-loss characteristic of scurvy. Images FIGURE 1 PMID:6309911

  1. Reduced Intranuclear Mobility of APL Fusion Proteins Accompanies Their Mislocalization and Results in Sequestration and Decreased Mobility of Retinoid X Receptor α

    PubMed Central

    Dong, Shuo; Stenoien, David L.; Qiu, Jihui; Mancini, Michael A.; Tweardy, David J.

    2004-01-01

    Acute promyelocytic leukemia (APL) cells contain one of five chimeric retinoic acid α-receptor (RARα) genes (X-RARα) created by chromosomal translocations or deletion; each generates a fusion protein thought to transcriptionally repress RARα target genes and block myeloid differentiation by an incompletely understood mechanism. To gain spatiotemporal insight into these oncogenic processes, we employed fluorescence microscopy and fluorescence recovery after photobleaching (FRAP). Fluorescence microscopy demonstrated that the intracellular localization of each of the X-RARα proteins was distinct from that of RARα and established which portion(s) of each X-RARα protein—X, RAR, or both—contributed to its altered localization. Using FRAP, we demonstrated that the intranuclear mobility of each X-RARα was reduced compared to that of RARα. In addition, the mobility of each X-RARα was reduced further by ligand addition, in contrast to RARα, which showed no change in mobility when ligand was added. Both the reduced baseline mobility of X-RARα and the ligand-induced slowing of X-RARα could be attributed to the protein interaction domain contained within X. RXRα aberrantly colocalized within each X-RARα; colocalization of RXRα with promyelocytic leukemia (PML)-RARα resulted in reduced mobility of RXRα. Thus, X-RARα may interfere with RARα through its aberrant nuclear dynamics, resulting in spatial and temporal sequestration of RXRα and perhaps other nuclear receptor coregulators critical for myeloid differentiation. PMID:15121864

  2. Bone Marrow Homing Enriches Stem Cells Responsible for Neogenesis of Insulin-Producing Cells, While Radiation Decreases Homing Efficiency.

    PubMed

    Goldenberg-Cohen, Nitza; Iskovich, Svetlana; Askenasy, Nadir

    2015-10-01

    Small-sized adult bone marrow cells isolated by counterflow centrifugal elutriation and depleted of lineage markers (Fr25lin(-)) have the capacity to differentiate into insulin-producing cells and stabilize glycemic control. This study assessed competitive migration of syngeneic stem cells to the bone marrow and islets in a murine model of chemical diabetes. VLA-4 is expressed in ∼ 25% of these cells, whereas CXCR4 is not detected, however, it is transcriptionally upregulated (6-fold). The possibility to enrich stem cells by a bone marrow homing (BM-H) functional assay was assessed in sequential transplants. Fr25lin(-) cells labeled with PKH26 were grafted into primary myeloablated recipients, and mitotically quiescent Fr25lin(-)PKH(bright) cells were sorted from the bone marrow after 2 days. The contribution of bone marrow-homed stem cells was remarkably higher in secondary recipients compared to freshly elutriated cells. The therapeutic efficacy was further increased by omission of irradiation in the secondary recipients, showing a 25-fold enrichment of islet-reconstituting cells by the bone marrow homing assay. Donor cells identified by the green fluorescent protein (GFP) and a genomic marker in sex-mismatched transplants upregulated PDX-1 and produced proinsulin, affirming the capacity of BM-H cells to convert in the injured islets. There was no evidence of transcriptional priming of freshly elutriated subsets to express PDX-1, insulin, and other markers of endocrine progenitors, indicating that the bone marrow harbors stem cells with versatile differentiation capacity. Affinity to the bone marrow can be used to enrich stem cells for pancreatic regeneration, and reciprocally, conditioning reduces the competitive incorporation in the injured islets.

  3. Can Technology Decrease Sexual Risk Behaviors among Young People? Results of a Pilot Study Examining the Effectiveness of a Mobile Application Intervention

    ERIC Educational Resources Information Center

    Jackson, Dawnyéa D.; Ingram, Lucy Annang; Boyer, Cherrie B.; Robillard, Alyssa; Huhns, Michael N.

    2016-01-01

    College students represent an important population for studying and understanding factors that influence sexual risk given the populations' high risk of sexually transmitted infections and unintended pregnancies. Using a quasi-experimental design, the efficacy of a brief and theory-driven mobile application intervention designed to decrease sexual…

  4. Can Technology Decrease Sexual Risk Behaviors among Young People? Results of a Pilot Study Examining the Effectiveness of a Mobile Application Intervention

    ERIC Educational Resources Information Center

    Jackson, Dawnyéa D.; Ingram, Lucy Annang; Boyer, Cherrie B.; Robillard, Alyssa; Huhns, Michael N.

    2016-01-01

    College students represent an important population for studying and understanding factors that influence sexual risk given the populations' high risk of sexually transmitted infections and unintended pregnancies. Using a quasi-experimental design, the efficacy of a brief and theory-driven mobile application intervention designed to decrease sexual…

  5. Decreased bone turnover markers in children on long-term parenteral nutrition (PN) for intestinal failure (IF).

    PubMed

    Derepas, Charlène; Kosar, Christina; Avitzur, Yaron; Wales, Paul W; Courtney-Martin, Glenda

    2015-01-01

    Metabolic bone disease (MBD) is a well-recognized but poorly understood complication of long-term parenteral nutrition (PN). Bone histomorphometry in adults has provided useful information but does not provide quantitative measures of bone resorption and is to invasive for children. Measurement of bone turnover markers provides an alternative less invasive approach. We therefore aimed to measure bone turnover markers in children on long-term PN for intestinal failure (IF), and to compare them to age- and gender-matched controls. Serum concentrations of osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and c-telopeptide (CTx) were measured in IF patients treated at a multidisciplinary intestinal rehabilitation and home PN program at the Hospital for Sick Children, Toronto, Canada. Age- and gender-matched control participants were recruited for comparison. A total of 13 IF patients and 20 control participants were recruited. IF patients had lower serum OC and CTx concentrations when compared with controls: 42.43 ± 11.54 vs 68.39 ± 20.95 µg/L (P < .01) and 7.454 ± 2.17 vs 9.246 ± 1.92 (P < .05; mean ± SD) µg/L for OC and CTx, respectively. In a subgroup of 9 IF patients for whom BMD was available, OC and CTx concentration were negatively correlated to BMD (g/cm(2)) and BMD z score. Bone turnover markers may be useful indicators for identifying children on long-term PN at risk of MBD. Further studies are needed to validate the current results and determine the factors that influence the occurrence and evolution of MBD in children on PN. © 2013 American Society for Parenteral and Enteral Nutrition.

  6. Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: a basic science study

    PubMed Central

    Tat, Steeve Kwan; Pelletier, Jean-Pierre; Vergés, Josep; Lajeunesse, Daniel; Montell, Eulàlia; Fahmi, Hassan; Lavigne, Martin; Martel-Pelletier, Johanne

    2007-01-01

    Early in the pathological process of osteoarthritis (OA), subchondral bone remodelling, which is related to altered osteoblast metabolism, takes place. In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the pro-resorptive activity of OA osteoblasts. The effect of CS (200 μg/mL), GS (50 and 200 μg/mL), or both together on human OA subchondral bone osteoblasts, in the presence or absence of 1,25(OH)2D3 (vitamin D3) (50 nM), was determined on the bone biomarkers alkaline phosphatase and osteocalcin, on the expression (mRNA) and production (enzyme-linked immunosorbent assay) of bone remodelling factors OPG and RANKL, and on the pro-resorptive activity of these cells. For the latter experiments, human OA osteoblasts were incubated with differentiated peripheral blood mononuclear cells on a sub-micron synthetic calcium phosphate thin film. Data showed that CS and GS affected neither basal nor vitamin D3-induced alkaline phosphatase or osteocalcin release. Interestingly, OPG expression and production under basal conditions or vitamin D3 treatment were upregulated by CS and by both CS and GS incubated together. Under basal conditions, RANKL expression was significantly reduced by CS and by both drugs incubated together. Under vitamin D3, these drugs also showed a decrease in RANKL level, which, however, did not reach statistical significance. Importantly, under basal conditions, CS and both compounds combined significantly upregulated the expression ratio of OPG/RANKL. Vitamin D3 decreased this ratio, and GS further decreased it. Both drugs reduced the resorption activity, and statistical significance was reached for GS and when CS and GS were incubated together. Our data indicate that CS and GS do not overly affect cell integrity or bone biomarkers. Yet CS and

  7. Propranolol, a β-adrenergic antagonist, attenuates the decrease in trabecular bone mass in high calorie diet fed growing mice

    PubMed Central

    Baek, Kyunghwa; Hwang, Hyo Rin; Park, Hyun-Jung; Kwon, Arang; Qadir, Abdul S.; Baek, Jeong-Hwa

    2014-01-01

    We investigated the effects of high calorie and low calorie diets on skeletal integrity, and whether β-adrenergic blockade (BB) attenuates bone loss induced by dietary calorie alteration. Male 6-week-old C57BL/6 mice were assigned to either an ad-lib fed control diet (CON), a high calorie diet (HIGH), or a low calorie diet (LOW) group. In each diet group, mice were treated with either vehicle (VEH) or propranolol, a β-adrenergic antagonist. Over 12-weeks, β-blockade mitigated body weight and fat mass increases induced by the high calorie diet. Femoral trabecular bone mineral density and the expression levels of osteogenic marker genes in bone marrow cells were reduced in HIGHVEH and LOWVEH mice, and BB significantly attenuated this decline only in HIGH mice. In summary, the magnitude of bone loss induced by low calorie diet was greater than that caused by high calorie diet in growing mice, and β-blockade mitigated high calorie diet-induced bone loss. [BMB Reports 2014; 47(9): 506-511] PMID:24393528

  8. Propranolol, a β-adrenergic antagonist, attenuates the decrease in trabecular bone mass in high calorie diet fed growing mice.

    PubMed

    Baek, Kyunghwa; Hwang, Hyo Rin; Park, Hyun-Jung; Kwon, Arang; Qadir, Abdul S; Baek, Jeong-Hwa

    2014-09-01

    We investigated the effects of high calorie and low calorie diets on skeletal integrity, and whether β-adrenergic blockade (BB) attenuates bone loss induced by dietary calorie alteration. Male 6-week-old C57BL/6 mice were assigned to either an ad-lib fed control diet (CON), a high calorie diet (HIGH), or a low calorie diet (LOW) group. In each diet group, mice were treated with either vehicle (VEH) or propranolol, a β-adrenergic antagonist. Over 12-weeks, β-blockade mitigated body weight and fat mass increases induced by the high calorie diet. Femoral trabecular bone mineral density and the expression levels of osteogenic marker genes in bone marrow cells were reduced in HIGHVEH and LOWVEH mice, and BB significantly attenuated this decline only in HIGH mice. In summary, the magnitude of bone loss induced by low calorie diet was greater than that caused by high calorie diet in growing mice, and β-blockade mitigated high calorie diet-induced bone loss.

  9. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    SciTech Connect

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  10. Bone density of the greater tuberosity is decreased in rotator cuff disease with and without full-thickness tears.

    PubMed

    Waldorff, Erik I; Lindner, James; Kijek, Theresa G; Downie, Brian K; Hughes, Richard E; Carpenter, James E; Miller, Bruce S

    2011-09-01

    Despite the high prevalence of rotator cuff disease in the aging adult population, the basic mechanisms initiating the disease are not known. It is known that changes occur at both the bone and tendon after rotator cuff tears. However, no study has focused on early or "pretear" rotator cuff disease states. The purpose of this study was to compare the bone mineral density of the greater tuberosity in normal subjects with that in subjects with impingement syndrome and full-thickness rotator cuff tears. Digital anteroposterior shoulder radiographs were obtained for 3 sex- and age-matched study groups (men, 40-70 years old): normal asymptomatic shoulders (control), rotator cuff disease without full-thickness tears (impingement), and full-thickness rotator cuff tears (n = 39 per group). By use of imaging software, bone mineral densities were determined for the greater tuberosity, the greater tuberosity cortex, the greater tuberosity subcortex, and the cancellous region of the humeral head. The bone mineral density of the greater tuberosity was significantly higher for the normal control subjects compared with subjects with impingement or rotator cuff tears. No differences were found between the two groups of patients with known rotator cuff disease. The greater tuberosity cortex and greater tuberosity subcortex outcome measures were similar. Bone mineral changes are present in the greater tuberosity of shoulders with rotator cuff disease both with and without full-thickness tears. The finding of focal diminished bone mineral density of the greater tuberosity in the absence of rotator cuff tears warrants further investigation. Copyright © 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  11. Transforming growth factor (TGF. beta. ) decreases the proliferation of human bone marrow fibroblasts by inhibiting the platelet-derived growth factor (PDGF) binding

    SciTech Connect

    Bryckaert, M.C.; Tobelem, G. ); Lindroth, M.; Loenn, A.; Wasteson, A. )

    1988-12-01

    Human bone marrow fibroblasts were cultivated and characterized by immunofluorescent staining and electron microscopy. Their interactions with PDGF and TGF{beta} were studied. While a positive intracellular antifibronectin staining was observed, the cultured cells were not labeled with specific antibodies toward factor VIII von Willebrand factor (F VIII/vWF), desmin, and macrophage antigen. The binding of pure human PDGF to the cultured bone marrow fibroblasts was investigated. Addition of an excess of unlabeled PDGF decreased the binding to 75 and 80%, which means that the nonspecific binding represented 20-25% of total binding, whereas epidermal growth factor (EGF) had no effect. Two classes of sites were detected by Scatchard analysis. The stimulation of DNA synthesis of PDGF was quantified by ({sup 3}H)thymidine incorporation. The results suggested that PDGF and TGF{beta} could modulate the growth of bone marrow fibroblasts.

  12. Sex-specific compromised bone healing in female rats might be associated with a decrease in mesenchymal stem cell quantity.

    PubMed

    Strube, Patrick; Mehta, Manav; Baerenwaldt, Anne; Trippens, Jessica; Wilson, Cameron J; Ode, Andrea; Perka, Carsten; Duda, Georg N; Kasper, Grit

    2009-12-01

    The clinically known importance of patient sex as a major risk factor for compromised bone healing is poorly reflected in animal models. Consequently, the underlying cellular mechanisms remain elusive. Because mesenchymal stem cells (MSCs) are postulated to regulate tissue regeneration and give rise to essential differentiated cell types, they may contribute to sex-specific differences in bone healing outcomes. We investigated sex-specific variations in bone healing and associated differences in MSC populations. A 1.5 mm osteotomy gap in the femora of 8 male and 8 female 12-month-old Sprague-Dawley rats was stabilized by an external fixator. Healing was analyzed in terms of biomechanical testing, bridging and callus size over time (radiography at 2, 4, and 6 weeks after surgery), and callus volume and geometry by microCT at final follow-up. MSCs were obtained from bone marrow samples of an age-matched group of 12 animals (6 per gender) and analyzed for numbers of colony-forming units (CFUs) and their capacity to differentiate and proliferate. The proportion of senescent cells was determined by beta-galactosidase staining. Sex-specific differences were indicated by a compromised mechanical competence of the callus in females compared with males (maximum torque at failure, p=0.028). Throughout the follow-up, the cross-sectional area of callus relative to bone was reduced in females (p< or =0.01), and the bridging of callus was delayed (p(2weeks)=0.041). microCT revealed a reduced callus size (p=0.003), mineralization (p=0.003) and polar moment of inertia (p=0.003) in female animals. The female bone marrow contained significantly fewer MSCs, represented by low CFU numbers in both femora and tibiae (p(femur)=0.017, p(tibia)=0.010). Functional characteristics of male and female MSCs were similar. Biomechanically compromised and radiographically delayed bone formation were distinctive in female rats. These differences were concomitant with a reduced number of MSCs, which

  13. Dietary zinc supplementation increased TNFα and IL1β-induced RANKL expression, resulting in a decrease in bone mineral density in rats

    PubMed Central

    Suzuki, Takako; Katsumata, Shin-ichi; Matsuzaki, Hiroshi; Suzuki, Kazuharu

    2016-01-01

    We investigated the effect of dietary zinc supplementation on bone metabolism in rats. Four-week-old male Wistar rats were fed a 30.0 mg zinc/kg diet (C), a 300.0 mg zinc/kg diet (HZ) or a 3,000.0 mg zinc/kg diet (EZ) for 4 weeks. The zinc content of the femur gradually increased in accordance with the gradual increase in the dietary zinc level. Although the mRNA expression of zinc transporters in bone did not differ between the groups, the mRNA expression of metallothioneins was increased in the HZ and EZ groups compared to the C group. Moreover, the bone mineral density was significantly decreased in the HZ and EZ groups compared to the C group. Furthermore, the mRNA expression of tumor necrosis factor α, Interleukin-1β and osteoclastogenesis-related genes such as receptor for activator of nuclear factor-κB (NF-κB) ligand, tumor necrosis factor receptor-associated factor 6, and nuclear factor of activated T cells cytoplasmic 1 was significantly increased in the HZ and EZ groups compared to the C group. These findings suggested that dietary zinc supplementation reduced bone mineral density through the promotion of bone resorption via an increase in the expression of receptor for activator of NF-κB ligand induced by tumor necrosis factor α and Interleukin-1β. PMID:26798197

  14. Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3.

    PubMed

    Bhandaru, Madhuri; Kempe, Daniela S; Rotte, Anand; Capuano, Paola; Pathare, Ganesh; Sopjani, Mentor; Alesutan, Ioana; Tyan, Leonid; Huang, Dan Yang; Siraskar, Balasaheb; Judenhofer, Martin S; Stange, Gerti; Pichler, Bernd J; Biber, Jürg; Quintanilla-Martinez, Leticia; Wagner, Carsten A; Pearce, David; Föller, Michael; Lang, Florian

    2011-07-01

    Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. Coexpression of SGK3 and sodium-phosphate cotransporter IIa significantly enhanced the phosphate-induced current in Xenopus oocytes. In sgk3 knockout and wild-type mice on a standard diet, fluid intake, glomerular filtration and urine flow rates, and urinary calcium ion excretion were similar. However, fractional urinary phosphate excretion was slightly but significantly larger in the knockout than in wild-type mice. Plasma calcium ion, phosphate concentration, and plasma parathyroid hormone levels were not significantly different between the two genotypes, but plasma calcitriol and fibroblast growth factor 23 concentrations were significantly lower in the knockout than in wild-type mice. Moreover, bone density was significantly lower in the knockouts than in wild-type mice. Histological analysis of the femur did not show any differences in cortical bone but there was slightly less prominent trabecular bone in sgk3 knockout mice. Thus, SGK3 has a subtle but significant role in the regulation of renal tubular phosphate transport and bone density.

  15. Borage and fish oils lifelong supplementation decreases inflammation and improves bone health in a murine model of senile osteoporosis.

    PubMed

    Wauquier, Fabien; Barquissau, Valentin; Léotoing, Laurent; Davicco, Marie-Jeanne; Lebecque, Patrice; Mercier, Sylvie; Philippe, Claire; Miot-Noirault, Elisabeth; Chardigny, Jean-Michel; Morio, Béatrice; Wittrant, Yohann; Coxam, Véronique

    2012-02-01

    Fats are prevalent in western diets; they have known deleterious effects on muscle insulin resistance and may contribute to bone loss. However, relationships between fatty acids and locomotor system dysfunctions in elderly population remain controversial. The aim of this study was to analyze the impact of fatty acid quality on the age related evolution of the locomotor system and to understand which aging mechanisms are involved. In order to analyze age related complications, the SAMP8 mouse strain was chosen as a progeria model as compared to the SAMR1 control strain. Then, two months old mice were divided in different groups and subjected to the following diets : (1) standard "growth" diet - (2) "sunflower" diet (high ω6/ω3 ratio) - (3) "borage" diet (high γ-linolenic acid) - (4) "fish" diet (high in long chain ω3). Mice were fed ad libitum through the whole protocol. At 12 months old, the mice were sacrificed and tissues were harvested for bone studies, fat and muscle mass measures, inflammation parameters and bone cell marker expression. We demonstrated for the first time that borage and fish diets restored inflammation and bone parameters using an original model of senile osteoporosis that mimics clinical features of aging in humans. Therefore, our study strongly encourages nutritional approaches as relevant and promising strategies for preventing aged-related locomotor dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.

    PubMed

    Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

    2002-11-01

    Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms.

  17. Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells

    PubMed Central

    Kalinkovich, Alexander; Itkin, Tomer; Ludin, Aya; Kao, Wei-Ming; Battista, Michela; Tesio, Melania; Kollet, Orit; Cohen, Neta Netzer; Margalit, Raanan; Buss, Eike C.; Baleux, Francoise; Oishi, Shinya; Fujii, Nobutaka; Larochelle, Andre; Dunbar, Cynthia E.; Broxmeyer, Hal E.; Frenette, Paul S.; Lapidot, Tsvee

    2014-01-01

    Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine SDF-1 to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady-state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4+ human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, while β2-adrenergic antagonist inhibited both steady-state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes. PMID:21494253

  18. Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels.

    PubMed

    Kaufman, Becky A; Warren, Michelle P; Dominguez, Jennifer E; Wang, Jack; Heymsfield, Steven B; Pierson, Richard N

    2002-06-01

    Osteopenia, which is correlated with amenorrhea and poor nutritional habits, has been well documented in elite ballet dancers. Estrogen replacement therapy and recovery from amenorrhea have not been associated with normalization of bone density. Thus, the osteopenia may be related to changes brought about by chronic dieting or other factors, such as a hypometabolic state induced by poor nutrition. The purpose of this study was to investigate the relationship of chronic dieting and resting metabolic rate (RMR) to amenorrhea and bone density. RMR, bone density, eating disorder assessments, leptin levels, and complete menstrual and medical histories were determined in 21 elite ballet dancers and in 27 nondancers (age, 20-30 yr). No significant correlations were found between high EAT26 scores, a measure of disordered eating, and RMR, bone densities, body weight, body fat, or fat-free mass. However, when RMR was adjusted for fat-free mass (FFM), a significant positive correlation was found between RMR/FFM and bone density in both the arms (P < 0.001) and spine (P < 0.05) in ballet dancers, but not in the normal controls. The dancers also demonstrated significantly higher EAT scores (22.9 +/- 10.3 vs. 4.1 +/- 2.4; P < 0.001) and lower RMR/FFM ratios (30.0 +/- 2.2 vs. 32.05 +/- 2.8; P < 0.01). The only variable to predict lower RMR/FFM in the entire sample was ever having had amenorrhea; this group had significantly higher EAT scores (18.0 +/- 13.5 vs. 10.3 +/- 10.2; P < 0.05), lower leptin levels (4.03 +/- 0.625 vs. 7.10 +/- 4.052; P < 0.05), and lower bone mineral density in the spine (0.984 +/- 0.11 vs. 1.10 +/- 0.13; P < 0.05) and arm (0.773 +/- 0.99 vs. 0.818 +/- 0.01; P < 0.05). We hypothesize that the correlation between low RMR and lower leptin levels and bone density may be more strongly related to nutritional habits in ballet dancers, causing significant depression of RMR, particularly for those with a history of amenorrhea.

  19. Multiple exposures to unloading decrease bone's responsivity but compound skeletal losses in C57BL/6 mice

    PubMed Central

    Gupta, Shikha; Vijayaraghavan, Surabhi; Uzer, Gunes

    2012-01-01

    A single exposure to mechanical unloading can result in significant bone loss, but the consequences of multiple exposures are largely unknown. Within a 18-wk period, adult C57BL/6 male mice were exposed to 2 wk of hindlimb unloading (HLU) followed by 4 wk of reambulation (RA) once (1x-HLU), twice (2x-HLU), or three times (3x-HLU), or served as ambulatory age-matched controls. In vivo μCT longitudinally tracked changes in trabecular and cortical compartments of the femur. Normally ambulating control mice experienced significant age-related loss in trabecular bone volume fraction throughout the course of the experiment. This loss was compounded by HLU with 2x- and 3x-HLU mice experiencing a 27% and 24% greater reduction in trabecular bone and a 60% and 63% inhibition of age-related trabecular thickening. The recovery of cortical bone was also incomplete during each 4-wk RA period and, at completion of the experiment, cortical area in 3x-HLU mice was 5% smaller than in control and 1x-HLU. When eliminating age as a confounding variable, comparison between individual HLU/RA cycles showed that the magnitude of the response diminished during subsequent exposures. The extent of trabecular thinning in mice unloaded for the first time was 1.6-fold greater than the second time and nearly twofold greater than the third time. Similarly, the increase in trabecular thickness during the first RA cycle was twofold greater than during the second and third RA cycle. Together, our data demonstrate that even though multiple exposures to mechanical unloading are more detrimental than a single unloading period, bone's mechanosensitivity is reduced with consecutive unloading/reambulation cycles. PMID:22592559

  20. Roux-en-Y Gastric Bypass Surgery But Not Vertical Sleeve Gastrectomy Decreases Bone Mass in Male Rats

    PubMed Central

    Stemmer, Kerstin; Bielohuby, Maximilian; Grayson, Bernadette E.; Begg, Denovan P.; Chambers, Adam P.; Neff, Christina; Woods, Stephen C.; Erben, Reinhold G.; Tschöp, Matthias H.; Bidlingmaier, Martin; Clemens, Thomas L.

    2013-01-01

    The most effective treatment for obesity is bariatric surgery. However, there is increasing concern that bariatric surgery can cause nutrient deficiencies that translate into metabolic bone disease. Whether this is true for all surgery types is not yet clear. We therefore investigated the effects of 2 commonly applied bariatric surgeries (Roux-en-Y gastric bypass [RYGB] and vertical sleeve gastrectomy) on energy and bone metabolism in rats 60 days after surgery. Both surgeries resulted in similar reductions of body weight, body fat, and food intake. Glucose tolerance was improved to a similar extent after both surgeries and was accompanied by increased postprandial secretion of glucose-dependent insulinotropic peptide. Using microcomputed tomography, we found that, relative to sham-operated rats, bone volume was significantly reduced after RYGB but not vertical sleeve gastrectomy. RYGB rats also had markedly reduced lipid absorption from the intestine and significantly lower serum 25-hydroxyvitamin D and calcium levels. Importantly, dietary supplementation with calcium and vitamin D could not fully rescue the reduced bone volume after RYGB surgery. Both surgeries resulted in a significant increase in stomach pH, which may have worsened the malabsorption in RYGB rats. Our findings suggest that bone loss in RYGB rats is not exclusively driven by calcium and vitamin D malabsorption but also by additional factors that may not be rescuable by dietary supplementation. These data point toward important similarities and differences between bariatric procedures that should be considered in clinical settings as guidance for which procedure will be best for specific patient populations. PMID:23554454

  1. Tumor-derived microparticles induce bone marrow-derived cell mobilization and tumor homing: a process regulated by osteopontin.

    PubMed

    Fremder, Ella; Munster, Michal; Aharon, Anat; Miller, Valeria; Gingis-Velitski, Svetlana; Voloshin, Tali; Alishekevitz, Dror; Bril, Rotem; Scherer, Stefan J; Loven, David; Brenner, Benjamin; Shaked, Yuval

    2014-07-15

    Acute chemotherapy can induce rapid bone-marrow derived pro-angiogenic cell (BMDC) mobilization and tumor homing, contributing to tumor regrowth. To study the contribution of tumor cells to tumor regrowth following therapy, we focused on tumor-derived microparticles (TMPs). EMT/6 murine-mammary carcinoma cells exposed to paclitaxel chemotherapy exhibited an increased number of TMPs and significantly altered their angiogenic properties. Similarly, breast cancer patients had increased levels of plasma MUC-1(+) TMPs following chemotherapy. In addition, TMPs from cells exposed to paclitaxel induced higher BMDC mobilization and colonization, but had no increased effect on angiogenesis in Matrigel plugs and tumors than TMPs from untreated cells. Since TMPs abundantly express osteopontin, a protein known to participate in BMDC trafficking, the impact of osteopontin-depleted TMPs on BMDC mobilization, colonization, and tumor angiogenesis was examined. Although EMT/6 tumors grown in mice inoculated with osteopontin-depleted TMPs had lower numbers of BMDC infiltration and microvessel density when compared with EMT/6 tumors grown in mice inoculated with wild-type TMPs, no significant difference in tumor growth was seen between the two groups. However, when BMDCs from paclitaxel-treated mice were injected into wild-type EMT/6-bearing mice, a substantial increase in tumor growth and BMDC infiltration was detected compared to osteopontin-depleted EMT/6-bearing mice injected with BMDCs from paclitaxel-treated mice. Collectively, our results suggest that osteopontin expressed by TMPs play an important role in BMDC mobilization and colonization of tumors, but is not sufficient to enhance the angiogenic activity in tumors. © 2013 UICC.

  2. Mobilization

    DTIC Science & Technology

    1987-01-01

    istic and romantic emotionalism that typifies this genre. Longino, James C., et al. “A Study of World War Procurement and Industrial Mobilization...States. Harrisburg, PA: Military Service Publishing Co., 1941. CARL 355.22 J72b. Written in rough prose , this World War II era document explains the

  3. Decreased Amount of Supporting Alveolar Bone at Single-Rooted Premolars Is Under Estimated by 2D Examinations

    PubMed Central

    Hong, Hsiang-Hsi; Chang, Chung-Chieh; Hong, Adrienne; Liu, Heng-Liang; Wang, Yen-Li; Chang, Shih-Hao; Yen, Tzung-Hai

    2017-01-01

    The purpose of this study was to relate the proportions of bone-supported root length of a 2D view into the amount of a 3D bone-attached root surface area (BA-RSA) by using a dental laser scanner examination. White-light 3D scanning technology was used to probe 36 maxillary and 35 mandibular single-rooted premolars. The bone-supported height (BSH) and BA-RSA at designated levels (95–25%) were compared using statistical t tests. The 100% BSH and BA-RSA of the maxillary/mandibular premolars were 12.6 ± 1.60 mm/13.45 ± 1.47 mm (p < 0.05) and 220.78 ± 35.31 mm2/199.51 ± 26.33 mm2 (p < 0.01), respectively. Approximately 79–80%, 59–60%, and 35–36% premolars 2D BSH remained in comparison to 75%, 50%, and 25% 3D BA-RSA preservation, respectively. However, corresponding to a 75%, 50%, and 25% 2D BSH reserve, premolars retained 67–68%, 39–41%, and 15–17% 3D BA-RSA, respectively. When taking 1.0 mm connective tissue attachment into account, 60% 3D BA-RSA and 50% 2D BSH loss were noted at the 5.1–5.4 mm clinical attachment level. Assigning a periodontal prognosis and determining the severity of periodontitis for premolars with alveolar bone loss based on 3D’s or 2D’s measurement is inconsistent. PMID:28367999

  4. Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors

    PubMed Central

    2012-01-01

    Introduction Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression. Methods PGISp mice were characterised 12 weeks after initiation of inflammation using histology, immunohistochemistry (IHC) and expression profiling. Results Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated. Conclusions This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process. PMID:23171658

  5. Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors.

    PubMed

    Haynes, Katelin R; Pettit, Allison R; Duan, Ran; Tseng, Hsu-Wen; Glant, Tibor T; Brown, Matthew A; Thomas, Gethin P

    2012-11-22

    Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression. PGISp mice were characterised 12 weeks after initiation of inflammation using histology, immunohistochemistry (IHC) and expression profiling. Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated. This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process.

  6. Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae

    PubMed Central

    Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

    2002-01-01

    Background: Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. Objective: To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. Methods: 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). Results: s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Conclusions: Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms. PMID:12379520

  7. G-CSF for mobilizing transplanted bone marrow stem cells in rat model of Parkinson’s disease

    PubMed Central

    Safari, Manouchehr; Jafari, Behnaz; Zarbakhsh, Sam; Sameni, Hamidreza; Vafaei, Abbas Ali; Mohammadi, Nasrin Khan; Ghahari, Laya

    2016-01-01

    Objective(s):: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. Materials and Methods: We choose 25 male Wistar rats (200–250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc). G-CSF (70 µg/kg/day) was given from the 7th day after lesion for five days. The BMSCs (2×105) were injected through the dorsal tail vein on the 7th day after lesion. Results: The number of rotations was significantly lower in the stem cell therapy group than in the control group. In the third test in the received G-CSF and G-CSF+stem cells groups, animals displayed significant behavioral recovery compared with the control group (P<0.05). There was a significant difference in the average of dopaminergic neurons in SNpc between the control group and G-CSF and G-CS+stem cells groups. We didn’t detect any labeling stem cells in SNpc. Conclusion: G-CSF can’t mobilize low amounts of exogenous BMSCs from the blood stream to injured SNpc. But G-CSF (70 µg/kg) is more neuroprotective than BMSCs (2×105 number[w1] of BMSCs). Results of our study suggest that G-CSF alone is more neuroprotective than BMSCs. PMID:28096964

  8. Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo.

    PubMed

    Marycz, Krzysztof; Tomaszewski, Krzysztof A; Kornicka, Katarzyna; Henry, Brandon Michael; Wroński, Sebastian; Tarasiuk, Jacek; Maredziak, Monika

    2016-01-01

    Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine.

  9. Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo

    PubMed Central

    Marycz, Krzysztof; Tomaszewski, Krzysztof A.; Kornicka, Katarzyna; Henry, Brandon Michael; Wroński, Sebastian; Tarasiuk, Jacek; Maredziak, Monika

    2016-01-01

    Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine. PMID:27195075

  10. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

    PubMed

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

    2016-04-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure.

  11. The relationship between inert gas wash-out and radioactive tracer microspheres in measurement of bone blood flow: effect of decreased arterial supply and venous congestion on bone blood flow in an animal model.

    PubMed

    Kiaer, T; Dahl, B; Lausten, G S

    1993-01-01

    Several methods have been employed in the study of bone perfusion. We used a method of determining inert gas wash-out by mass spectrometry in the study of blood flow rates in pigs. The method was validated by comparison of the result obtained with inert gas wash-out to that with measurement by microspheres. Furthermore, the effect of decreased inlet flow and venous congestion on the bone perfusion data was tested. The undisturbed bone blood flow was not significantly different when measured with wash-out of inert gas (7 +/- 0.7 ml/min/100 g) or with microspheres (9 +/- 2.9 ml/min/100 g), and the methods were correlated. Perfusion was reduced significantly, to 20% of the original value, after arterial occlusion. The changes in wash-out curves and accumulation of radioactive tracer provided substantial evidence for impaired intraosseous circulation following venous obstruction also. In conclusion, the study showed that this method of determining inert gas wash-out is feasible for studies of local perfusion rates in bone. The flow rates obtained by wash-out correlated well with the results of microsphere studies. In this animal model, both methods detected a fivefold reduction in flow rate after clamping of the arterial inflow. Obstruction of the venous outflow also impaired blood flow and lowered the cellular supply.

  12. Direct Covalent Grafting of Phytate to Titanium Surfaces through Ti-O-P Bonding Shows Bone Stimulating Surface Properties and Decreased Bacterial Adhesion.

    PubMed

    Córdoba, Alba; Hierro-Oliva, Margarita; Pacha-Olivenza, Miguel Ángel; Fernández-Calderón, María Coronada; Perelló, Joan; Isern, Bernat; González-Martín, María Luisa; Monjo, Marta; Ramis, Joana M

    2016-05-11

    Myo-inositol hexaphosphate, also called phytic acid or phytate (IP6), is a natural molecule abundant in vegetable seeds and legumes. Among other functions, IP6 inhibits bone resorption. It is adsorbed on the surface of hydroxyapatite, inhibiting its dissolution and decreasing the progressive loss of bone mass. We present here a method to directly functionalize Ti surfaces covalently with IP6, without using a cross-linker molecule, through the reaction of the phosphate groups of IP6 with the TiO2 layer of Ti substrates. The grafting reaction consisted of an immersion in an IP6 solution to allow the physisorption of the molecules onto the substrate, followed by a heating step to obtain its chemisorption, in an adaptation of the T-Bag method. The reaction was highly dependent on the IP6 solution pH, only achieving a covalent Ti-O-P bond at pH 0. We evaluated two acidic pretreatments of the Ti surface, to increase its hydroxylic content, HNO3 30% and HF 0.2%. The structure of the coated surfaces was characterized by X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and ellipsometry. The stability of the IP6 coating after three months of storage and after sterilization with γ-irradiation was also determined. Then, we evaluated the biological effect of Ti-IP6 surfaces in vitro on MC3T3-E1 osteoblastic cells, showing an osteogenic effect. Finally, the effect of the surfaces on the adhesion and biofilm viability of oral microorganisms S. mutans and S. sanguinis was also studied, and we found that Ti-IP6 surfaces decreased the adhesion of S. sanguinis. A surface that actively improves osseointegration while decreasing the bacterial adhesion could be suitable for use in bone implants.

  13. Initial Results of an Evidence-Based Safe Patient Handling and Mobility Program to Decrease Hospital Worker Injuries.

    PubMed

    Przybysz, Linda; Levin, Pamela F

    2017-02-01

    The rate for musculoskeletal injuries among health care workers is one of the highest for all industrial sectors in the United States; these injuries often occur during manual handling (i.e., lifting, moving, transferring, and repositioning) of patients. The following article describes the process used to complete a comprehensive assessment, as well as the planning, implementation, and initial evaluation of a quality improvement program to reduce work-related musculoskeletal disorders (WMSD) among health care workers employed by a rural Midwest hospital. Key elements for WMSD injury reduction were identified and compared across literature sources, national standards, and current state and federal legislative requirements for hospitals. The program used a multi-factor design that included evidence-based interventions (i.e., those supported by emerging evidence) to create a comprehensive Safe Patient Handling and Mobility (SPHM) program intended to address the unique needs of the organization. Initial program results are reviewed as well as significant considerations and challenges for SPHM programs.

  14. Increased Mobility of Major Histocompatibility Complex I-Peptide Complexes Decreases the Sensitivity of Antigen Recognition*S⃞

    PubMed Central

    Segura, Jean-Manuel; Guillaume, Philippe; Mark, Silke; Dojcinovic, Danijel; Johannsen, Alexandre; Bosshard, Giovanna; Angelov, Georgi; Legler, Daniel F.; Vogel, Horst; Luescher, Immanuel F.

    2008-01-01

    CD8+ cytotoxic T lymphocytes (CTL) can recognize and kill target cells expressing only a few cognate major histocompatibility complex (MHC) I-peptide complexes. This high sensitivity requires efficient scanning of a vast number of highly diverse MHC I-peptide complexes by the T cell receptor in the contact site of transient conjugates formed mainly by nonspecific interactions of ICAM-1 and LFA-1. Tracking of single H-2Kd molecules loaded with fluorescent peptides on target cells and nascent conjugates with CTL showed dynamic transitions between states of free diffusion and immobility. The immobilizations were explained by association of MHC I-peptide complexes with ICAM-1 and strongly increased their local concentration in cell adhesion sites and hence their scanning by T cell receptor. In nascent immunological synapses cognate complexes became immobile, whereas noncognate ones diffused out again. Interfering with this mobility modulation-based concentration and sorting of MHC I-peptide complexes strongly impaired the sensitivity of antigen recognition by CTL, demonstrating that it constitutes a new basic aspect of antigen presentation by MHC I molecules. PMID:18579518

  15. High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina

    PubMed Central

    Nawaz, Mohd Imtiaz; Siddiquei, Mohammad Mairaj; Al-Kharashi, Abdullah S.; Kangave, Dustan; Mohammad, Ghulam

    2013-01-01

    To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration. PMID:23766563

  16. Air, bone and soft tissue excitation of the cochlea in the presence of severe impediments to ossicle and window mobility.

    PubMed

    Perez, Ronen; Adelman, Cahtia; Chordekar, Shai; Ishai, Reuven; Sohmer, Haim

    2015-04-01

    Clinical conditions have been described in which one of the two cochlear windows is immobile (otosclerosis) or absent (round window atresia), but nevertheless bone conduction (BC) thresholds are relatively unaffected. To clarify this apparent paradox, experimental manipulations which would severely impede several of the classical osseous mechanisms of BC were induced in fat sand rats, including discontinuity or immobilization of the ossicular chain, coupled with window fixation. Effects of these manipulations were assessed by recording auditory nerve brainstem evoked response (ABR) thresholds to stimulation by air conduction (AC), by osseous BC and by non-osseous BC (also called soft tissue conduction-STC) in which the BC bone vibrator is applied to skin sites. Following the immobilization, discontinuity and window fixation, auditory stimulation was also delivered to cerebro-spinal fluid (CSF) and to saline applied to the middle ear cavity. While the manipulations (immobilization, discontinuity, window fixation) led to an elevation of AC thresholds, nevertheless, there was no change in osseous and non-osseous BC thresholds. On the other hand, ABR could be elicited in response to fluid pressure stimulation to CSF and middle ear saline, even in the presence of the severe restriction of ossicular chain and window mobility. The results of these experiments in which osseous and non-osseous BC thresholds remained unchanged in the presence of severe restriction of the classical middle ear mechanisms and in the absence of an efficient release window, while ABR could be recorded in response to fluid pressure auditory stimulation to fluid sites, indicate that it is possible that the inner ear may be activated at low sound intensities by fast fluid pressure stimulation. At higher sound intensities, a slower passive basilar membrane traveling wave may serve to excite the inner ear.

  17. The effect of Pilates based exercise on mobility, postural stability, and balance in order to decrease fall risk in older adults.

    PubMed

    Pata, Rachel W; Lord, Katrina; Lamb, Jamie

    2014-07-01

    Falls are a common problem in older adults. Impaired balance, mobility and postural stability are risk factors for falling. Limited research has been performed on Pilates exercise and the ability to decrease fall risk. In this quasi-experimental study, 35 adults (61-87 years old) participated in an 8-week Pilates based exercise program. Blind examiners conducted the Timed Up and Go (TUG), Forward Reach Test, and Turn 180 Test before and after the intervention. Number of falls, perception of Pilates, and fear of falling was also recorded. Thirty-two (91.4%) participants completed post-test measures. Significant improvements were seen in the TUG (p <0.001) and Turn 180 Test (p = 0.002). Improvements were also demonstrated in the Forward Reach Test (p = 0.049). A positive perception of the Pilates program and decreased fear of falling was shown. Results suggest a Pilates based exercise program may be effective in improving balance, mobility and postural stability to decrease fall risk. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair.

    PubMed

    Wang, Yigang; Haider, Husnain K; Ahmad, Nauman; Xu, Meifeng; Ge, Ruowen; Ashraf, Muhammad

    2006-05-01

    We postulated that combining cell based hVEGF165 gene delivery with cytokine-induced mobilization of bone marrow cells (BMC) may give better prognosis in an infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received 1 x 10(6) BMC from transgenic GFP+ male mice. One month later, acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (N = 12) to receive intramyocardial injections of 10 microl DMEM without cells (group 1; group 2) or with 1x10(5) mesenchymal stem cells (MSC) over-expressing hVEGF165 (group 3; group 4). The animals received either cytokine therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI. Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and cardiac tissue was harvested for immunohistological studies. We observed regeneration and extensive survival of BMC in and around the infarcted myocardium in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as compared with groups 1 and 2 in peri-infarct area. Fibrotic area was significantly reduced with improved LV-contractile function in group 2 and 4. LV-systolic and diastolic functions were well-preserved in group 4 as indicated by +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of MSC overexpressing VEGF combined with cytokine induced BMC mobilization is superior to either of the monotherapy approach for angiomyogenesis and LV-function recovery.

  19. Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer’s Disease

    PubMed Central

    Dengler-Crish, Christine M.; Smith, Matthew A.; Wilson, Gina N.

    2016-01-01

    Reduced bone mineral density (BMD) and its clinical sequelae, osteoporosis, occur at a much greater rate in patients with Alzheimer’s disease (AD), often emerging early in the disease before significant cognitive decline is seen. Reduced BMD translates to increased bone fracture risk, decreased quality of life, and increased mortality for AD patients. However, the mechanism responsible for this observation is unclear. We hypothesize that bone loss is an additional component of an AD prodrome-changes that emerge prior to dementia and are mediated by dysfunction of the central serotonergic pathways. We characterized the skeletal phenotype of htau mice that express human forms of the microtubule-associated protein tau that become pathologically hyperphosphorylated in AD. Using radiographic densitometry, we measured BMD in female and male htau mice from 2–6 months of age–time-points prior to the presence of significant tauopathy in the hippocampal/entorhinal regions characteristic of this model. We found a significantly reduced BMD phenotype in htau mice that was most pronounced in males. Using western blotting and immunofluorescence, we showed overall reduced tryptophan hydroxylase (TPH) protein in htau brainstem and a 70% reduction in TPH-positive cells in the dorsal raphe nucleus (DRN)–a pivotal structure in the regulation of the adult skeleton. Elevations of hyperphosphorylated tau (ptau) proteins were also measured in brainstem, and co-labeled immunofluorescence studies showed presence of ptau in TPH-positive cells of the DRN as early as 4 months of age in htau mice. Together, these findings demonstrate that reduced BMD occurs earlier than overt degeneration in a tau-based AD model and that pathological changes in tau phosphorylation occur in the serotonin-producing neurons of the brainstem raphe in these mice. This illuminates a need to define a mechanistic relationship between bone loss and serotonergic deficits in early AD. PMID:27814296

  20. Prophylactic vertebroplasty procedure applied with a resorbable bone cement can decrease the fracture risk of sandwich vertebrae: long-term evaluation of clinical outcomes

    PubMed Central

    Jia, Pu; Tang, Hai; Chen, Hao; Bao, Li; Feng, Fei; Yang, He; Li, Jinjun

    2017-01-01

    A sandwich vertebra is formed after multiple osteoporotic vertebral fractures treated by percutaneous vertebroplasty, which has a risk of developing new fractures. The purpose of our study was to (i) investigate the occurrence of new fractures in sandwich vertebra after cement augmentation procedures and to (ii) evaluate the clinical outcomes after prophylactic vertebral reinforcement applied with resorbable bone cement. From June 2011 to 2014, we analysed 55 patients with at least one sandwich vertebrae and treated with percutaneous vertebroplasty. Eighteen patients were treated by prophylactic vertebroplasty with a resorbable bone cement to strengthen the sandwich vertebrae as the prevention group. The others were the non-prevention group. All patients were examined by spinal radiographs within 1 day, 6 months, 12 months, 24 months and thereafter. The incidence of sandwich vertebra is 8.25% (55/667) in our study. Most sandwich vertebrae (69.01%, 49/71) are distributed in the thoracic–lumbar junction. There are 24 sandwich vertebrae (18 patients) and 47 sandwich vertebrae (37 patients) in either prevention group or non-prevention group, respectively. No significant difference is found between age, sex, body mass index, bone mineral density, cement disk leakage, sandwich vertebrae distribution or Cobb angle in the two groups. In the follow-up, 8 out of 37 (21.6%) patients (with eight sandwich vertebrae) developed new fractures in non-prevention’ group, whereas no new fractures were detected in the prevention group. Neither Cobb angle nor vertebral compression rate showed significant change in the prevention group during the follow-up. However, in the non-prevention group, we found that Cobb angle increased and vertebral height lost significantly (P < 0.05). Prophylactic vertebroplasty procedure applied with resorbable bone cement could decrease the rate of new fractures of sandwich vertebrae. PMID:28149529

  1. Bone marrow AT1 augments neointima formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1{alpha}.

    PubMed

    Yokoi, Hirokazu; Yamada, Hiroyuki; Tsubakimoto, Yoshinori; Takata, Hiroki; Kawahito, Hiroyuki; Kishida, Sou; Kato, Taku; Matsui, Akihiro; Hirai, Hideyo; Ashihara, Eishi; Maekawa, Taira; Iwai, Masaru; Horiuchi, Masatsugu; Ikeda, Kouji; Takahashi, Tomosaburo; Okigaki, Mitsuhiko; Matsubara, Hiroaki

    2010-01-01

    Bone marrow (BM)-derived endothelial progenitor cells (EPCs) and vascular smooth muscle progenitor cells (VPCs) contribute to neointima formation, whereas the angiotensin II (Ang II) type 1 receptor (AT(1))-mediated action on BM-derived progenitors remains undefined. A wire-induced vascular injury was performed in the femoral artery of BM-chimeric mice whose BM was repopulated with AT(1)-deficient (BM-Agtr1(-/-)) or wild-type (BM-Agtr1(+/+)) cells. Neointima formation was profoundly reduced by 38% in BM-Agtr1(-/-) mice. Although the number of circulating EPCs (Sca-1(+)Flk-1(+)) and extent of reendothelialization did not differ between the 2 groups, the numbers of both circulating VPCs (c-Kit(-)Sca-1(+)Lin(-)) and tissue VPCs (Sca-1(+)CD31(-)) incorporated into neointima were markedly decreased in BM-Agtr1(-/-) mice. The accumulation of aggregated platelets and their content of stromal cell-derived factor-1alpha (SDF-1alpha) were significantly reduced in BM-Agtr1(-/-) mice, accompanied by a decrease in the serum level of SDF-1alpha. Thrombin-induced platelets aggregation was dose-dependently inhibited (45% at 0.1 IU/mL, P<0.05) in Agtr1(-/-) platelets compared with Agtr1(+/+) platelets, accompanied by the reduced expression and release of SDF-1alpha. The BM-AT(1) receptor promotes neointima formation by regulating the mobilization and homing of BM-derived VPCs in a platelet-derived SDF-1alpha-dependent manner without affecting EPC-mediated reendothelialization.

  2. Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation.

    PubMed

    Meo, Anna; Ruggeri, Annalisa; La Rosa, Maria A; Zanghì, Laura; Morabito, Nancy; Duca, Lorena

    2006-01-01

    In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.

  3. The relationship of severe health disorders with bone loss, grip strength, and mobility in postmenopausal women - a 15-year follow-up study.

    PubMed

    Suuronen, Juha; Sjöblom, Samu; Honkanen, Risto; Koivumaa-Honkanen, Heli; Kröger, Heikki; Sirola, Joonas; Rikkonen, Toni

    2016-07-01

    To investigate the relationships of severe health disorders (SHD) with bone loss, grip strength (GS) and mobility in postmenopausal women. The study sample consisted of 2227 Finnish women (mean age 53.2) from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) cohort. Postal inquiries and clinical measurements were completed during the 15-year follow-up at 5-year intervals between 1989 and 2004. Femoral neck bone mineral density (BMD) and GS were measured. Life-style factors and mobility were obtained via postal inquiries. Work disability pension according to the ICD-9 was an indicator of a SHD. At the baseline 242 women had SHD, 506 got late SHD during 1989-1995, whereas 1479 women had none until 1996. The women with baseline SHD had higher annual bone loss (0.44%) than those without SHD (0.34%) (p < 0.05), those with late SHD (0.39%) no difference was seen. Bone loss was highest with respiratory diseases, but BMD was lowest throughout the follow-up in nervous and sense organ diseases. Lower GS and mobility was also associated with SHD. Effects of SHDs on BMD, GS, and mobility are disease-specific. Thus, rehabilitation should be encouraged in postmenopausal women with SHD, especially in case of diseases of respiratory and nervous system. Implications for Rehabilitation Osteoporosis, muscle strength and co-morbidity Women with severe health disorders (SHD) leading to work disability have impaired musculoskeletal health. Active monitoring of the musculoskeletal health is advised for those with SHD. Women with SHD may benefit from rehabilitative treatment in order to avoid complications of musculoskeletal impairments.

  4. Supplementary biotin decreases tibial bone weight, density and strength in riboflavin-deficient starter diets for turkey poults.

    PubMed

    Hocking, P M; Stevenson, E; Beard, P M

    2013-01-01

    1. Growth and skeletal responses to different dietary concentrations of riboflavin and biotin were compared in turkey poults from hatch to 21 d of age. The birds were fed on a turkey starter diet with different concentrations of supplementary riboflavin (0, 20 and 40 mg/kg) and biotin (0, 0.3 and 0.6 mg/kg) in a factorial design. 2. Poults fed on diets with no supplementary riboflavin had poor gait scores, decreased times to sit and higher rates of culling compared to poults fed on the control diet (20 mg riboflavin and 0.3 mg biotin/kg [corrected] diet). Histologically, riboflavin deficiency was associated with a peripheral neuropathy similar to that described previously in chicks and, unexpectedly, in growth plate abnormalities. 3. Tibiae of poults fed on the control diet were larger, more dense, stronger and stiffer than the diets with no supplementary riboflavin. 4. Increasing supplementary biotin in poults fed on diets with no supplementary riboflavin was associated with a decrease in tibia weight, density, strength and stiffness. 5. The results demonstrated that riboflavin deficiency in fast-growing turkey poults was associated with growth retardation, growth plate disturbance and peripheral nerve dysfunction leading to an inability to walk.

  5. Limited change in dune mobility in response to a large decrease in wind power in semi-arid northern China since the 1970s

    USGS Publications Warehouse

    Mason, J.A.; Swinehart, J.B.; Lu, H.; Miao, X.; Cha, P.; Zhou, Y.

    2008-01-01

    The climatic controls on dune mobility, especially the relative importance of wind strength, remain incompletely understood. This is a key research problem in semi-arid northern China, both for interpreting past dune activity as evidence of paleoclimate and for predicting future environmental change. Potential eolian sand transport, which is approximately proportional to wind power above the threshold for sand entrainment, has decreased across much of northern China since the 1970s. Over the same period, effective moisture (ratio of precipitation to potential evapotranspiration) has not changed significantly. This "natural experiment" provides insight on the relative importance of wind power as a control on dune mobility in three dunefields of northern China (Mu Us, Otindag, and Horqin), although poorly understood and potentially large effects of human land use complicate interpretation. Dune forms in these three regions are consistent with sand transport vectors inferred from weather station data, suggesting that wind directions have remained stable and the stations adequately represent winds that shaped the dunes. The predicted effect of weaker winds since the 1970s would be dune stabilization, with lower sand transport rates allowing vegetation cover to expand. Large portions of all three dunefields remained stabilized by vegetation in the 1970s despite high wind power. Since the 1970s, trends in remotely sensed vegetation greenness and change in mobile dune area inferred from sequential Landsat images do indicate widespread dune stabilization in the eastern Mu Us region. On the other hand, expansion of active dunes took place farther west in the Mu Us dunefield and especially in the central Otindag dunefield, with little overall change in two parts of the Horqin dunes. Better ground truth is needed to validate the remote sensing analyses, but results presented here place limits on the relative importance of wind strength as a control on dune mobility in the

  6. Fall-related self-efficacy, not balance and mobility performance, is related to accidental falls in chronic stroke survivors with low bone mineral density

    PubMed Central

    Pang, Marco Y.C.; Eng, Janice J.

    2011-01-01

    Introduction Chronic stroke survivors with low bone mineral density (BMD) are particularly prone to fragility fractures. The purpose of this study was to identify the determinants of balance, mobility and falls in this sub-group of stroke patients. Methods Thirty nine chronic stroke survivors with low hip BMD (T-score <-1.0) were studied. Each subject was evaluated for: balance, mobility, leg muscle strength, spasticity, and falls-related self-efficacy. Any falls in the past 12 months were also recorded. Multiple regression analysis was used to identify the determinants of balance and mobility performance whereas logistic regression was used to identify the determinants of falls. Results Multiple regression analysis revealed that after adjusting for basic demographics, falls-related self-efficacy remained independently associated with balance/mobility performance (R2=0.494, P<0.001). Logistic regression showed that falls-related self-efficacy, but not balance and mobility performance, was a significant determinant of falls (odds ratio: 0.18, P=0.04). Conclusions Falls-related self-efficacy, but not mobility and balance performance, was the most important determinant of accidental falls. This psychological factor should not be overlooked in the prevention of fragility fractures among chronic stroke survivors with low hip BMD. PMID:18097709

  7. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells.

    PubMed

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2017-04-06

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration.

  8. Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress

    PubMed Central

    de Souza, Veruska Cintia Alexandrino; Pereira, Thiago Almeida; Teixeira, Valéria Wanderley; Carvalho, Helotonio; de Castro, Maria Carolina Accioly Brelaz; D’assunção, Carolline Guimarães; de Barros, Andréia Ferreira; Carvalho, Camila Lima; de Lorena, Virgínia Maria Barros; Costa, Vláudia Maria Assis; Teixeira, Álvaro Aguiar Coelho; Figueiredo, Regina Celia Bressan Queiroz; de Oliveira, Sheilla Andrade

    2017-01-01

    AIM To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage. METHODS Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay. RESULTS CD11b+CD14+ monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b+CD14+ monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin. CONCLUSION Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors. PMID:28811709

  9. Two-handed grip on a mobile phone affords greater thumb motor performance, decreased variability, and a more extended thumb posture than a one-handed grip.

    PubMed

    Trudeau, Matthieu B; Asakawa, Deanna S; Jindrich, Devin L; Dennerlein, Jack T

    2016-01-01

    Holding a mobile computing device with two hands may affect thumb motor performance, joint postures, and device stability compared to holding the device and tapping the touchscreen with the thumb of the holding hand. We tested the hypotheses that holding a touchscreen mobile phone with two hands lead to increased thumb motor performance, different thumb postures, and decreased device movement relative to using one hand. Ten right-handed participants completed reciprocal thumb tapping tasks between emulated keys on a smartphone in either a one- (portrait) or two-handed (landscape) grip configuration. Effective index of performance measured from Fitts' Law was 9% greater (p < 0.001), movement time 7% faster (p < 0.001), and taps were 4% more precise (p < 0.016) for the two-handed grip. Tapping with a two-handed grip involved significantly different wrist and thumb postures than a one-handed grip. Variability of the computing device's movement was 36-63% lower for the two-handed grip compared to the one-handed grip condition (p < 0.001). The support for our hypotheses suggests that a two-handed grip results in increased performance and more extended wrist and thumb postures than a single-handed grip. Device designs that allow two-handed grips may afford increased performance relative to a one-handed grip. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Intermittent Hypoxia Mobilizes Bone Marrow-Derived Very Small Embryonic-Like Stem Cells and Activates Developmental Transcriptional Programs in Mice

    PubMed Central

    Gharib, Sina A.; Dayyat, Ehab A.; Khalyfa, Abdelnaby; Kim, Jinkwan; Clair, Heather B.; Kucia, Magdalena; Gozal, David

    2010-01-01

    Background: Obstructive sleep apnea is a prevalent disorder associated with cognitive dysfunction and cardiovascular and metabolic morbidity and is characterized by recurrent episodes of hypoxia during sleep. Bone marrow-derived very small embryonic-like (VSEL) pluripotent stem cells represent a recruitable pool that may play an important role in organ repair after injury. We hypothesized that exposure to intermittent hypoxia (IH) can mobilize VSELs from the bone marrow (BM) to peripheral blood (PB) in mice and can activate distinct transcriptional programs. Methods: Adult mice were exposed to IH or normoxia for 48 hours. VSELs were sorted from BM and PB using flow cytometry. Plasma levels of stem cell chemokines, stromal cell derived factor-1 (SDF-1), hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) were measured. Transcriptional profiling of VSELs was performed, and differentially expressed genes were mapped to enriched functional categories and genetic networks. Results: Exposure to IH elicited migration of VSELs from BM to PB and elevations in plasma levels of chemokines. More than 1100 unique genes were differentially expressed in VSELs in response to IH. Gene Ontology and network analysis revealed the activation of organ-specific developmental programs among these genes. Conclusions: Exposure to IH mobilizes VSELs from the BM to PB and activates distinct transcriptional programs in VSELs that are enriched in developmental pathways, including central nervous system development and angiogenesis. Thus, VSELs may serve as a reserve mobile pool of pluripotent stem cells that can be recruited into PB and may play an important role in promoting end-organ repair during IH. Citation: Gharib SA; Dayyat EA; Khalyfa A; Kim J; Clair HB; Kucia M; Gozal D. Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem cells and activates developmental transcriptional programs in mice. SLEEP 2010;33(11):1439-1446. PMID:21102985

  11. Negative association of donor age with CD34⁺ cell dose in mixture allografts of G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood harvests.

    PubMed

    Li, Yan; Chang, Yingjun; Xu, Lanping; Zhang, Xiaohui; Huang, Xiaojun

    2014-01-01

    The effects of donor characteristics on CD34(+) cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) were used. The aim of this study was to investigate the effects of donor characteristics on CD34(+) cell dose in mixture allografts of G-BM and G-PB. A total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People's Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 µg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34(+) cell dose less than 2×10(6) cells/kg recipient body weight was considered a poor mobilization. Of the 162 donors, 31 (19.1%) did not attain this threshold. The obtained median CD34(+) cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×10(6)/kg, 2.40×10(6)/kg, and 3.47×10(6)/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34(+) cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index (BMI), and weight. Donor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34(+) cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34(+) cells for transplantation.

  12. G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow.

    PubMed

    Shimizu, Naomi; Nakaseko, Chiaki; Jiang, Meizi; Nishii, Keigo; Yokote, Koutaro; Iseki, Tohru; Higashi, Morihiro; Tamaru, Junichi; Schneider, Wolfgang Johann; Bujo, Hideaki

    2014-07-01

    Granulocyte colony-stimulating factor (G-CSF) induces the mobilization of leukocytes from the bone marrow (BM) to the circulation by a yet incompletely understood mechanism. Here, we describe that the membrane-bound receptor LR11 is highly expressed in human myeloid cells and that the shed soluble form of LR11 (sLR11) is a modifier of myeloid cell migration. In the process of leukocyte mobilization by G-CSF treatment, circulating sLR11 levels are transiently elevated in humans and mice. Moreover, following G-CSF treatment, the sLR11 levels in patients show significant positive correlation with the numbers of mobilized leukocytes. The changes of LR11 levels in BM cells and of sLR11 released into the BM fluid of mice correlate tightly with the changes in circulating sLR11 levels. G-CSF dose-dependently enhanced sLR11 release from HL-60 cells, which in turn accelerated cell migration. Finally, cooperatively with tumor necrosis factor-α (TNF-α) and G-CSF, sLR11 increased the attachment of floating cells (HL-60 and U937) to endothelial cells. We propose that sLR11 is a novel candidate modifier of G-CSF-mediated mobilization of hematologic cells. Identification of sLR11 as a regulatory component of G-CSF-mediated hematologic cell mobilization may facilitate further improvement of hematologic stem cell collection for clinical applications.

  13. tPA-MMP-9 Axis Plays a Pivotal Role in Mobilization of Endothelial Progenitor Cells from Bone Marrow to Circulation and Ischemic Region for Angiogenesis

    PubMed Central

    Day, Yuan-Ji

    2016-01-01

    We examined the role of tissue plasminogen activator- (tPA-) matrix metalloproteinase- (MMP-) 9 in mobilizing endothelial progenitor cells (EPCs) from bone marrow to circulation and critical limb ischemia (CLI) region. Male C57BL/6J mice having been irradiated were categorized into wild-type mice (WT) receiving WT bone marrow cell (BMC) transfusion (group 1), WT mice receiving MMP-9 knockout (MMP-9−/−) BMC (group 2), MMP-9−/− receiving MMP-9−/− BMC (group 3), and MMP-9−/− receiving WT BMC (group 4), each of which was subdivided into sham control (SC), CLI, SC-tPA, and CLI-tPA. In groups 1 and 4, by post-CLI 18 h and day 14, circulating EPC (C-kit+/CD31+, Sca-1+/KDR+) levels were highest in CLI-tPA subgroup. In groups 2 and 3, EPC levels did not differ among all subgroups. The EPC levels in bone marrow were higher in groups 2 and 3 than those in groups 1 and 4. By day 14, in animals with CLI, expression levels of proangiogenic factors (CXCR4, SDF-1α, and VEGF) showed similar trends as circulating EPC levels. Moreover, the number of infiltrated neutrophils and macrophages in quadriceps was higher in groups 1 and 4 than groups in 2 and 3. In conclusion, tPA-MMP-9 axis plays a crucial role in EPC mobilization and angiogenesis in experimental CLI. PMID:27610138

  14. Decreased expression of Fli-1 in bone marrow-derived haematopoietic cells significantly affects disease development in Murphy Roths Large/lymphoproliferation (MRL/lpr) mice.

    PubMed

    Molano, I; Mathenia, J; Ruiz, P; Gilkeson, G S; Zhang, X K

    2010-05-01

    The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Decreased expression of Fli-1 in heterozygous (Fli-1(+/-)) Murphy Roths Large (MRL)/lpr mice resulted in significantly lower kidney pathological scores and markedly increased survival. In this study, bone marrow (BM) transplantation was used to investigate the role of decreased expression of Fli-1 in haematopoietic versus non-haematopoietic cell lineages in autoimmune disease development. Wild-type (WT) MRL/lpr that received BM from Fli-1(+/-) MRL/lpr mice had statistically significantly lower autoantibodies, less proteinuria, reduced renal disease and prolonged survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Although not statistically significant, Fli-1(+/-) MRL/lpr mice that received BM from WT MRL/lpr mice also had lower autoantibodies and improved survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Our data indicate that expression of Fli-1 in haematopoietic cell lineages has a significant effect on disease development in MRL/lpr mice.

  15. Decreased expression of Fli-1 in bone marrow-derived haematopoietic cells significantly affects disease development in Murphy Roths Large/lymphoproliferation (MRL/lpr) mice

    PubMed Central

    Molano, I; Mathenia, J; Ruiz, P; Gilkeson, G S; Zhang, X K

    2010-01-01

    The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Decreased expression of Fli-1 in heterozygous (Fli-1+/−) Murphy Roths Large (MRL)/lpr mice resulted in significantly lower kidney pathological scores and markedly increased survival. In this study, bone marrow (BM) transplantation was used to investigate the role of decreased expression of Fli-1 in haematopoietic versus non-haematopoietic cell lineages in autoimmune disease development. Wild-type (WT) MRL/lpr that received BM from Fli-1+/− MRL/lpr mice had statistically significantly lower autoantibodies, less proteinuria, reduced renal disease and prolonged survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Although not statistically significant, Fli-1+/− MRL/lpr mice that received BM from WT MRL/lpr mice also had lower autoantibodies and improved survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Our data indicate that expression of Fli-1 in haematopoietic cell lineages has a significant effect on disease development in MRL/lpr mice. PMID:20015093

  16. Emergency department crowding is associated with decreased quality of analgesia delivery for children with pain related to acute, isolated, long-bone fractures.

    PubMed

    Sills, Marion R; Fairclough, Diane L; Ranade, Daksha; Mitchell, Michael S; Kahn, Michael G

    2011-12-01

    The authors sought to determine which quality measures of analgesia delivery are most influenced by emergency department (ED) crowding for pediatric patients with long-bone fractures. This cross-sectional, retrospective study included patients 0-21 years seen for acute, isolated long-bone fractures, November 2007 to October 2008, at a children's hospital ED. Nine quality measures were studied: six were based on the timeliness (1-hour receipt) and effectiveness (receipt/nonreceipt) of three fracture-related processes: pain score, any analgesic, and opioid analgesic administration. Three equity measures were also tested: language, identified primary care provider (PCP), and insurance. The primary independent variable was a crowding measure: ED occupancy. Models were adjusted for age, language, insurance, identified PCP, triage level, ambulance arrival, and time of day. The adjusted risk of each timeliness or effectiveness quality measure was measured at five percentiles of crowding and compared to the risk at the 10th and 90th percentiles. The role of equity measures as moderators of the crowding-quality models was tested. The study population included 1,229 patients. Timeliness and effectiveness quality measures showed an inverse association with crowding-an effect not moderated by equity measures. Patients were 4% to 47% less likely to receive timely care and were 3% to 17% less likely to receive effective care when each crowding measure was at the 90th than at the 10th percentile (p < 0.05). For three of the six quality measures, quality declined steeply between the 75th and 90th crowding percentiles. Crowding is associated with decreased timeliness and effectiveness, but not equity, of analgesia delivery for children with fracture-related pain. © 2011 by the Society for Academic Emergency Medicine.

  17. Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow-Derived Mesenchymal Stem Cells.

    PubMed

    Kalomoiris, Stefanos; Cicchetto, Andrew C; Lakatos, Kinga; Nolta, Jan A; Fierro, Fernando A

    2016-09-01

    Mesenchymal stem cells (MSCs) are an excellent source for numerous cellular therapies due to their simple isolation, low immunogenicity, multipotent differentiation potential and regenerative secretion profile. However, over-expanded MSCs show decreased therapeutic efficacy. This shortcoming may be circumvented by identifying methods that promote self-renewal of MSCs in culture. HMGA2 is a DNA-binding protein that regulates self-renewal in multiple types of stem cells through chromatin remodeling, but its impact on human bone marrow-derived MSCs is not known. Using an isolation method to obtain pure MSCs within 9 days in culture, we show that expression of HMGA2 quickly decreases during early expansion of MSCs, while let-7 microRNAs (which repress HMGA2) are simultaneously increased. Remarkably, we demonstrate that FGF-2, a growth factor commonly used to promote self-renewal in MSCs, rapidly induces HMGA2 expression in a time- and concentration-dependent manner. The signaling pathway involves FGF-2 receptor 1 (FGFR1) and ERK1/2, but acts independent from let-7. By silencing HMGA2 using shRNAs, we demonstrate that HMGA2 is necessary for MSC proliferation. However, we also show that over-expression of HMGA2 does not increase cell proliferation, but rather abrogates the mitogenic effect of FGF-2, possibly through inhibition of FGFR1. In addition, using different methods to assess in vitro differentiation, we show that modulation of HMGA2 inhibits adipogenesis, but does not affect osteogenesis of MSCs. Altogether, our results show that HMGA2 expression is associated with highly proliferating MSCs, is tightly regulated by FGF-2, and is involved in both proliferation and adipogenesis of MSCs. J. Cell. Biochem. 117: 2128-2137, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow-Derived Mesenchymal Stem Cells

    PubMed Central

    Kalomoiris, Stefanos; Cicchetto, Andrew C.; Lakatos, Kinga; Nolta, Jan A.; Fierro, Fernando A.

    2017-01-01

    Mesenchymal stem cells (MSCs) are an excellent source for numerous cellular therapies due to their simple isolation, low immunogenicity, multipotent differentiation potential and regenerative secretion profile. However, over-expanded MSCs show decreased therapeutic efficacy. This shortcoming may be circumvented by identifying methods that promote self-renewal of MSCs in culture. HMGA2 is a DNA-binding protein that regulates self-renewal in multiple types of stem cells through chromatin remodeling, but its impact on human bone marrow-derived MSCs is not known. Using an isolation method to obtain pure MSCs within 9 days in culture, we show that expression of HMGA2 quickly decreases during early expansion of MSCs, while let-7 microRNAs (which repress HMGA2) are simultaneously increased. Remarkably, we demonstrate that FGF-2, a growth factor commonly used to promote self-renewal in MSCs, rapidly induces HMGA2 expression in a time-and concentration-dependent manner. The signaling pathway involves FGF-2 receptor 1 (FGFR1) and ERK1/2, but acts independent from let-7. By silencing HMGA2 using shRNAs, we demonstrate that HMGA2 is necessary for MSC proliferation. However, we also show that over-expression of HMGA2 does not increase cell proliferation, but rather abrogates the mitogenic effect of FGF-2, possibly through inhibition of FGFR1. In addition, using different methods to assess in vitro differentiation, we show that modulation of HMGA2 inhibits adipogenesis, but does not affect osteogenesis of MSCs. Altogether, our results show that HMGA2 expression is associated with highly proliferating MSCs, is tightly regulated by FGF-2, and is involved in both proliferation and adipogenesis of MSCs. PMID:26888666

  19. Compromised bone strength index in the hemiparetic distal tibia epiphysis among chronic stroke patients: the association with cardiovascular function, muscle atrophy, mobility, and spasticity

    PubMed Central

    Pang, Marco Y.C.; Ashe, Maureen C.; Eng, Janice J.

    2011-01-01

    Purpose To identify the determinants of the bone strength index (BSI) at the distal tibia in chronic stroke patients. Methods Sixty-three chronic stroke survivors underwent scanning of the distal tibia at the 4% site on both sides using peripheral quantitative computed tomography. The primary outcomes were trabecular bone mineral density (BMD) (mg/cm3), total BMD (mg/cm3), total bone area (mm2), and BSI (g2/cm4). Cardiovascular fitness, leg lean mass, gait velocity, and spasticity were also measured. Results Scans from 45 subjects were deemed to have acceptable quality and were included for subsequent analysis. The paretic side had significantly lower trabecular BMD, total BMD, and BSI than the non-paretic side (p<0.05). However, the total bone area demonstrated no significant side-to-side difference (p>0.05). After adjusting for relevant biological factors, peakoxygen consumption, leg muscle mass, gait velocity remained positively associated with tibial BSI on both sides (R2 change=6.9–14.2%), whereas spasticity of the paretic leg was negatively associated with tibial BSI on the same side (R2 change=4.8%). Conclusions Cardiovascular function, muscle atrophy, mobility, and spasticity are independently associated with BSI of the distal tibia epiphysis among chronic stroke patients. PMID:19882095

  20. G-CSF-mobilized Bone Marrow Mesenchymal Stem Cells Replenish Neural Lineages in Alzheimer's Disease Mice via CXCR4/SDF-1 Chemotaxis.

    PubMed

    Wu, Cheng-Chun; Wang, I-Fang; Chiang, Po-Min; Wang, Liang-Chao; Shen, Che-Kun James; Tsai, Kuen-Jer

    2016-10-05

    Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer's disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells. Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate into the brain, but only BM-MSCs replenished the neural lineage cells and contributed to neurogenesis in the brains of AD mice. Together, our data show that mobilized BM-MSCs are involved in the replenishment of neural lineages following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the potential use of BM-MSCs for further autogenically therapeutic applications.

  1. The Influence of Electromagnetic Radiation Generated by a Mobile Phone on the Skeletal System of Rats

    PubMed Central

    Sieroń-Stołtny, Karolina; Teister, Łukasz; Cieślar, Grzegorz; Sieroń, Dominik; Śliwinski, Zbigniew; Sieroń, Aleksander

    2015-01-01

    The study was focused on the influence of electromagnetic field generated by mobile phone on the skeletal system of rats, assessed by measuring the macrometric parameters of bones, mechanical properties of long bones, calcium and phosphorus content in bones, and the concentration of osteogenesis (osteocalcin) and bone resorption (NTX, pyridinoline) markers in blood serum. The study was carried out on male rats divided into two groups: experimental group subjected to 28-day cycle of exposures in electromagnetic field of 900 MHz frequency generated by mobile phone and a control, sham-exposed one. The mobile phone-generated electromagnetic field did not influence the macrometric parameters of long bones and L4 vertebra, it altered mechanical properties of bones (stress and energy at maximum bending force, stress at fracture), it decreased the content of calcium in long bones and L4 vertebra, and it altered the concentration of osteogenesis and bone resorption markers in rats. On the basis of obtained results, it was concluded that electromagnetic field generated by 900 MHz mobile phone does not have a direct impact on macrometric parameters of bones; however, it alters the processes of bone mineralization and the intensity of bone turnover processes and thus influences the mechanical strength of bones. PMID:25705697

  2. The influence of electromagnetic radiation generated by a mobile phone on the skeletal system of rats.

    PubMed

    Sieroń-Stołtny, Karolina; Teister, Łukasz; Cieślar, Grzegorz; Sieroń, Dominik; Śliwinski, Zbigniew; Kucharzewski, Marek; Sieroń, Aleksander

    2015-01-01

    The study was focused on the influence of electromagnetic field generated by mobile phone on the skeletal system of rats, assessed by measuring the macrometric parameters of bones, mechanical properties of long bones, calcium and phosphorus content in bones, and the concentration of osteogenesis (osteocalcin) and bone resorption (NTX, pyridinoline) markers in blood serum. The study was carried out on male rats divided into two groups: experimental group subjected to 28-day cycle of exposures in electromagnetic field of 900 MHz frequency generated by mobile phone and a control, sham-exposed one. The mobile phone-generated electromagnetic field did not influence the macrometric parameters of long bones and L4 vertebra, it altered mechanical properties of bones (stress and energy at maximum bending force, stress at fracture), it decreased the content of calcium in long bones and L4 vertebra, and it altered the concentration of osteogenesis and bone resorption markers in rats. On the basis of obtained results, it was concluded that electromagnetic field generated by 900 MHz mobile phone does not have a direct impact on macrometric parameters of bones; however, it alters the processes of bone mineralization and the intensity of bone turnover processes and thus influences the mechanical strength of bones.

  3. Bone cement

    PubMed Central

    Vaishya, Raju; Chauhan, Mayank; Vaish, Abhishek

    2013-01-01

    The knowledge about the bone cement is of paramount importance to all Orthopaedic surgeons. Although the bone cement had been the gold standard in the field of joint replacement surgery, its use has somewhat decreased because of the advent of press-fit implants which encourages bone in growth. The shortcomings, side effects and toxicity of the bone cement are being addressed recently. More research is needed and continues in the field of nanoparticle additives, enhanced bone–cement interface etc. PMID:26403875

  4. Flaxseed flour (Linum usitatissinum) consumption improves bone quality and decreases the adipocyte area of lactating rats in the post-weaning period.

    PubMed

    Ribeiro, Danielle Cavalcante; Pereira, Aline D'Avila; da Silva, Paula Cristina Alves; dos Santos, Aline de Sousa; de Santana, Fernanda Carvalho; Boueri, Bianca Ferolla da Camara; Pessanha, Carolina Ribeiro; de Abreu, Maíra Duque Coutinho; Mancini-Filho, Jorge; da Silva, Eduardo Moreira; do Nascimento-Saba, Celly Cristina Alves; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2016-01-01

    The aim of this work was to evaluate the effects of flaxseed flour in the intake on adiposity and femur structure of the lactating rats during the post-weaning period. After weaning, the lactating rats were divided into control (C, n = 6) and experimental (F, n = 6) groups treated with a diet containing flaxseed flour. Serum hormone and fatty acids composition, morphology of intra-abdominal adipocytes, computed tomography and biomechanical analyses of femur were determined. Food intake, body mass and hormone analysis have shown similar results. The F group showed the following (p < 0.05): lower arachidonic acid (-60%), total polyunsaturated fatty acids (-30%) and retroperitoneal adipocytes (-36%) area. Higher radiodensity of femoral head region (+29%) and higher maximum force (+18%), breaking strength (+18%) and rigidity (+31%). Fatty acid composition of flaxseed flour decreased the area of adipocytes and improved the bone quality, which may be associated with lower serum levels of arachidonic acid levels, during the post-weaning period.

  5. Decreased Body Mass Index in Schoolchildren After Yearlong Information Sessions With Parents Reinforced With Web and Mobile Phone Resources: Community Trial.

    PubMed

    Vilchis-Gil, Jenny; Klünder-Klünder, Miguel; Duque, Ximena; Flores-Huerta, Samuel

    2016-06-24

    The obesity pandemic has now reached children, and households should change their lifestyles to prevent it. The objective was to assess the effect of a comprehensive intervention on body mass index z-score (BMIZ) in schoolchildren. A yearlong study was conducted at 4 elementary schools in Mexico City. Intervention group (IG) and control group (CG) were split equally between governmental and private schools. Three educational in-person parents and children sessions were held at 2-month intervals to promote healthy eating habits and exercise. To reinforce the information, a website provided extensive discussion on a new topic every 2 weeks, including school snack menus and tools to calculate body mass index in children and adults. Text messages were sent to parents' mobile phones reinforcing the information provided. The IG contained 226 children and CG 181 children. We measured their weight and height and calculated BMIZ at 0, 6, and 12 months. The CG children showed a change of +0.06 (95% CI 0.01, 0.11) and +0.05 (95% CI 0.01, 0.10) in their BMIZ at 6 and 12 months, respectively. The BMIZ of IG children decreased by -0.13 (95% CI -0.19 to -0.06) and -0.10 (95% CI -0.16 to -0.03), respectively, and the effect was greater in children with obesity. The comprehensive intervention tested had beneficial effects, preserved the BMIZ of normal weight children, and reduced the BMIZ of children with obesity.

  6. Cloning of human Ca2+ homoeostasis endoplasmic reticulum protein (CHERP): regulated expression of antisense cDNA depletes CHERP, inhibits intracellular Ca2+ mobilization and decreases cell proliferation.

    PubMed Central

    Laplante, J M; O'Rourke, F; Lu, X; Fein, A; Olsen, A; Feinstein, M B

    2000-01-01

    A monoclonal antibody which blocks InsP(3)-induced Ca(2+) release from isolated endoplasmic reticulum was used to isolate a novel 4.0 kb cDNA from a human erythroleukaemia (HEL) cell cDNA expression library. A corresponding mRNA transcript of approx. 4.2 kb was present in all human cell lines and tissues examined, but cardiac and skeletal muscle had an additional transcript of 6.4 kb. The identification in GenBank(R) of homologous expressed sequence tags from many tissues and organisms suggests that the gene is ubiquitously expressed in higher eukaryotes. The gene was mapped to human chromosome 19p13.1. The cDNA predicts a 100 kDa protein, designated Ca(2+) homoeostasis endoplasmic reticulum protein (CHERP), with two putative transmembrane domains, multiple consensus phosphorylation sites, a polyglutamine tract of 12 repeats and regions of imperfect tryptophan and histadine octa- and nona-peptide repeats. In vitro translation of the full-length cDNA produced proteins of M(r) 128000 and 100000, corresponding to protein bands detected by Western blotting of many cell types. CHERP was co-localized in HEL cells with the InsP(3) receptor by two-colour immunofluorescence. Transfection of HEL cells with antisense cDNA led to an 80% decline in CHERP within 5 days of antisense induction, with markedly decreased intracellular Ca(2+) mobilization by thrombin, decreased DNA synthesis and growth arrest, indicating that the protein has an important function in Ca(2+) homoeostasis, growth and proliferation. PMID:10794731

  7. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy

    PubMed Central

    Navitskaya, Svetlana; O’Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B.; Busik, Julia V.

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy. PMID:26760976

  8. Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

    PubMed

    Chakravarthy, Harshini; Beli, Eleni; Navitskaya, Svetlana; O'Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B; Busik, Julia V

    2016-01-01

    Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

  9. P-glycoprotein overexpression in bone marrow-derived multipotent stromal cells decreases the risk of steroid-induced osteonecrosis in the femoral head.

    PubMed

    Han, Ning; Li, Zengchun; Cai, Zhengdong; Yan, Zuoqin; Hua, Yingqi; Xu, Chong

    2016-11-01

    P-glycoprotein (P-gp) plays a role in steroid-induced osteonecrosis of the femoral head (ONFH), but the underlying mechanism remains unknown. We hypothesized that P-gp overexpression can prevent ONFH by regulating bone marrow-derived multipotent stromal cell (BMSC) adipogenesis and osteogenesis. BMSCs from Sprague-Dawley rats were transfected with green fluorescent protein (GFP) or the multidrug resistance gene 1 (MDR1) encoding GFP and P-gp. Dexamethasone was used to induce BMSC differentiation. Adipogenesis was determined by measuring peroxisome proliferator-activated receptor (PPAR-γ) expression and the triglyceride level. Osteogenesis was determined by measuring runt-related transcription factor 2 (Runx2) expression and alkaline phosphatase activity. For in vivo experiments, rats were injected with saline, BMSCs expressing GFP (GFP-BMSCs) or BMSCs expressing GFP-P-gp (MDR1-GFP-BMSCs). After dexamethasone induction, adipogenesis was determined by measuring PPAR-γ expression and fatty marrow, whereas osteogenesis was detected by measuring Runx2 expression, trabecular parameters and the mineral apposition rate, followed by evaluation of the incidence of ONFH. Overexpression of P-gp in BMSCs resulted in markedly decreased expression of adipogenic markers and increased expression of osteogenic markers. Compared with rats injected with saline, rats injected with GFP-BMSCs showed reduced ONFH, and the injected GFP-positive BMSCs attached to trabecular surfaces and exhibited an osteoblast-like morphology. Compared with the rats injected with BMSCs expressing GFP alone, rats injected with BMSCs overexpressing GFP and P-gp showed lower adipocytic variables, higher osteogenic variables and lower incidence of ONFH. Overexpression of P-gp inhibited BMSC adipogenesis and promoted osteogenesis, which reduced the incidence of steroid-induced ONFH. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular

  10. Decreased Body Mass Index in Schoolchildren After Yearlong Information Sessions With Parents Reinforced With Web and Mobile Phone Resources: Community Trial

    PubMed Central

    Vilchis-Gil, Jenny; Klünder-Klünder, Miguel; Duque, Ximena

    2016-01-01

    Background The obesity pandemic has now reached children, and households should change their lifestyles to prevent it. Objective The objective was to assess the effect of a comprehensive intervention on body mass index z-score (BMIZ) in schoolchildren. Methods A yearlong study was conducted at 4 elementary schools in Mexico City. Intervention group (IG) and control group (CG) were split equally between governmental and private schools. Three educational in-person parents and children sessions were held at 2-month intervals to promote healthy eating habits and exercise. To reinforce the information, a website provided extensive discussion on a new topic every 2 weeks, including school snack menus and tools to calculate body mass index in children and adults. Text messages were sent to parents’ mobile phones reinforcing the information provided. The IG contained 226 children and CG 181 children. We measured their weight and height and calculated BMIZ at 0, 6, and 12 months. Results The CG children showed a change of +0.06 (95% CI 0.01, 0.11) and +0.05 (95% CI 0.01, 0.10) in their BMIZ at 6 and 12 months, respectively. The BMIZ of IG children decreased by -0.13 (95% CI -0.19 to -0.06) and -0.10 (95% CI -0.16 to -0.03), respectively, and the effect was greater in children with obesity. Conclusions The comprehensive intervention tested had beneficial effects, preserved the BMIZ of normal weight children, and reduced the BMIZ of children with obesity. PMID:27342650

  11. Adoptive transfer of bone marrow-derived dendritic cells decreases inhibitory and regulatory T-cell differentiation and improves survival in murine polymicrobial sepsis.

    PubMed

    Wang, Hong-Wei; Yang, Wen; Gao, Lei; Kang, Jia-Rui; Qin, Jia-Jian; Liu, Yue-Ping; Lu, Jiang-Yang

    2015-05-01

    A decrease in the number of dendritic cells (DCs) is a major cause of post-sepsis immunosuppression and opportunistic infection and is closely associated with poor prognosis. Increasing the number of DCs to replenish their numbers post sepsis can improve the condition. This therapeutic approach could improve recovery after sepsis. Eighty C57BL/6 mice were subjected to sham or caecal ligation and puncture (CLP) surgery. Mice were divided into four groups: (i) Sham + vehicle, (ii) Sham + DC, (iii) CLP + vehicle, and (iv) CLP + DC. Bone-marrow-derived DCs (BMDCs) were administered at 6, 12 and 24 hr after surgery. After 3 days, we assessed serum indices of organ function (alanine aminotransferase, aspartate aminotransferase, creatinine, amylase and lipase), organ tissue histopathology (haematoxylin and eosin staining), cytokine [interferon-γ (IFN-γ), tumour necrosis factor-α, interleukin-12p70 (IL-12p70), IL-6 and IL-10] levels in the serum, programmed death-1 (PD-1) expression on T cells, regulatory T-cell differentiation in the spleen, and the survival rate (monitored for 7 days). BMDC transfer resulted in the following changes: a significant reduction in damage to the liver, kidney and pancreas in the CLP-septic mice as well as in the pathological changes seen in the liver, lung, small intestine and pancreas; significantly elevated levels of the T helper type 1 (Th1) cytokines IFN-γ and IL-12p70 in the serum; decreased levels of the Th2 cytokines IL-6 and IL-10 in the serum; reduced expression of PD-1 molecules on CD4(+) T cells; reduced the proliferation and differentiation of splenic suppressor T cells and CD4(+)  CD25(+)  Foxp3(+) regulatory T cells, and a significant increase in the survival rate of the septic animals. These results show that administration of BMDCs may have modulated the differentiation and immune function of T cells and contributed to alleviate immunosuppression, hence reducing organ damage and mortality post sepsis. Hence

  12. Hematopoietic progenitor cells (HPC) from mobilized peripheral blood display enhanced migration and marrow homing compared to steady-state bone marrow HPC.

    PubMed

    Bonig, Halvard; Priestley, Gregory V; Oehler, Vivian; Papayannopoulou, Thalia

    2007-02-01

    Faster engraftment of G-CSF-mobilized peripheral blood (MPB) transplants compared to steady-state bone marrow (ssBM) is well documented and clinically relevant. A number of different factors likely contribute to this outcome. In the present study we explored whether independent of cell number there are intrinsic differences in the efficiency of progenitor cell homing to marrow between MPB and ssBM. Mobilization was achieved by continuous infusion of G-CSF alone or in combination with other mobilizing agents. In vivo homing assays, in vitro migration assays, gene expression analysis, and flow cytometry were utilized to compare homing-related in vivo and in vitro properties of MPB and ssBM HPC. Marrow homing of murine MPB HPC, generated by different mobilizing schemes, was reproducibly significantly superior to that of ssBM, in lethally irradiated as well as in nonirradiated hosts. This phenotype was independent of MMP9, selectins, and beta2- and alpha4-integrins. Superior homing was also observed for human MPB HPC transplanted into NOD/SCIDbeta2microglobulin(-/-) recipients. Inhibition of HPC migration abrogated the homing advantage of MPB but did not affect homing of ssBM HPC, whereas enhancement of motility by CD26 inhibition improved marrow homing only of ssBM HPC. Enhanced SDF-1-dependent chemotaxis and low CD26 expression on MPB HPC were identified as potential contributing factors. Significant contributions of the putative alternative SDF-1 receptor, RDC1, were unlikely based on gene expression data. The data suggest increased motility as a converging endpoint of complex changes seen in MPB HPC which is likely responsible for their favorable homing.

  13. Improved Mobilization of the CD34+ and CD133+ Bone Marrow-Derived Circulating Progenitor Cells by Freshly Isolated Intracoronary Bone Marrow Cell Transplantation in Patients with Ischemic Heart Disease

    PubMed Central

    Bozdag-Turan, Ilkay; Ortak, Jasmin; Akin, Ibrahim; Kische, Stephan; Schneider, Henrik; Turan, Cem Hakan; Rehders, Tim Christopher; Rauchhaus, Mathias; Kleinfeldt, Tilo; Adolph, Ester; Brehm, Micheal; Yokus, Sedat; Steiner, Stephan; Sahin, Kurtulus; Nienaber, Christoph A.; Ince, Hüseyin

    2011-01-01

    Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45+ and CD133/45+ CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45+ and CD133/45+ BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD. PMID:21190450

  14. Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight

    NASA Technical Reports Server (NTRS)

    Bloomberg, Jacob J.; Reschke, Millard F.; Clement, Gilles R.; Mulavara, Ajitkumar P.; Taylor, Laura C..

    2015-01-01

    Control of vehicles and other complex systems is a high-level integrative function of the central nervous system (CNS). It requires well-functioning subsystem performance, including good visual acuity, eye-hand coordination, spatial and geographic orientation perception, and cognitive function. Evidence from space flight research demonstrates that the function of each of these subsystems is altered by removing gravity, a fundamental orientation reference, which is sensed by vestibular, proprioceptive, and haptic receptors and used by the CNS for spatial orientation, posture, navigation, and coordination of movements. The available evidence also shows that the degree of alteration of each subsystem depends on a number of crew- and mission-related factors. There is only limited operational evidence that these alterations cause functional impacts on mission-critical vehicle (or complex system) control capabilities. Furthermore, while much of the operational performance data collected during space flight has not been available for independent analysis, those that have been reviewed are somewhat equivocal owing to uncontrolled (and/or unmeasured) environmental and/or engineering factors. Whether this can be improved by further analysis of previously inaccessible operational data or by development of new operational research protocols remains to be seen. The true operational risks will be estimable only after we have filled the knowledge gaps and when we can accurately assess integrated performance in off-nominal operational settings (Paloski et al. 2008). Thus, our current understanding of the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight is limited primarily to extrapolation of scientific research findings, and, since there are limited ground-based analogs of the sensorimotor and vestibular changes associated with space flight, observation of their functional

  15. Gremlin-mediated decrease in bone morphogenetic protein signaling promotes aristolochic acid-induced epithelial-to-mesenchymal transition (EMT) in HK-2 cells.

    PubMed

    Li, Yi; Wang, Zihua; Wang, Shuai; Zhao, Jinghong; Zhang, Jingbo; Huang, Yunjian

    2012-07-16

    Ingestion of aristolochic acid (AA) is associated with the development of aristolochic acid nephropathy (AAN), which is characterized by progressive tubulointerstitial fibrosis, chronic renal failure and urothelial cancer. Our previous study showed that bone morphogenetic protein-7 (BMP-7) could attenuate AA-induced epithelial-to-mesenchymal transition (EMT) in human proximal tubule epithelial cells (PTEC). However, how gremlin (a BMP-7 antagonist) antagonizes the BMP-7 action in PTEC remained unsolved. The aim of the current study was to investigate the role of gremlin in AA-induced EMT in PTEC (HK-2 cells). HK-2 cells were treated with AA (10 μmol/L) for periods up to 72 h. Cell viability was determined by tetrazolium dye (MTT) assay. Morphological changes were assessed by phase-contrast microscopy. Markers of EMT, including E-cadherin and α-smooth muscle actin (α-SMA) were detected by indirect immunofluorescence stains. The BMP-7 and gremlin mRNA and protein expression in HK-2 cells were analyzed by quantitative real-time PCR (real-time RT-PCR) and western blotting after exposure to AA. The level of phosphorylated Smad1/5/8, a marker of BMP-7 activity, was also determined by western blot analysis. Cells were transfected with gremlin siRNA to determine the effects of gremlin knockdown on markers of EMT following treatment with AA. Our results indicated that AA-induced EMT was associated with acquisition of fibroblast-like cell shape, loss of E-cadherin, and increases of alpha-SMA and collagen type I. Interestingly, exposure of HK-2 cells to 10 μmol/L AA increased the mRNA and protein expression of gremlin in HK-2 cells. This increase was in parallel with a decrease in BMP-7 expression and a down-regulation of phosphorylated Smad1/5/8 protein levels. Moreover, transfection with siRNA to gremlin was able to recover BMP-7 signaling activity, and attenuate EMT-associated phenotypic changes induced by AA. Together, these observations strongly suggest that gremlin

  16. Temporal Bone CT: Improved Image Quality and Potential for Decreased Radiation Dose Using an Ultra-High-Resolution Scan Mode with an Iterative Reconstruction Algorithm.

    PubMed

    Leng, S; Diehn, F E; Lane, J I; Koeller, K K; Witte, R J; Carter, R E; McCollough, C H

    2015-09-01

    Radiation dose in temporal bone CT imaging can be high due to the requirement of high spatial resolution. In this study, we assessed whether CT imaging of the temporal bone by using an ultra-high-resolution scan mode combined with iterative reconstruction provides higher spatial resolution and lower image noise than a z-axis ultra-high-resolution mode. Patients with baseline temporal bone CT scans acquired by using a z-axis ultra-high-resolution protocol and a follow-up scan by using the ultra-high-resolution-iterative reconstruction technique were identified. Images of left and right temporal bones were reconstructed in the axial, coronal, and Poschl planes. Three neuroradiologists assessed the spatial resolution of the following structures: round and oval windows, incudomallear and incudostapedial joints, basal turn spiral lamina, and scutum. The paired z-axis ultra-high-resolution and ultra-high-resolution-iterative reconstruction images were displayed side by side in random order, with readers blinded to the imaging protocol. Image noise was compared in ROIs over the posterior fossa. We identified 8 patients, yielding 16 sets of temporal bone images (left and right). Three sets were excluded because the patient underwent surgery between the 2 examinations. Spatial resolution was comparable (Poschl) or slightly better (axial and coronal planes) with ultra-high-resolution-iterative reconstruction than with z-axis ultra-high-resolution. A paired t test indicated that noise was significantly lower with ultra-high-resolution-iterative reconstruction than with z-axis ultra-high-resolution (P < .001), with a mean noise reduction of 37% (range, 18%-49%). The ultra-high-resolution-iterative reconstruction scan mode has similar or slightly better resolution relative to the z-axis ultra-high-resolution mode for CT of the temporal bone but significantly (P < .01) lower image noise, which may enable the dose to be reduced by approximately 50%. © 2015 by American Journal of

  17. An approach for determining quantitative measures for bone volume and bone mass in the pediatric spina bifida population.

    PubMed

    Horenstein, Rachel E; Shefelbine, Sandra J; Mueske, Nicole M; Fisher, Carissa L; Wren, Tishya A L

    2015-08-01

    The pediatric spina bifida population suffers from decreased mobility and recurrent fractures. This study aimed to develop a method for quantifying bone mass along the entire tibia in youth with spina bifida. This will provide information about all potential sites of bone deficiencies. Computed tomography images of the tibia for 257 children (n=80 ambulatory spina bifida, n=10 non-ambulatory spina bifida, n=167 typically developing) were analyzed. Bone area was calculated at regular intervals along the entire tibia length and then weighted by calibrated pixel intensity for density weighted bone area. Integrals of density weighted bone area were used to quantify bone mass in the proximal and distal epiphyses and diaphysis. Group differences were evaluated using analysis of variance. Non-ambulatory children suffer from decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children (P≤0.001). Ambulatory children with spina bifida showed statistically insignificant differences in bone mass in comparison to typically developing children at these sites (P>0.5). This method provides insight into tibial bone mass distribution in the pediatric spina bifida population by incorporating information along the whole length of the bone, thereby providing more information than dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. This method can be applied to any population to assess bone mass distribution across the length of any long bone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Alendronate Treatment of the Brtl Osteogenesis Imperfecta Mouse Improves Femoral Geometry and Load Response Before Fracture but Decreases Predicted Material Properties and Has Detrimental Effects on Osteoblasts and Bone Formation

    PubMed Central

    Uveges, Thomas E.; Kozloff, Kenneth M.; Ty, Jennifer M.; Ledgard, Felicia; Raggio, Cathleen L.; Gronowicz, Gloria; Goldstein, Steven A.; Marini, Joan C.

    2009-01-01

    Long courses of bisphosphonates are widely administered to children with osteogenesis imperfecta (OI), although bisphosphonates do not block mutant collagen secretion and may affect bone matrix composition or structure. The Brtl mouse has a glycine substitution in col1a1 and is ideal for modeling the effects of bisphosphonate in classical OI. We treated Brtl and wildtype mice with alendronate (Aln; 0.219 mg/kg/wk, SC) for 6 or 12 wk and compared treated and untreated femora of both genotypes. Mutant and wildtype bone had similar responses to Aln treatment. Femoral areal BMD and cortical volumetric BMD increased significantly after 12 wk, but femoral length and growth curves were unaltered. Aln improved Brtl diaphyseal cortical thickness and trabecular number after 6 wk and cross-sectional shape after 12 wk. Mechanically, Aln significantly increased stiffness in wildtype femora and load to fracture in both genotypes after 12 wk. However, predicted material strength and elastic modulus were negatively impacted by 12 wk of Aln in both genotypes, and metaphyseal remnants of mineralized cartilage also increased. Brtl femoral brittleness was unimproved. Brtl osteoclast and osteoblast surface were unchanged by treatment. However, decreased mineral apposition rate and bone formation rate/bone surface and the flattened morphology of Brtl osteoblasts suggested that Aln impaired osteoblast function and matrix synthesis. We conclude that Aln treatment improves Brtl femoral geometry and load to fracture but decreases bone matrix synthesis and predicted material modulus and strength, with striking retention of mineralized cartilage. Beneficial and detrimental changes appear concomitantly. Limiting cumulative bisphosphonate exposure of OI bone will minimize detrimental effects. PMID:19113917

  19. Successful bone marrow transplantation reveals the lack of endothelial progenitor cells mobilization in a patient with critical limb ischemia: a case report.

    PubMed

    Cobellis, G; Botti, C; Taddeo, A; Silvestroni, A; Lillo, S; Da Ponte, A; Villa, M L; Sica, V; Della Bella, S

    2010-09-01

    Restoring blood flow to ischemic tissue is a prerequisite for treatment of ischemic diseases. Cell-based therapy based on bone marrow transplantation is a promising option for patients with critical limb ischemia (CLI). The efficacy of cell therapies to augment neovascularization seems to involve endothelial progenitor cells (EPCs); however, the mechanisms underlying the efficacy have not been fully elucidated. Herein we have described the case of a young patient with severe CLI, who experienced a 24-month beneficial clinical response to autologous bone marrow transplantation. The exceptional amelioration enabled him to perform standardized maximal treadmill exercise test that demonstrated lack of exercise-induced EPC mobilization, despite adequate stromal-derived factor 1 and vascular endothelial growth factor responses. Therefore, tissue ischemia is not sufficient to promote the recruitment of EPCs that have been demonstrated to be involved in the recovery from ischemia. The local implantation of marrow-derived elements may provide cells and/or trophic factors, which have the capacity to augment angiogenesis, opening new approaches to the etiopathogenesis of the disease. 2010 Elsevier Inc. All rights reserved.

  20. A High-Fat Diet Decreases Bone Mass in Growing Mice with Systemic Chronic Inflammation Induced by Low-Dose, Slow-Release Lipopolysaccharide Pellets

    USDA-ARS?s Scientific Manuscript database

    Chronic inflammation is linked to osteopenia or low bone mass, observed in a variety of physiological conditions such as aging and post-menopause with estrogen deficiency. Evidence suggests that obesity is also associated with low-grade chronic up-regulation of inflammatory cytokines. This study inv...

  1. LIM mineralization protein-1 potentiates bone morphogenetic protein responsiveness via a novel interaction with Smurf1 resulting in decreased ubiquitination of Smads.

    PubMed

    Sangadala, Sreedhara; Boden, Scott D; Viggeswarapu, Manjula; Liu, Yunshan; Titus, Louisa

    2006-06-23

    Development and repair of the skeletal system and other organs is highly dependent on precise regulation of bone morphogenetic proteins (BMPs), their receptors, and their intracellular signaling proteins known as Smads. The use of BMPs clinically to induce bone formation has been limited in part by the requirement of much higher doses of recombinant proteins in primates than were needed in cell culture or rodents. Therefore, control of cellular responsiveness to BMPs is now a critical area that is poorly understood. We determined that LMP-1, a LIM domain protein capable of inducing de novo bone formation, interacts with Smurf1 (Smad ubiquitin regulatory factor 1) and prevents ubiquitination of Smads. In the region of LMP responsible for bone formation, there is a motif that directly interacts with the Smurf1 WW2 domain and can effectively compete with Smad1 and Smad5 for binding. We have shown that small peptides containing this motif can mimic the ability to block Smurf1 from binding Smads. This novel interaction of LMP-1 with the WW2 domain of Smurf1 to block Smad binding results in increased cellular responsiveness to exogenous BMP and demonstrates a novel regulatory mechanism for the BMP signaling pathway.

  2. Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow

    PubMed Central

    Devi, Sapna; Wang, Yilin; Chew, Weng Keong; Lima, Ronald; A-González, Noelia; Mattar, Citra N.Z.; Chong, Shu Zhen; Schlitzer, Andreas; Bakocevic, Nadja; Chew, Samantha; Keeble, Jo L.; Goh, Chi Ching; Li, Jackson L.Y.; Evrard, Maximilien; Malleret, Benoit; Larbi, Anis; Renia, Laurent; Haniffa, Muzlifah; Tan, Suet Mien; Chan, Jerry K.Y.; Balabanian, Karl; Nagasawa, Takashi; Bachelerie, Françoise; Hidalgo, Andrés; Ginhoux, Florent; Kubes, Paul

    2013-01-01

    Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4–CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4–CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients. PMID:24081949

  3. Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration.

    PubMed

    Murakami, Masashi; Hayashi, Yuki; Iohara, Koichiro; Osako, Yohei; Hirose, Yujiro; Nakashima, Misako

    2015-01-01

    Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for pulp regeneration, although the volume of regenerated pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental pulp/dentin regeneration are stem cells from BM and AD tissue.

  4. The effect of in vivo mobilization of bone marrow stem cells on the pancreas of diabetic albino rats (a histological & immunohistochemical study).

    PubMed

    Ismail, Zeinab Mohamed Kamel; Kamel, Ashraf Mahmoud Fawzy; Yacoub, Mira Farouk Youssef; Aboulkhair, Alshaymaa Gamal

    2013-05-01

    The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus.

  5. Sarcopenia and fragility fractures: molecular and clinical evidence of the bone-muscle interaction.

    PubMed

    Tarantino, Umberto; Piccirilli, Eleonora; Fantini, Massimo; Baldi, Jacopo; Gasbarra, Elena; Bei, Roberto

    2015-03-04

    Bone and muscle tissues are in close relationship, and the aging process is a factor involved in the loss of the functionality of both bones and muscles.➤ Sarcopenia and osteoporosis are linked from a biological and functional perspective and are related to an increased fracture risk in the elderly.➤ The increased fracture risk in sarcopenic and osteoporotic subjects is due to the decline of muscle mass and strength, the decrease in bone mineral density, and limited mobility.

  6. Long-term Tolerance Toward Haploidentical Vascularized Composite Allograft Transplantation in a Canine Model Using Bone Marrow or Mobilized Stem Cells.

    PubMed

    Chang, Jeff; Graves, Scott S; Butts-Miwongtum, Tiffany; Sale, George E; Storb, Rainer; Mathes, David Woodbridge

    2016-12-01

    The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen-identical donor. In the present study, we extend those findings across a dog leukocyte antigen mismatched barrier. Eight recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n = 4) or granulocyte-colony stimulating factor mobilized peripheral blood stem cells (n = 4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days). In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5 to 7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease, whereas 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance toward its VCA (>90 weeks). The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance toward the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared with marrow HCT and an increase in the incidence of graft-versus-host disease.

  7. Bone Marrow-Derived Cell Accumulation in the Spinal Cord Is Independent of Peripheral Mobilization in a Mouse Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Peake, Kyle; Manning, John; Lewis, Coral-Ann; Tran, Kevin; Rossi, Fabio; Krieger, Charles

    2017-01-01

    Bone marrow-derived cells (BMDCs) are capable of migrating across the blood–brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100). We also used several concentrations of busulfan. We hypothesized that higher concentrations of busulfan and BMDC mobilization would increase numbers of GFP+ cells in the CNS. The doses of busulfan employed (60–125 mg/kg) all resulted in high levels of sustained chimerism (>85% 1 year post-transplant) in both the blood and BM of wild-type (WT) mice and an amyotrophic lateral sclerosis (ALS) mouse model. Moreover, cells accumulated within the CNS in a dose-, time-, and disease-dependent manner. Conditioning with the hydrophilic busulfan analog treosulfan, which is unable to cross the BBB efficiently, also resulted in a high degree of BM chimerism. However, few GFP+ BMDCs were found within the CNS of WT or ALS mice of treosulfan-conditioned mice. Mobilization of BMDCs into the circulation using GCSF and/or AMD3100 did not lead to increased accumulation of GFP+ BMDCs within the CNS of WT or ALS mice. Weekly analysis of BMDC accumulation revealed that BMDCs accumulated more rapidly and to a greater extent in the CNS of ALS mice conditioned with a high dose (125 mg/kg) of busulfan compared to a lower dose (80 mg/kg). The number of GFP+ BMDCs in the CNS labeling with the proliferation marker Ki67 increased in parallel with BMDC accumulation within the CNS. Our results indicate that establishment of high levels of blood and BM chimerism

  8. [Bone diseases].

    PubMed

    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.

  9. Bone formation: roles of genistein and daidzein

    USDA-ARS?s Scientific Manuscript database

    Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractu...

  10. Bone and bone turnover.

    PubMed

    Crofton, Patricia M

    2009-01-01

    Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

  11. Mobilization of endogenous bone marrow-derived stem cells in a thioacetamide-induced mouse model of liver fibrosis.

    PubMed

    El-Akabawy, Gehan; El-Mehi, Abeer

    2015-06-01

    The clinical significance of enhancing endogenous circulating haematopoietic stem cells is becoming increasingly recognized, and the augmentation of circulating stem cells using granulocyte-colony stimulating factor (G-CSF) has led to promising preclinical and clinical results for several liver fibrotic conditions. However, this approach is largely limited by cost and the infeasibility of maintaining long-term administration. Preclinical studies have reported that StemEnhance, a mild haematopoietic stem cell mobilizer, promotes cardiac muscle regeneration and remedies the manifestation of diabetes. However, the effectiveness of StemEnhance in ameliorating liver cirrhosis has not been studied. This study is the first to evaluate the beneficial effect of StemEnhance administration in a thioacetamide-induced mouse model of liver fibrosis. StemEnhance augmented the number of peripheral CD34-positive cells, reduced hepatic fibrosis, improved histopathological changes, and induced endogenous liver proliferation. In addition, VEGF expression was up-regulated, while TNF-α expression was down-regulated in thioacetamide-induced fibrotic livers after StemEnhance intake. These data suggest that StemEnhance may be useful as a potential therapeutic candidate for liver fibrosis by inducing reparative effects via mobilization of haematopoietic stem cells.

  12. Hydrostatic pressure decreases the proton mobility in the hydrated BaZr0.9Y0.1O3 proton conductor

    NASA Astrophysics Data System (ADS)

    Chen, Qianli; Braun, Artur; Ovalle, Alejandro; Savaniu, Cristian-Daniel; Graule, Thomas; Bagdassarov, Nikolai

    2010-07-01

    Impedance spectroscopy on the hydrated proton conductor BaZr0.9Y0.1O3 at high temperatures shows that the bulk proton conductivity activation energy Eb scales with the strain parameter ɛ, as achieved by hydrostatic pressures up to 2 GPa, suggesting that large lattices favor proton diffusivity. At high temperature, Eb increases upon pressure by 40%. The grain boundary activation energy Eg is around twice as Eb, indicating higher proton mobility in grain boundaries as a result of pressure induced sintering. An expanded lattice with strain parameter ɛ >1 should have lower Eb, suggesting that thin films expansive tensile strain could have larger proton conductivity.

  13. Extrahepatic stem cells mobilized from the bone marrow by the supplementation of branched-chain amino acids ameliorate liver regeneration in an animal model.

    PubMed

    Okabayashi, Takehiro; Shima, Yasuo; Sumiyoshi, Tatsuaki; Kozuki, Akihito; Iiyama, Tatsuo; Tokumaru, Teppei; Namikawa, Tsutomu; Sugimoto, Takeki; Takezaki, Yuka; Maeda, Hiromichi; Kobayashi, Michiya; Hanazaki, Kazuhiro

    2014-04-01

    In recent years, bone marrow (BM)-derived stem cell repopulation of injured organs has been increasingly observed; however, the extent to which it occurs and its clinical relevance remain unclear. Here, we investigated on the potential of extrahepatic stem cells to become hepatocytes using the treatment of the oral supplementation of branched-chain amino acids (BCAA). In the first, Sprague-Dawley (SD) rats were administered BCAA to promote liver regeneration; in the second, syngenic liver transplantations using wild-type SD rats that do not express green fluorescent protein (GFP) as syngenic donors and GFP-transgenic SD rats as recipients to confirm that an extrahepatic source of cells (GFP(+)) could repopulate the transplanted (GFP(-)) liver were performed. Treatment of the oral supplementation of BCAA for 2-3 weeks before transplantation to promote liver regeneration resulted in greater than 7 days graft volume, with extensive spotty conversion of a small wild-type graft to the recipient GFP(+) genotype. The treatment by oral supplementation of BCAA resulted in higher levels of CD34+SDF+c-kit+ stem cells in the blood and liver after liver transplantation. Liver repopulation could be achieved with hepatocytes that bone marrow-derived from stem cells proliferated. We have identified extrahepatic stem cell migration from the BM to the injured liver as a mechanism underlying liver regeneration that supports hepatocyte proliferation in diseased liver. Our results suggested that BCAA is able to mobilize a population of BM-derived cells that contribute to hepatic regeneration. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  14. Decreased survival of glioma patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile and cordless phones.

    PubMed

    Carlberg, Michael; Hardell, Lennart

    2014-10-16

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a "possible", human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997-2003 and 2007-2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2-2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4-2.9 and cordless phone use HR = 3.4, 95% CI = 1.04-11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007-1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999-1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.

  15. Macrophage inflammatory protein 1alpha enhances in a different manner adhesion of hematopoietic progenitor cells from bone marrow, cord blood, and mobilized peripheral blood.

    PubMed

    Suehiro, Y; Muta, K; Umemura, T; Abe, Y; Nishimura, J; Nawata, H

    1999-11-01

    Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, and thrombopoietin were reported to upregulate the adhesion of hematopoietic progenitors to immobilized fibronectin through activation of integrin alpha4beta1 and alpha5beta1. Macrophage inflammatory protein (MIP)-1alpha is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro. We asked if MIP-1alpha would modulate the adhesive phenotype of colony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cord blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparison with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1alpha significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1alpha were inhibited by blocking antibodies to integrin alpha4, alpha5, or beta1, and polymerization plus rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of MIP-1alpha on the adhesive phenotype of CFCs is mediated by modulation of the organization of integrin. The amount of MIP-1alpha receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in the adhesive response induced by MIP-1alpha. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect to maturation, integrin affinity, MIP-1alpha receptor expression, and regulation of MIP-1alpha signaling. Our data indicate that MIP-1alpha may affect migration, homing, and mobilization of hematopoietic progenitors by modulating the adhesive phenotype of these cells.

  16. The Effect of In Vivo Mobilization of Bone Marrow Stem Cells on the Pancreas of Diabetic Albino Rats (A Histological & Immunohistochemical Study)

    PubMed Central

    Ismail, Zeinab Mohamed Kamel; Kamel, Ashraf Mahmoud Fawzy; Yacoub, Mira Farouk Youssef; Aboulkhair, Alshaymaa Gamal

    2013-01-01

    Background and Objectives The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. Methods and Results Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. Conclusions This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus. PMID:24298369

  17. Bone graft

    MedlinePlus

    Autograft - bone; Allograft - bone; Fracture - bone graft; Surgery - bone graft; Autologous bone graft ... Fuse joints to prevent movement Repair broken bones (fractures) that have bone loss Repair injured bone that ...

  18. Bone Health and Osteoporosis.

    PubMed

    Lupsa, Beatrice C; Insogna, Karl

    2015-09-01

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

  19. Low‐Level Cadmium Exposure Is Associated With Decreased Bone Mineral Density and Increased Risk of Incident Fractures in Elderly Men: The MrOS Sweden Study

    PubMed Central

    Barregard, Lars; Sallsten, Gerd; Lundh, Thomas; Karlsson, Magnus K; Lorentzon, Mattias; Ohlsson, Claes; Mellström, Dan

    2015-01-01

    ABSTRACT One risk factor for osteoporosis that has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low‐level cadmium exposure, from diet and smoking, and bone mineral density (BMD) and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study, aged 70 to 81 years at inclusion (years 2002 to 2004), with reliable data on cadmium in urine (U‐Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using dual‐energy X‐ray absorptiometry (DXA) in the total body, hip, and lumbar spine. During the follow‐up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U‐Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U‐Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (eg, age, smoking, body mass index [BMI], and physical activity) were included in the models. We found significant negative associations between U‐Cd and BMD, with lower BMD (4% to 8%) for all sites in the fourth quartile of U‐Cd, using the first quartile as the reference. In addition, we found positive associations between U‐Cd and incident fractures, especially nonvertebral osteoporosis fractures in the fourth quartile of U‐Cd, with hazard ratios of 1.8 to 3.3 in the various models. U‐Cd as a continuous variable was significantly associated with nonvertebral osteoporosis fractures (adjusted hazard ratio 1.3 to 1.4 per μg Cd/g creatinine), also in never‐smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even

  20. Low-Level Cadmium Exposure Is Associated With Decreased Bone Mineral Density and Increased Risk of Incident Fractures in Elderly Men: The MrOS Sweden Study.

    PubMed

    Wallin, Maria; Barregard, Lars; Sallsten, Gerd; Lundh, Thomas; Karlsson, Magnus K; Lorentzon, Mattias; Ohlsson, Claes; Mellström, Dan

    2016-04-01

    One risk factor for osteoporosis that has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low-level cadmium exposure, from diet and smoking, and bone mineral density (BMD) and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study, aged 70 to 81 years at inclusion (years 2002 to 2004), with reliable data on cadmium in urine (U-Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using dual-energy X-ray absorptiometry (DXA) in the total body, hip, and lumbar spine. During the follow-up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U-Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U-Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (eg, age, smoking, body mass index [BMI], and physical activity) were included in the models. We found significant negative associations between U-Cd and BMD, with lower BMD (4% to 8%) for all sites in the fourth quartile of U-Cd, using the first quartile as the reference. In addition, we found positive associations between U-Cd and incident fractures, especially nonvertebral osteoporosis fractures in the fourth quartile of U-Cd, with hazard ratios of 1.8 to 3.3 in the various models. U-Cd as a continuous variable was significantly associated with nonvertebral osteoporosis fractures (adjusted hazard ratio 1.3 to 1.4 per μg Cd/g creatinine), also in never-smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even relatively low cadmium exposure

  1. Decreased levels of physical activity in adolescents with down syndrome are related with low bone mineral density: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Down syndrome (DS) has been described as one of the main contributors for low bone mineral density (BMD). Physical activity (PA) is a key factor in skeletal health and thus, PA levels might be associated to the risk of developing osteoporosis. Therefore, the aims were (1) to describe PA patterns in adolescents with DS compared to their counterparts and (2) to determine the relationships between PA and the risk of having low bone mass in adolescents with DS. Methods Nineteen adolescents (10 girls) with DS and 14 without disabilities (7 girls) participated in the study. Minutes in different PA intensities were objectively assessed with accelerometers (ActiTrainer). Moreover adolescents with DS were classified into PA tertiles taking into account the amount of total minutes of PA at any intensity, resulting in those performing low, medium or high of PA (lowPA, medPA and highPA). BMD was measured at the whole body, hip and lumbar spine with dual-energy X-ray absorptiometry and the BMD Z-score was calculated for each region taking into account age- and sex-matched reference data. Student’s unpaired t-tests and analysis of covariance were used to compare variables between different conditions (DS vs. control) and PA levels (low, medium and high). Results None of the adolescents with DS achieved the minimum of 60 min of daily moderate to vigorous PA (VPA) intensity recommended by PA guidelines; adolescents with DS group spent less time in sedentary and in VPA and more time in light PA than those without DS (p < 0.05). Adolescents with DS showed lower BMD Z-score values than those without (p < 0.05). Those adolescents with DS allocated in the lowPA tertile showed significant lower BMD Z-score at the hip and a general tendency towards lower BMD Z-score was found at whole body and lumbar spine compared to those in highPA tertile and (p < 0.05). Conclusions Adolescents with DS in the highPA tertile showed lower risk of developing future osteoporosis by having

  2. Hydrostatic pressure decreases the proton mobility in the hydrated BaZr{sub 0.9}Y{sub 0.1}O{sub 3} proton conductor

    SciTech Connect

    Chen Qianli; Braun, Artur; Ovalle, Alejandro; Savaniu, Cristian-Daniel; Graule, Thomas; Bagdassarov, Nikolai

    2010-07-26

    Impedance spectroscopy on the hydrated proton conductor BaZr{sub 0.9}Y{sub 0.1}O{sub 3} at high temperatures shows that the bulk proton conductivity activation energy E{sub b} scales with the strain parameter epsilon, as achieved by hydrostatic pressures up to 2 GPa, suggesting that large lattices favor proton diffusivity. At high temperature, E{sub b} increases upon pressure by 40%. The grain boundary activation energy Eg is around twice as E{sub b}, indicating higher proton mobility in grain boundaries as a result of pressure induced sintering. An expanded lattice with strain parameter epsilon>1 should have lower E{sub b}, suggesting that thin films expansive tensile strain could have larger proton conductivity.

  3. Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation.

    PubMed

    Lapierre, Valérie; Aupérin, Anne; Tayebi, Hakim; Chabod, Jacqueline; Saas, Philippe; Michalet, Mauricette; François, Sylvie; Garban, Frédéric; Giraud, Christine; Tramalloni, Dominique; Oubouzar, Nadia; Blaise, Didier; Kuentz, Matthieu; Robinet, Eric; Tiberghien, Pierre

    2002-08-15

    We have recently shown that the use of allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic stem cell transplantation (PBHSCT), as compared with bone marrow transplantation (BMT), is associated with increased titers of antibodies (Abs) directed against red blood cell ABO antigens. To further evaluate the influence of a G-CSF-mobilized PBHSCT graft on alloimmune Ab responses, we examined the frequency of anti-HLA Abs after transplantation in the setting of the same randomized study, comparing PBHSCT with BMT in adults. Anti-HLA Ab presence was determined by complement-dependent cytotoxicity assay (CDC) and flow cytometry in the recipient before and 30 days after transplantation as well as in the donor before graft donation. The use of PBHSCT was significantly associated with increased detection of anti-HLA immunoglobulin G (IgG) Abs early after transplantation as evidenced by flow cytometry (11 of 24 versus 4 of 27 transplant recipients, P =.03) and, less so, by CDC (5 of 24 versus 1 of 27 transplant recipients, P =.09). The difference between PBHSCT and BMT was further heightened when analysis was restricted to anti-HLA IgG Ab-negative donor/recipient pairs. In such a setting, early anti-HLA Ab was never detected after BMT but was repeatedly detected after PBHSCT (flow cytometry, 6 of 18 versus 0 of 17 transplant recipients, P =.02; CDC, 4 of 23 versus 0 of 26 transplant recipients, P =.04). Importantly, the PBHSCT-associated increase in anti-HLA Ab detection was observed despite a reduction in the median number of platelet-transfusion episodes per patient in PBHSC transplant versus BM transplant recipients (3 platelet-transfusion episodes [range, 1-21] in PBHSCT group vs 6 platelet-transfusion episodes [range, 3-33] in the BMT group; P =.02). In conclusion, this study strongly suggests that G-CSF-mobilized PBHSCT results in an increased incidence of circulating anti-HLA Abs and further confirms that the use of such a

  4. Benefits of Decreased Mortality Risk from Reductions in Primary Mobile Source Fine Particulate Matter: A Limited Data Approach for Urban Areas Worldwide.

    PubMed

    Greco, Susan L; Belova, Anna; Huang, Jin

    2016-09-01

    We developed an approach to estimate the public health benefits resulting from transportation projects or environmental actions that reduce mobile source fine particulate matter (PM2.5 ) in select urban areas worldwide when input data are limited or when a rapid order-of-magnitude assessment is needed. For a given reduction in direct PM2.5 emissions, we can use this approach to quantify (1) the subsequent reduction in ambient primary PM2.5 concentration in the urban area; (2) the public health benefits associated with mortality risk reductions, measured in terms of avoided premature deaths; and (3) the economic value of the reduced mortality risk. To illustrate our approach, we estimated the impact of a 100-metric-ton reduction in primary PM2.5 mobile source emissions in the year 2010 for 42 large, global cities. Our estimates of public health benefits and their economic value varied by city, as did the sensitivity to key assumptions and inputs. The estimated number of premature deaths avoided per 100-metric-ton reduction in PM2.5 emissions ranged from 12 to 202. City-level variability in these estimates was driven by the magnitude of the reduction in ambient PM2.5 concentration, the size of the urban population, and the baseline PM2.5 concentration. The economic value of mortality risk reductions per 100-metric-ton reduction in PM2.5 emissions ranged from $2 million to $328 million in 2010 U.S. dollars. Income per capita was the most important driver of the variability in the economic values across countries.

  5. Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

    SciTech Connect

    Kosheverova, Vera V.; Kamentseva, Rimma S.; Gonchar, Ilya V.; Kharchenko, Marianna V.; Kornilova, Elena S.

    2016-04-22

    Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

  6. Decreased Survival of Glioma Patients with Astrocytoma Grade IV (Glioblastoma Multiforme) Associated with Long-Term Use of Mobile and Cordless Phones

    PubMed Central

    Carlberg, Michael; Hardell, Lennart

    2014-01-01

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a “possible”, human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997–2003 and 2007–2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2–2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4–2.9 and cordless phone use HR = 3.4, 95% CI = 1.04–11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007–1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999–1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines. PMID:25325361

  7. Long-term outcomes after transplantation of HLA-identical related G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow.

    PubMed

    Mielcarek, Marco; Storer, Barry; Martin, Paul J; Forman, Stephen J; Negrin, Robert S; Flowers, Mary E; Inamoto, Yoshihiro; Chauncey, Thomas R; Storb, Rainer; Appelbaum, Frederick R; Bensinger, William I

    2012-03-15

    Between 1996 and 1999, 172 patients (median age, 42 years) with hematologic malignancies were randomly assigned to receive either HLA-identical related bone marrow or G-CSF-mobilized peripheral blood mononuclear cells (G-PBMCs) after myeloablative conditioning. Early results showed that transplantation of G-PBMCs, compared with marrow, was associated with significantly superior 2-year disease-free survival (DFS) and overall survival. Ten-year follow-up showed a sustained DFS benefit associated with G-PBMCs (mortality or relapse hazard ratio, 0.64; 95% confidence interval, 0.4-1.0; P = .03), although the likelihood of overall survival was not significantly different between the 2 groups (mortality hazard ratio, 0.75; 95% confidence interval, 0.5-1.2; P = .20). The 10-year cumulative incidence of chronic GVHD and the duration of systemic immunosuppression were similar in the 2 groups. In summary, transplantation of HLA-identical related G-PBMCs, compared with marrow, was associated with superior short-term and long-term DFS, and there was no evidence that this benefit was outweighed by GVHD-related late mortality.

  8. Good maintenance of exercise-induced bone gain with decreased training of female tennis and squash players: a prospective 5-year follow-up study of young and old starters and controls.

    PubMed

    Kontulainen, S; Kannus, P; Haapasalo, H; Sievänen, H; Pasanen, M; Heinonen, A; Oja, P; Vuori, I

    2001-02-01

    This prospective 5-year follow-up study of 64 adult female racquet sports players and 27 controls assessed the changes in the playing-to-nonplaying arm bone mineral content (BMC) differences to answer three questions: (1) Are training-induced bone gains lost with decreased training? (2) Is the bone response to decreased training different if the playing career has been started before or at puberty rather than after it? (3) Are the possible bone changes related to the changes in training? The players were divided into two groups according to the starting age of their tennis or squash playing. The mean starting age was 10.5 years (SD, 2.2) among the players who had started training before or at menarche (young starters; n = 36) while 26.4 years (SD, 8.0) among those players who had begun training a minimum of 1 year after menarche (old starters; n = 28). At baseline of the 5-year follow-up, the mean age of the young starters was 21.6 years (SD, 7.6) and that of old starters was 39.4 years (SD, 10.5). During the follow-up, the young starters had reduced the average training frequency from 4.7 times a week (2.7) to 1.4 times a week (1.3) and the old starters from 4.0 times a week (1.4) to 2.0 times a week (1.4), respectively. The 5-year follow-up revealed that despite reduced training the exercise-induced bone gain was well maintained in both groups of players regardless of their clearly different starting age of activity and different amount of exercise-induced bone gain. The gain was still 1.3-2.2 times greater in favor of the young starters (at the follow-up, the dominant-to-nondominant arm BMC difference was 22% [8.4] in the humeral shaft of the young starters versus 10% [3.8] in the old starters, and 3.5% [2.4] in controls). In the players, changes in training were only weakly related to changes in the side-to-side BMC difference (r(s) = 0.05-0.34, all NS), and this was true even among the players who had stopped training completely a minimum 1 year before the

  9. Short-Term Exposure to Electromagnetic Fields Generated by Mobile Phone Jammers Decreases the Fasting Blood Sugar in Adult Male Rats.

    PubMed

    Shekoohi Shooli, F; Mortazavi, S A R; Jarideh, S; Nematollahii, S; Yousefi, F; Haghani, M; Mortazavi, S M J; Shojaei-Fard, M B

    2016-03-01

    Substantial evidence indicates that exposure to electromagnetic fields (EMF) above certain levels can affect human health through triggering some biological responses. According to WHO, short-term exposure to EMF at the levels present in the home/environment do not cause any apparent detrimental effects in healthy individuals. However, now, there is a debate on whether long-term exposure to low level EMF can evoke detrimental biological responses. Although based on the Communications Act of 1934, selling, advertising, using, or importing mobile jammers which block cell phone calls and text messages are illegal acts, in some countries these devices are being used for security purpose and for prevention of cheating during examinations. In this study 30 male Wistar rats were randomly divided into 3 groups of 10 each. The control group received no radiation. The sham exposure group was exposed to a switched-off jammer device. After fasting for 12 hours, the exposure group was exposed to EMFs at a distance of 50 cm from the jammer. Blood samples were collected from the tail vein after 24, 48 and72 hours and fasting blood sugar was measured by using a common blood glucose monitor (BIONIME GM110, Taiwan). The significance level was considered 5% and SPSS Ver. 21 was used for statistical analysis. The data were analyzed by ANOVA followed by Tukey's test. A statistically significant difference was observed between blood sugar level in the control and exposure groups after 24, 48 and 72 hours of continuous irradiation (p values were <0.001, <0.001 and 0.002, respectively). No significant difference was found between the level of fasting blood sugar in control and sham groups. Short-term exposure to electromagnetic field generated by mobile phone jammer can reduce blood sugar level in adult male rats. These findings, in contrast with our previous results, lead us to this conclusion that the use of these signal blocking devices in very specific circumstances may have some

  10. Short–Term Exposure to Electromagnetic Fields Generated by Mobile Phone Jammers Decreases the Fasting Blood Sugar in Adult Male Rats

    PubMed Central

    Shekoohi Shooli, F.; Mortazavi, S. A. R.; Jarideh, S.; Nematollahii, S.; Yousefi, F.; Haghani, M.; Mortazavi, S. M. J.; Shojaei-fard, M. B.

    2016-01-01

    Background Substantial evidence indicates that exposure to electromagnetic fields (EMF) above certain levels can affect human health through triggering some biological responses. According to WHO, short-term exposure to EMF at the levels present in the home/environment do not cause any apparent detrimental effects in healthy individuals. However, now, there is a debate on whether long-term exposure to low level EMF can evoke detrimental biological responses. Although based on the Communications Act of 1934, selling, advertising, using, or importing mobile jammers which block cell phone calls and text messages are illegal acts, in some countries these devices are being used for security purpose and for prevention of cheating during examinations. Methods In this study 30 male Wistar rats were randomly divided into 3 groups of 10 each. The control group received no radiation. The sham exposure group was exposed to a switched-off jammer device. After fasting for 12 hours, the exposure group was exposed to EMFs at a distance of 50 cm from the jammer. Blood samples were collected from the tail vein after 24, 48 and72 hours and fasting blood sugar was measured by using a common blood glucose monitor (BIONIME GM110, Taiwan). The significance level was considered 5% and SPSS Ver. 21 was used for statistical analysis. The data were analyzed by ANOVA followed by Tukey’s test. Results A statistically significant difference was observed between blood sugar level in the control and exposure groups after 24, 48 and 72 hours of continuous irradiation (p values were <0.001, <0.001 and 0.002, respectively). No significant difference was found between the level of fasting blood sugar in control and sham groups. Conclusion Short-term exposure to electromagnetic field generated by mobile phone jammer can reduce blood sugar level in adult male rats. These findings, in contrast with our previous results, lead us to this conclusion that the use of these signal blocking devices in very

  11. Hyponatremia and bone disease.

    PubMed

    Negri, Armando Luis; Ayus, Juan Carlos

    2016-09-24

    Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement

  12. Decreased hypertrophic differentiation accompanies enhanced matrix formation in co-cultures of outer meniscus cells with bone marrow mesenchymal stromal cells

    PubMed Central

    2012-01-01

    Introduction The main objective of this study was to determine whether meniscus cells from the outer (MCO) and inner (MCI) regions of the meniscus interact similarly to or differently with mesenchymal stromal stem cells (MSCs). Previous study had shown that co-culture of meniscus cells with bone marrow-derived MSCs result in enhanced matrix formation relative to mono-cultures of meniscus cells and MSCs. However, the study did not examine if cells from the different regions of the meniscus interacted similarly to or differently with MSCs. Methods Human menisci were harvested from four patients undergoing total knee replacements. Tissue from the outer and inner regions represented pieces taken from one third and two thirds of the radial distance of the meniscus, respectively. Meniscus cells were released from the menisci after collagenase treatment. Bone marrow MSCs were obtained from the iliac crest of two patients after plastic adherence and in vitro culture until passage 2. Primary meniscus cells from the outer (MCO) or inner (MCI) regions of the meniscus were co-cultured with MSCs in three-dimensional (3D) pellet cultures at 1:3 ratio, respectively, for 3 weeks in the presence of serum-free chondrogenic medium containing TGF-β1. Mono-cultures of MCO, MCI and MSCs served as experimental control groups. The tissue formed after 3 weeks was assessed biochemically, histochemically and by quantitative RT-PCR. Results Co-culture of inner (MCI) or outer (MCO) meniscus cells with MSCs resulted in neo-tissue with increased (up to 2.2-fold) proteoglycan (GAG) matrix content relative to tissues formed from mono-cultures of MSCs, MCI and MCO. Co-cultures of MCI or MCO with MSCs produced the same amount of matrix in the tissue formed. However, the expression level of aggrecan was highest in mono-cultures of MSCs but similar in the other four groups. The DNA content of the tissues from co-cultured cells was not statistically different from tissues formed from mono-cultures of

  13. The effects of two non-steroidal anti-inflammatory drugs on the mobility of laying hens with keel bone fractures.

    PubMed

    Nasr, Mohammed Af; Nicol, Christine J; Wilkins, Lindsay; Murrell, Joanna C

    2015-03-01

    Investigate the effects of administration of meloxicam and carprofen on the mobility of hens with and without keel fractures. Within each of two experiments a 'blinded' randomised cross over design whereby birds received either the test drug (carprofen or meloxicam) or saline. Two groups of Lohman Brown hens with and without keel bone fractures. The first group (n = 63) was treated with carprofen 25 mg kg(-1) and saline subcutaneously, twice. The second group (n = 40) was treated with meloxicam (5 mg kg(-1) ) and saline subcutaneously. The latency of birds to fly down from perches 50, 100 and 150 cm above the ground was measured after each treatment. Data from experiment 1 and 2 were analysed separately; the effects of drug treatment compared with saline on landing time for birds with and without keel bone fractures were evaluated using MLwiN. In both experiments latency to fly down from perches was longer in hens with keel fractures and there was a significant interaction between perch height and fracture status. For carprofen, at the 50 cm, 100 cm and 150 cm perch heights, birds with fractures took (mean ± SD) 2.5 ± 2.9, 6.8 ± 9.7 and 11.5 ± 13.2 seconds respectively to fly down compared with 1.3 ± 0.5, 2.3 ± 1.2 and 4.2 ± 3.1 seconds for birds without fractures. For meloxicam, at the 50 cm, 100 cm and 150 cm perch heights, birds with fractures took 2.9 ± 2.5, 49.8 ± 85.4 and 100.3 ± 123.6 seconds respectively compared with 0.7 ± 0.5, 2.5 ± 7.1 and 3.0 ± 4.6 seconds to fly down for birds without fractures. There was no significant effect of carprofen or meloxicam treatment. These data provide further confirmation that keel fractures reduce the willingness of birds to move from perches. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  14. Polymorphism of LRP5, but not of TNFRSF11B, is associated with a decrease in bone mineral density in postmenopausal Maya-Mestizo women.

    PubMed

    Canto-Cetina, Thelma; Polanco Reyes, Lucila; González Herrera, Lizbeth; Rojano-Mejía, David; Coral-Vázquez, Ramón Mauricio; Coronel, Agustín; Canto, Patricia

    2013-01-01

    Osteoporosis is a complex disease characterized principally by low bone mineral density (BMD), which is determined by an interaction of genetic, metabolic, and environmental factors. The aim of this study was to analyze the possible association among one polymorphism of LRP5 and three polymorphisms of TNFRSF11B as well as their haplotypes with BMD variations in Maya-Mestizo postmenopausal women. We studied 583 postmenopausal women of Maya-Mestizo ethnic origin. A structured questionnaire for risk factors was applied and BMD was measured in lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. One single-nucleotide polymorphism of LRP5 (rs3736228, p.A1330V) and three of TNFRSF11B (rs4355801, rs2073618, and rs6993813) were studied using real-time PCR allelic discrimination for genotyping. Differences between the means of the BMDs according to the genotype were analyzed with covariance. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis of TNFRSF11B was conducted. The Val genotype of the rs3736228 (p.A1330V) of LRP5 was significantly associated with BMD variations at the LS, TH, and FN. None of the three polymorphisms of TNFRSF11B was associated with BMD variations. Our results show that p.A1330V was significantly associated with BMD variations at all three skeletal sites analyzed; the Val allele and the Val/Val genotype were those most frequently found in our population. Copyright © 2013 Wiley Periodicals, Inc.

  15. Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model.

    PubMed

    Calió, Michele Longoni; Marinho, Darci Sousa; Ko, Gui Mi; Ribeiro, Renata Rodrigues; Carbonel, Adriana Ferraz; Oyama, Lila Missae; Ormanji, Milene; Guirao, Tatiana Pinoti; Calió, Pedro Luiz; Reis, Luciana Aparecida; Simões, Manuel de Jesus; Lisbôa-Nascimento, Telma; Ferreira, Alice Teixeira; Bertoncini, Clélia Rejane Antônio

    2014-05-01

    Stroke is the most common cause of motor disabilities and is a major cause of mortality worldwide. Adult stem cells have been shown to be effective against neuronal degeneration through mechanisms that include both the recovery of neurotransmitter activity and a decrease in apoptosis and oxidative stress. We chose the lineage stroke-prone spontaneously hypertensive rat (SHRSP) as a model for stem cell therapy. SHRSP rats can develop such severe hypertension that they generally suffer a stroke at approximately 1 year of age. The aim of this study was to evaluate whether mesenchymal stem cells (MSCs) decrease apoptotic death and oxidative stress in existing SHRSP brain tissue. The results of qRT-PCR assays showed higher levels of the antiapoptotic Bcl-2 gene in the MSC-treated animals, compared with untreated. Our study also showed that superoxide, apoptotic cells, and by-products of lipid peroxidation decreased in MSC-treated SHRSP to levels similar those found in the animal controls, Wistar Kyoto rats. In addition, we saw a repair of morphological damage at the hippocampal region after MSC transplantation. These data suggest that MSCs have neuroprotective and antioxidant potential in stroke-prone spontaneously hypertensive rats.

  16. Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.

    PubMed

    Bashey, Asad; Zhang, Mei-Jie; McCurdy, Shannon R; St Martin, Andrew; Argall, Trevor; Anasetti, Claudio; Ciurea, Stefan O; Fasan, Omotayo; Gaballa, Sameh; Hamadani, Mehdi; Munshi, Pashna; Al Malki, Monzr M; Nakamura, Ryotaro; O'Donnell, Paul V; Perales, Miguel-Angel; Raj, Kavita; Romee, Rizwan; Rowley, Scott; Rocha, Vanderson; Salit, Rachel B; Solh, Melhem; Soiffer, Robert J; Fuchs, Ephraim Joseph; Eapen, Mary

    2017-09-10

    Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P < .001) and chronic (HR, 0.35; P < .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up.

  17. Cell density-dependent changes in intracellular Ca2+ mobilization via the P2Y2 receptor in rat bone marrow stromal cells.

    PubMed

    Ichikawa, Jun; Gemba, Hisae

    2009-05-01

    Bone marrow stromal cells (BMSCs) are an interesting subject of research because they have characteristics of mesenchymal stem cells. We investigated intracellular Ca(2+) signaling in rat BMSCs. Agonists for purinergic receptors increased intracellular Ca(2+) levels ([Ca(2+)](i)). The order of potency followed ATP = UTP > ADP = UDP. ATP-induced rise in [Ca(2+)](i) was suppressed by U73122 and suramin, but not by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), suggesting the functional expression of G protein-coupled P2Y(2) receptors. RT-PCR and immunohistochemical studies also showed the expression of P2Y(2) receptors. [Ca(2+)](i) response to UTP changed with cell density. The UTP-induced rise in [Ca(2+)](i) was greatest at high density. V(max) (maximum Ca(2+) response) and EC(50) (agonist concentration that evokes 50% of V(max)) suggest that the amount and property of P2Y(2) receptors were changed by cell density. Note that UTP induced Ca(2+) oscillation at only medium cell density. Pharmacological studies indicated that UTP-induced Ca(2+) oscillation required Ca(2+) influx by store-operated Ca(2+) entry. Carbenoxolone, a gap junction blocker, enhanced Ca(2+) oscillation. Immunohistochemical and quantitative real-time PCR studies revealed that proliferating cell nuclear antigen (PCNA)-positive cells declined but the mRNA expression level of the P2Y(2) receptor increased as cell density increased. Co-application of fetal calf serum with UTP induced Ca(2+) oscillation at high cell density. These results suggest that the different patterns observed for [Ca(2+)](i) mobilization with respect to cell density may be associated with cell cycle progression.

  18. Effects of autologous SCF- and G-CSF-mobilized bone marrow stem cells on hypoxia-inducible factor-1 in rats with ischemia-reperfusion renal injury.

    PubMed

    Bi, L Y; Zhao, D A; Yang, D S; Guo, J G; Liang, B; Zhang, R X; Zhao, J L; Bai, H T; Li, S J

    2015-04-27

    To explore the mechanism whereby stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) jointly mobilize bone marrow stem cells (BMSCs) and promote kidney repair, male Sprague-Dawley rats were randomly assigned into 4 groups. In the treatment control group, rats were administered SCF (200 μg·kg(-1)·day(-1)) and G-CSF (50 μg·kg-1·day-1) for 5 days. In the treatment group, RIRI models were established, and 6 h later, SCF (200 μg·kg(-1)·day(-1)) and G-CSF (50 μg·kg(-1)·day(-1)) were administered for 5 days. In the model and treatment groups, tubular epithelial cell degeneration and necrosis were noticed, but the extent of repair in the treatment group was significantly better than in the model group. Five days after the operation, renal tissue CD34+ cells significantly increased in the model and treatment groups compared with the control and treatment control groups. HIF-1α, VEGF, and EPO expression in treatment groups increased significantly compared with the other groups. HIF- 1α, VEGF, EPO expression in the treatment control group increased significantly compared with the control group. Joint use of SCF and G-CSF increased the number of BMSCs in damaged kidney tissue and reduced the degree of renal tissue damage. BMSCs promote increased HIF-1α expression in renal tissue. Increased kidney tissue HIF- 1α and its target gene products VEGF and EPO expression possibly induce SCF and G-CSF to promote acute tubular necrosis repair.

  19. Cancer to bone: a fatal attraction

    PubMed Central

    Weilbaecher, Katherine N.; Guise, Theresa A.; McCauley, Laurie K.

    2013-01-01

    When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases. Basic findings of tumour–bone interactions have uncovered numerous therapeutic opportunities that focus on the bone microenvironment to prevent and treat bone metastases. PMID:21593787

  20. Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring.

    PubMed

    Yüksel, Murat; Nazıroğlu, Mustafa; Özkaya, Mehmet Okan

    2016-05-01

    We investigated the effects of mobile phone (900 and 1800 MHz)- and Wi-Fi (2450 MHz)-induced electromagnetic radiation (EMR) exposure on uterine oxidative stress and plasma hormone levels in pregnant rats and their offspring. Thirty-two rats and their forty newborn offspring were divided into the following four groups according to the type of EMR exposure they were subjected to: the control, 900, 1800, and 2450 MHz groups. Each experimental group was exposed to EMR for 60 min/day during the pregnancy and growth periods. The pregnant rats were allowed to stand for four generations (total 52 weeks) before, plasma and uterine samples were obtained. During the 4th, 5th, and 6th weeks of the experiment, plasma and uterine samples were also obtained from the developing rats. Although uterine lipid peroxidation increased in the EMR groups, uterine glutathione peroxidase activity (4th and 5th weeks) and plasma prolactin levels (6th week) in developing rats decreased in these groups. In the maternal rats, the plasma prolactin, estrogen, and progesterone levels decreased in the EMR groups, while the plasma total oxidant status, and body temperatures increased. There were no changes in the levels of reduced glutathione, total antioxidants, or vitamins A, C, and E in the uterine and plasma samples of maternal rats. In conclusion, although EMR exposure decreased the prolactin, estrogen, and progesterone levels in the plasma of maternal rats and their offspring, EMR-induced oxidative stress in the uteri of maternal rats increased during the development of offspring. Mobile phone- and Wi-Fi-induced EMR may be one cause of increased oxidative uterine injury in growing rats and decreased hormone levels in maternal rats. TRPV1 cation channels are the possible molecular pathways responsible for changes in the hormone, oxidative stress, and body temperature levels in the uterus of maternal rats following a year-long exposure to electromagnetic radiation exposure from mobile phones and

  1. Inflammation, bone loss and fracture risk in spondyloarthritis

    PubMed Central

    Briot, Karine; Roux, Christian

    2015-01-01

    Osteoporosis (ie, low bone mineral density) is common in ankylosing spondylitis, related to both systemic inflammation and decreased mobility. Vertebral fracture risk is increased; acute back pain in these patients is not always a flare-up of the disease, as it can be related to bone complications. Intervertebral disc fractures in the ankylosed spine are associated with severe neurological complications. As expected from pathophysiology, treatments effective against inflammation have a positive effect on bone, and prospective open studies have shown that tumour-necrosis-factor blockers can improve bone mineral density at the spine and the hip. There is so far no evidence of a decreased risk of fractures with such treatment. PMID:26509065

  2. Can Whole-Body Cryotherapy with Subsequent Kinesiotherapy Procedures in Closed Type Cryogenic Chamber Improve BASDAI, BASFI, and Some Spine Mobility Parameters and Decrease Pain Intensity in Patients with Ankylosing Spondylitis?

    PubMed Central

    Stanek, Agata; Cholewka, Armand; Gadula, Jolanta; Drzazga, Zofia; Sieron, Aleksander; Sieron-Stoltny, Karolina

    2015-01-01

    The present study investigated whether whole-body cryotherapy (WBC) procedures could potentially have more beneficial effects on index of BASDAI and BASFI, pain intensity, and spine mobility parameters: Ott test, modified Schober test, chest expansion in ankylosing spondylitis (AS) patients, than kinesiotherapy procedures used separately. AS patients were exposed to a cycle of WBC procedures lasting 3 minutes a day, with a subsequent 60 minutes of kinesiotherapy or 60 minutes of kinesiotherapy only, for 10 consecutive days excluding weekend. After the completion of the cycle of WBC procedures with subsequent kinesiotherapy in the AS patients, BASDAI index decreased about 40% in comparison with the input value, whereas in the group of patients who received only kinesiotherapy it decreased only about 15% in comparison with the input value. After the completion of the treatment in the WBC group, BASFI index decreased about 30% in comparison with the input value, whereas in the kinesiotherapy group it only decreased about 16% in comparison with the input value. The important conclusion was that, in WBC group with subsequent kinesiotherapy, we observed on average about twice better results than in the group treated only by kinesiotherapy. PMID:26273618

  3. Can Whole-Body Cryotherapy with Subsequent Kinesiotherapy Procedures in Closed Type Cryogenic Chamber Improve BASDAI, BASFI, and Some Spine Mobility Parameters and Decrease Pain Intensity in Patients with Ankylosing Spondylitis?

    PubMed

    Stanek, Agata; Cholewka, Armand; Gadula, Jolanta; Drzazga, Zofia; Sieron, Aleksander; Sieron-Stoltny, Karolina

    2015-01-01

    The present study investigated whether whole-body cryotherapy (WBC) procedures could potentially have more beneficial effects on index of BASDAI and BASFI, pain intensity, and spine mobility parameters: Ott test, modified Schober test, chest expansion in ankylosing spondylitis (AS) patients, than kinesiotherapy procedures used separately. AS patients were exposed to a cycle of WBC procedures lasting 3 minutes a day, with a subsequent 60 minutes of kinesiotherapy or 60 minutes of kinesiotherapy only, for 10 consecutive days excluding weekend. After the completion of the cycle of WBC procedures with subsequent kinesiotherapy in the AS patients, BASDAI index decreased about 40% in comparison with the input value, whereas in the group of patients who received only kinesiotherapy it decreased only about 15% in comparison with the input value. After the completion of the treatment in the WBC group, BASFI index decreased about 30% in comparison with the input value, whereas in the kinesiotherapy group it only decreased about 16% in comparison with the input value. The important conclusion was that, in WBC group with subsequent kinesiotherapy, we observed on average about twice better results than in the group treated only by kinesiotherapy.

  4. Calcium and bone disease

    PubMed Central

    Blair, Harry C.; Robinson, Lisa J.; Huang, Christopher L.-H.; Sun, Li; Friedman, Peter A.; Schlesinger, Paul H.; Zaidi, Mone

    2013-01-01

    Calcium transport and calcium signaling are of basic importance in bone cells. Bone is the major store of calcium and a key regulatory organ for calcium homeostasis. Bone, in major part, responds to calcium-dependent signals from the parathyroids and via vitamin D metabolites, although bone retains direct response to extracellular calcium if parathyroid regulation is lost. Improved understanding of calcium transporters and calcium-regulated cellular processes has resulted from analysis of genetic defects, including several defects with low or high bone mass. Osteoblasts deposit calcium by mechanisms including phosphate and calcium transport with alkalinization to absorb acid created by mineral deposition; cartilage calcium mineralization occurs by passive diffusion and phosphate production. Calcium mobilization by osteoclasts is mediated by acid secretion. Both bone forming and bone resorbing cells use calcium signals as regulators of differentiation and activity. This has been studied in more detail in osteoclasts, where both osteoclast differentiation and motility are regulated by calcium. PMID:21674636

  5. Anti-Inflammatory Effects of IL-27 in Zymosan-Induced Peritonitis: Inhibition of Neutrophil Recruitment Partially Explained by Impaired Mobilization from Bone Marrow and Reduced Chemokine Levels

    PubMed Central

    Liu, Francesca Diane M.; Schwab, Jan M.; Hamann, Alf

    2015-01-01

    Rapid activation of the innate immune system is critical for an efficient host response to invading pathogens. However, the inflammatory reaction has to be strictly controlled to minimize harmful immunopathology. A number of mediators including the cytokine interleukin-27 (IL-27) appear to be responsible for limitation and resolution of inflammation. Despite increasing knowledge of its suppressive effects on T cells, the influence on neutrophils and macrophages is poorly understood. To determine the role of IL-27 in innate immune responses we analysed the effect of IL-27 in a T cell independent model of zymosan-induced peritonitis. Early administration of recombinant IL-27 strongly reduced the number of neutrophils recruited to the peritoneal cavity after zymosan application as well as the neutrophil frequency in the blood. Simultaneously, IL-27 reduced the release of neutrophils from the bone marrow upon inflammation. Although cytokine levels were not affected by IL-27 treatment, the levels of the chemokines KC, MCP-1 and MIP-1α in the peritoneal fluid were strongly decreased. These findings demonstrate that IL-27 is able to control mobilisation and recruitment of neutrophils into the peritoneal cavity and identify a novel mechanism to limit inflammation caused by innate immune cells. PMID:26360023

  6. Anti-Inflammatory Effects of IL-27 in Zymosan-Induced Peritonitis: Inhibition of Neutrophil Recruitment Partially Explained by Impaired Mobilization from Bone Marrow and Reduced Chemokine Levels.

    PubMed

    Watzlawick, Ralf; Kenngott, Elisabeth E; Liu, Francesca Diane M; Schwab, Jan M; Hamann, Alf

    2015-01-01

    Rapid activation of the innate immune system is critical for an efficient host response to invading pathogens. However, the inflammatory reaction has to be strictly controlled to minimize harmful immunopathology. A number of mediators including the cytokine interleukin-27 (IL-27) appear to be responsible for limitation and resolution of inflammation. Despite increasing knowledge of its suppressive effects on T cells, the influence on neutrophils and macrophages is poorly understood. To determine the role of IL-27 in innate immune responses we analysed the effect of IL-27 in a T cell independent model of zymosan-induced peritonitis. Early administration of recombinant IL-27 strongly reduced the number of neutrophils recruited to the peritoneal cavity after zymosan application as well as the neutrophil frequency in the blood. Simultaneously, IL-27 reduced the release of neutrophils from the bone marrow upon inflammation. Although cytokine levels were not affected by IL-27 treatment, the levels of the chemokines KC, MCP-1 and MIP-1α in the peritoneal fluid were strongly decreased. These findings demonstrate that IL-27 is able to control mobilisation and recruitment of neutrophils into the peritoneal cavity and identify a novel mechanism to limit inflammation caused by innate immune cells.

  7. Extracellular high mobility group box 1 plays a role in the effect of bone marrow mononuclear cell transplantation for heart failure.

    PubMed

    Kaneko, Masahiro; Shintani, Yasunori; Narita, Takuya; Ikebe, Chiho; Tano, Nobuko; Yamahara, Kenichi; Fukushima, Satsuki; Coppen, Steven R; Suzuki, Ken

    2013-01-01

    Transplantation of unfractionated bone marrow mononuclear cells (BMCs) repairs and/or regenerates the damaged myocardium allegedly due to secretion from surviving BMCs (paracrine effect). However, donor cell survival after transplantation is known to be markedly poor. This discrepancy led us to hypothesize that dead donor BMCs might also contribute to the therapeutic benefits from BMC transplantation. High mobility group box 1 (HMGB1) is a nuclear protein that stabilizes nucleosomes, and also acts as a multi-functional cytokine when released from damaged cells. We thus studied the role of extracellular HMGB1 in the effect of BMC transplantation for heart failure. Four weeks after coronary artery ligation in female rats, syngeneic male BMCs (or PBS only as control) were intramyocardially injected with/without anti-HMGB1 antibody or control IgG. One hour after injection, ELISA showed that circulating extracellular HMGB1 levels were elevated after BMC transplantation compared to the PBS injection. Quantitative donor cell survival assessed by PCR for male-specific sry gene at days 3 and 28 was similarly poor. Echocardiography and catheterization showed enhanced cardiac function after BMC transplantation compared to PBS injection at day 28, while this effect was abolished by antibody-neutralization of HMGB1. BMC transplantation reduced post-infarction fibrosis, improved neovascularization, and increased proliferation, while all these effects in repairing the failing myocardium were eliminated by HMGB1-inhibition. Furthermore, BMC transplantation drove the macrophage polarization towards alternatively-activated, anti-inflammatory M2 macrophages in the heart at day 3, while this was abolished by HMGB1-inhibition. Quantitative RT-PCR showed that BMC transplantation upregulated expression of an anti-inflammatory cytokine IL-10 in the heart at day 3 compared to PBS injection. In contrast, neutralizing HMGB1 by antibody-treatment suppressed this anti-inflammatory expression

  8. Anorexia Nervosa and Bone

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiologic estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

  9. Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex.

    PubMed

    Ratajczak, M Z; Lee, H; Wysoczynski, M; Wan, W; Marlicz, W; Laughlin, M J; Kucia, M; Janowska-Wieczorek, A; Ratajczak, J

    2010-05-01

    The complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major chemoattractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the bone marrow (BM). We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal-derived factor-1 (SDF-1)-independent manner because (i) plasma SDF-1 level does not correlate with mobilization efficiency; (ii) the chemotactic plasma gradient is not affected in the presence of AMD3100 and (iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P (i) creates in plasma a continuously present gradient for BM-residing HSPCs; (ii) is at physiologically relevant concentrations a chemoattractant several magnitudes stronger than SDF-1 and (iii) its plasma level increases during mobilization due to CC activation and interaction of the membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.

  10. Gallium scintigraphy in bone infarction. Correlation with bone imaging

    SciTech Connect

    Armas, R.R.; Goldsmith, S.J.

    1984-01-01

    The appearance of gallium-67 images in bone infarction was studied in nine patients with sickle cell disease and correlated with the bone scan findings. Gallium uptake in acute infarction was decreased or absent with a variable bone scan uptake, and normal in healing infarcts, which showed increased uptake on bone scan. The significance of these findings is discussed.

  11. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  12. [Bone mineralization and mineral status].

    PubMed

    Boivin, Georges

    2003-01-01

    After initial calcification in matrix vesicles or collagen fibrils, bones are continually modified by modelling then remodelling. In bone tissue, the degree of mineralisation of bone structural units is heterogeneous, reflects the rate of bone remodelling, and can be measured using microradiography. Our model is based on the fact that bone remodelling activity and thus the duration of the secondary mineralisation of bone tissue would influence its mineral status (mainly its degree of mineralisation or bone density at tissue level). When the bone remodelling rate increases (menopause, parathyroid hormone), the degree of mineralisation of bone tissue decreases. Conversely, after a diminution of the remodelling rate induced by antiresorptive treatments, the degree of mineralisation of bone tissue increases. Strontium ranelate (PROTELOS) has been tested to date as a potential therapeutic agent in patients suffering from postmenopausal osteoporosis. Recent phase III studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] study and the TReatment Of Peripheral Osteoporosis Study [TROPOS]) show a decrease in the vertebral and extravertebral fracture risk and an increase in bone mineral density measured at lumbar spine and femoral levels. Strontium ranelate has a unique mechanism of action, since it decreases bone resorption and increases bone formation ('decoupling' agent). Our preliminary observations in animal and man reveal that, because of this dual mechanism of action, the degree of mineralisation of bone tissue and the crystal characteristics of bone mineral are maintained at normal levels. More generally, these data indicate that the mineral status of bone tissue should be systematically taken into account during histomorphometric studies of bone.

  13. [Bone mineral density in pregnant women from Moscow: possible effects of pregnancy dynamics and nutrient intake].

    PubMed

    Kon, I Ya; Safronova, A I; Gmoshinskaya, M V; Shcheplyagina, L A; Korosteleva, M M; Toboleva, M A; Aleshina, I V; Kurkova, V I; Larionova, Z G

    2014-01-01

    Supporting of bone health is one of the main approaches to provide health in pregnant women considering intensive calcium and other mineral mobilization from mass bone that is necessary forforming fetus bone. This mobilization may lead to decrease of bone mineral density and development of osteopenia and osteoporosis. The important factors of development of bone impairment in pregnancy are nutrition and particular deficient consumption of protein, Ca, vitamin D. The possible role of reduced intake of pregnant women other nutrients remains unexplored. The aim of the research was estimating the prevalence of bone mineral density decrease in regard to the particular course of pregnancy and studying possible effects of key nutrients on bone mineral density in pregnant women. 131 women at different stages of pregnancy were involved in the survey. The bone density assessment was conducted using Bone Densitometer Omnisense 7000. As a criterion for bone density decrease in women used a Z-score, which was considered as normal to -1.0, as reduced from -1.0 to -2,0, and as significantly reduced when Z-score was less than -2,0. Analysis of the actual nutrition was performed by a 24-hour recording of 58 pregnant women. Normal bone mineral density was detected in 54 women or 41% of the total number of women surveyed. In 51 (39%) pregnant women reduced bone mineral density was discovered, and in 26 (20%) patients--significantly reduced bone density. There was a considerable deviation in pregnant patients' diet from the nutrition guidelines, which include, in particular, the high content of fat and saturated fatty acid, reduced intake of some micronutrients such as calcium, zinc, folic acid, β-carotene, vitamins A, B1, E. However, differences in the actual consumption of nutrients in women with varying bone mineral density have been identified only in case of consumption of fat and energy value of diets, also Mn and I. So, it may be suggested that the differences in bone mineral

  14. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

    PubMed Central

    Lieben, Liesbet; Masuyama, Ritsuko; Torrekens, Sophie; Van Looveren, Riet; Schrooten, Jan; Baatsen, Pieter; Lafage-Proust, Marie-Hélène; Dresselaers, Tom; Feng, Jian Q.; Bonewald, Lynda F.; Meyer, Mark B.; Pike, J. Wesley; Bouillon, Roger; Carmeliet, Geert

    2012-01-01

    Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25(OH)2D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25(OH)2D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25(OH)2D not only increases calcium release from bone, but also inhibits calcium incorporation in bone. PMID:22523068

  15. Paget Disease of Bone.

    PubMed

    Al-Rashid, Mamun; Ramkumar, Dipak B; Raskin, Kevin; Schwab, Joseph; Hornicek, Francis J; Lozano-Calderón, Santiago A

    2015-10-01

    The current understanding of Paget disease of bone (PDB) has vastly changed since Paget described the first case in 1877. Medical management of this condition remains the mainstay of treatment. Surgical intervention is usually only used in fractures through pagetic bone, need for realignment to correct deformity in major long bones, prophylactic treatment of impending fractures, joint arthroplasty in severe arthritis, or spinal decompression in cases of bony compression of neural elements. Advances in surgical technique have allowed early return to function and mobilization. Despite medical and surgical intervention, a small subset of patients with PDB develops Paget sarcoma.

  16. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration.

    PubMed

    Agung, Muhammad; Ochi, Mitsuo; Yanada, Shinobu; Adachi, Nobuo; Izuta, Yasunori; Yamasaki, Takuma; Toda, Katsuhiro

    2006-12-01

    The purpose of present study was to evaluate active mobilization effect of mesenchymal stem cells (MSCs) into injured tissues after intraarticular injection of MSCs, and to evaluate their contribution to tissue regeneration. MSCs, which were obtained from green fluorescent protein (GFP) transgenic Sprague-Dawley (SD) rat and cultivated, were injected into normal SD rats in which multiple tissues had been injured including anterior cruciate ligament (ACL), medial meniscus, and articular cartilage of the femoral condyles. At 4 weeks after injection of MSCs, fluorescent microscopic observation, immunohistochemical or histological examinations were performed to evaluate mobilization of MSCs into injured tissue and their contribution to tissue regeneration. In the group of 1 x 10(6) MSCs injection, GFP positive cells could mobilize into the injured ACL alone in all 8 knees. In the group of 1 x 10(7) MSCs injection, GFP positive cells were observed in the injured site of ACL in all 8 knees and in the injured site of medial meniscus and cartilage of femoral condyles in 6 of 8 knees. More interestingly, extracellular matrix stained by toluidine blue was present around GFP positive cells in the injured femoral condyles cartilage and medial meniscus, indicating tissue regeneration. Intraarticularly injected MSCs could mobilize into the injured tissues, and probably contributed to tissue regeneration. This study demonstrated the possibility of intraarticular injection of MSCs for the treatment of intraarticular tissue injuries including ACL, meniscus, or cartilage. If this treatment option is established, it can be minimally invasive compared to conventional surgeries for these tissues.

  17. Cardiomyocyte regeneration from circulating bone marrow cells in mice.

    PubMed

    Kuramochi, Yukio; Fukazawa, Ryuji; Migita, Makoto; Hayakawa, Jun; Hayashida, Mari; Uchikoba, Yohko; Fukumi, Daichi; Shimada, Takashi; Ogawa, Shunichi

    2003-09-01

    We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 +/- 5.9%) and at 3 mo (45.3 +/- 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 +/- 45 cells/50 sections; 3 mo: 458 +/- 100 cells/50 sections; p < 0.05 versus noninfarct, infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

  18. The effect of splinting on tooth mobility. (2) After osseous surgery.

    PubMed

    Galler, C; Selipsky, H; Phillips, C; Ammons, W F

    1979-10-01

    The purpose of this study was to determine if fixed splinting of teeth with intraoral wire and acrylic splints had advantages with respect to tooth mobility, bone level and attachment level over unsplinted teeth following osseous surgery. Ten patients were chosen who exhibited bilaterally similar chronic destructive periodontitis and mobile teeth. One maxillary sextant was splinted, while the other was unsplinted. Both sextants functioned against an unsplinted mandibular arch. Following initial therapy, osseous surgery was performed in both maxillary sextants on the same day. Tooth mobility data was collected 1 week before and at 3, 6, 12, and 24 weeks following surgery. Levels of gingival attachment and bone were recorded before and 24 weeks after surgery. Splints were removed before measurements, then replaced, and the occlusion refined. Prophylaxes and oral hygiene instruction were repeated every 3 weeks throughout the study. For all categories of teeth and mobility examined, tooth mobility increased initially after surgery and subsequently decreased by 24 weeks to about presurgical values. The splinted and unsplinted segments reacted similarly throughout the study; splinting did not significantly reduce the mobility of individual teeth. Pre- and postsurgical bone and gingival attachment levels were also similar for the splinted and unsplinted segments.

  19. [Bone metastases].

    PubMed

    Vicent, S; Luis-Ravelo, D; Antón, I; Hernández, I; Martínez, S; de las Rivas, J; Gúrpide, A; Lecanda, F

    2006-01-01

    Bone metastases represent a devastating clinical problem in the most frequent neoplasies, especially in multiple myeloma, tumours breast, prostate and lung. The consequences include pain which is refractory to conventional analgesics, osteolysis often leading to bone-marrow compression and pathological fractures, and metabolic disorders. Recent advances in diagnosis using imaging techniques as well as different biochemical techniques have helped accurate diagnosis and follow-up. The increase in survival has improved through a multimodal approach combining, inhibition of osteolysis, with prophylactic orthopaedic surgery and radiation therapy. Recent advances in basic research have determined the molecular metastatic that can predict its proclivity to metastasize. Basic research will improve understanding of the basic mechanisms and lead to the clarification of molecular targets that will help in the development of medicines capable of preventing, decreasing or blocking the metastatic process.

  20. Risk Minimization and a Late Holocene Increase in Mobility at Roonka Flat, South Australia: An Analysis of Lower Limb Bone Diaphyseal Shape.

    PubMed

    Hill, Ethan C; Durband, Arthur C; Walshe, Keryn

    2016-09-01

    The strengthening of the El Niño Southern Oscillation (ENSO) in the mid-Holocene caused significant changes in climate, vegetation, and faunal assemblages in South Australia. The appearance of a light, flexible backed-artifact toolkit ∼4 kya has been interpreted as evidence for changes in foraging behavior in response to this event. Optimal foraging theory supports a risk minimization strategy for South Australian hunter-gatherers in which increased mobility was used to cope with effects of a dryer, unstable environment in the late Holocene. Whether this event caused changes in foraging mobility will be tested by examining lower limb external diaphyseal shape between pre-ENSO and post-ENSO skeletons from Roonka Flat, South Australia. Anteroposterior and mediolateral diameters were used to construct diaphyseal shape indices for Roonka Flat femora and tibiae. If populations living in South Australia became more mobile over time, then post-ENSO skeletons should exhibit higher shape indices. The pooled-sex post-ENSO sample has significantly higher femoral shape indices than the pre-ENSO sample. Males do not show significant diaphyseal shape differences over time, but females significantly increase. These data are consistent with the risk minimization model, indicating that South Australians became more mobile post-ENSO to better exploit a less productive environment by expanding their foraging radii. The temporal shift toward more elliptical diaphyses is more notable in females than males, which is consistent with Aboriginal ethnographies that show both sexes being intensely involved in hunting and capturing game animals. Am J Phys Anthropol 161:94-103, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. The mobilization, recruitment and contribution of bone marrow-derived endothelial progenitor cells to the tumor neovascularization occur at an early stage and throughout the entire process of hepatocellular carcinoma growth.

    PubMed

    Zhu, Haitao; Shao, Qianwen; Sun, Xitai; Deng, Zhengming; Yuan, Xianwen; Yu, Decai; Zhou, Xiang; Ding, Yitao

    2012-10-01

    Obvious neovascularization is a key feature of hepatocellular carcinoma (HCC) and the status of neovascularization in HCC is closely correlated with the tumor growth and patient prognosis. The actual effect of current antivascular treatment including embolization to HCC is not satisfactory. Compensatory angiogenesis is one of the primary causes responsible for failure of antiangiogenic therapy. Bone marrow-derived endothelial progenitor cells (BM-EPCs) are considered as important building blocks for adult neovascularization. However, the role of mobilized BM-EPCs in HCC remains unknown. In this study, GFP+-BM orthotropic HCC mice were established to investigate whether BM-EPCs are involved in HCC-induced neovascularization. We found that a large number of BM-EPCs were mobilized into the circulation with the development of HCC, recruited into the HCC region and incorporated into the vascular endothelium directly by differentiation into vascular endothelial cells, including sinus, capillary vessels and great vessels. Dynamic observation revealed that the mobilization and the incorporation of BM-EPCs into different types of vessels were present in early phases and throughout the whole process of HCC growth. The proportion of BM-EPCs in vessels increased gradually, from 17 to 21% with tumor growth. Moreover, injected GFP+-EPCs also specifically homed to tumor tissue and incorporated into tumor vessels directly. In this initial study, we demonstrated that BM-EPCs play a prominent role in HCC neovascularization. Blockade of BM-EPC-mediated vasculogenesis may improve the efficacy of current anti-vascularization therapy for patients with HCC.

  2. A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength.

    PubMed

    Baud'huin, Marc; Solban, Nicolas; Cornwall-Brady, Milton; Sako, Dianne; Kawamoto, Yoshimi; Liharska, Katia; Lath, Darren; Bouxsein, Mary L; Underwood, Kathryn W; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Seehra, Jasbir; Canalis, Ernesto; Pearsall, R Scott; Croucher, Peter I

    2012-07-24

    Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A-mFc) in vivo. mBMPR1A-mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A-mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-κB ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A-mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders.

  3. Bone morphogenetic protein-7 antagonizes tumor necrosis factor-α-induced activation of nuclear factor κB and up-regulation of the ADAMTS, leading to decreased degradation of disc matrix macromolecules aggrecan and collagen II.

    PubMed

    Wang, Zili; Hutton, William C; Yoon, S Tim

    2014-03-01

    Tumor necrosis factor-α (TNF-α) is a regulatory cytokine that can increase the activity of enzymes such as ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which degrade disc matrix. ADAMTS are enzymes that break down disc matrix and thereby mediate disc degeneration. Bone morphogenetic protein-7 (BMP-7), on the other hand, stimulates synthesis of the disc extracellular matrix and is a potential therapeutic molecule for the treatment of disc degeneration. However, the effects of BMP-7 on TNF-α and ADAMTS are unknown. We investigated the effects of BMP-7 on the catabolic regulators such as TNF-α and ADAMTS and evaluated the molecular mechanism by which BMP-7 affects the catabolic regulators. This was an in vitro study in which we used human intervertebral disc cells cultured in alginate beads. Human intervertebral disc cells were cultured in alginate beads, and treated with TNF-α, or TNF- α plus BMP-7, pharmacological inhibitor of ERK1/2 (U0126), p38 (SB203580), or NFκB (BAY 11-7082). The mRNA levels of target genes were measured by real-time polymerase chain reaction, and the protein levels were determined by the Western blots. The nuclear factor (NF)κB activity was analyzed by measured phosphorylation and nuclear translocation of the NFκB protein p65. TNF-α activated NFκB signaling and induced up-regulation of the catabolic regulators ADAMTS-4 and ADAMTS-5, contributing to degradation of the disc matrix macromolecules aggrecan and collagen II. BMP-7 antagonized the TNF-α-induced activation of NFκB protein p65 and blocked TNF-α-induced up-regulation of ADAMTS-4 and ADAMTS-5, leading to reversing TNF-α-mediated degradation of aggrecan and collagen II. Moreover, BMP-7 antagonized the TNF-α-induced activation of NFκB signaling by suppressing phosphorylation and nucleus translocation of NFκB protein p65. BMP-7 antagonizes TNF-α-induced activation of NFκB and up-regulation of ADAMTS, leading to decreased degradation of disc

  4. Ibandronate dose response is associated with increases in bone mineral density and reductions in clinical fractures: results of a meta-analysis.

    PubMed

    Sebba, Anthony I; Emkey, Ronald D; Kohles, Joseph D; Sambrook, Philip N

    2009-03-01

    This meta-analysis pooled data from the four phase III clinical trials of ibandronate to assess the relationship between ibandronate dose, changes in bone mineral density, and rates of both clinical and non-vertebral fractures. Individual patient data from the intent-to-treat population of the BONE, IV fracture prevention, MOBILE, and DIVA studies were included for analysis. The relationship between ibandronate dose and bone mineral density at both the lumbar spine and at the total hip was assessed qualitatively. The relationship between lumbar spine bone mineral density and clinical fracture rate, and the relationship between total hip bone mineral density and non-vertebral fracture rate, were assessed both qualitatively and using mathematical models. A total of 8710 patients were included in this analysis. Both lumbar spine and total hip bone mineral density were observed to increase with increasing ibandronate dose. The incidence of all clinical fractures was observed to decrease as lumbar spine bone mineral density increased. A statistically significant inverse linear relationship was observed between percent change in lumbar spine bone mineral density and the rate of clinical fractures (P=0.005). A non-significant curvilinear relationship was observed between percent change in total hip bone mineral density and non-vertebral fracture rate. Increased ibandronate exposure is associated with increasing gains in the lumbar spine bone mineral density and decreasing clinical fracture rates. A non-linear relationship may exist between increases in the total hip bone mineral density and non-vertebral fracture rate.

  5. Decreased bone mineral density and vertebral compression fractures in a young adult male with 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH): is CAH an unrecognized population at risk for glucocorticoid-induced osteoporosis?

    PubMed

    Loechner, Karen J; Patel, Shipra; Fordham, Lynne; McLaughlin, James T

    2010-01-01

    CAH, most often due to a molecular defect in the 21-OH enzyme, results in inadequate cortisol production and subsequent life-long GC replacement. To heighten awareness for risk of GIO in children with CAH including (1) ongoing assessment of GC dosing, (2) screening for bone health, and (3) prophylactic measures/early intervention once GIO is identified. 23 year-old male with 21OHD CAH referred for osteopenia. Chart review; radiological, serological and urine assessment. Patient has old vertebral compression fractures and diminished BMD, the onset of which likely corresponds to excessive GC dosing during adolescence. As with other GC-dependent conditions, children with CAH may represent a previously unrecognized population at risk for GIO. Physicians need to be cognizant of the consequences of excessive GC dosing on bone health, especially during infancy and adolescence, critical periods for both linear growth as well as bone accretion.

  6. Living Bones, Strong Bones

    NASA Image and Video Library

    In this classroom activity, engineering, nutrition, and physical activity collide when students design and build a healthy bone model of a space explorer which is strong enough to withstand increas...

  7. Calcium regulation and bone mass loss after total gastrectomy in pigs.

    PubMed Central

    Maier, G W; Kreis, M E; Zittel, T T; Becker, H D

    1997-01-01

    OBJECTIVE: Total gastrectomy often results in postgastrectomy bone disease with decreased bone mass and increased fracture risk. To further elucidate the mechanisms of postgastrectomy bone disease, the authors investigated calcium metabolism and bone mineral density after total gastrectomy in pigs. SUMMARY BACKGROUND DATA: Postgastrectomy bone disease can present as osteomalacia, osteoporosis in excess of normal aging, or a combination of both. The underlying mechanisms are insufficiently understood and need further investigation. METHODS: Growing minipigs were gastrectomized and compared with fed-matched, sham-operated control p gs for 1 year. Calcium absorption, serum calcium, parathyroid hormone, 25-(OH)-vitamin D, 1,25-(OH)2-vitamin D, alkaline phosphatase, and computed tomography bone mineral density were measured in three monthly intervals. RESULTS: Total gastrectomy resulted in impaired calcium absorption, reduced serum calcium and 25-(OH)-vitamin D, increased parathyroid hormone and 1,25-(OH)2-vitamin, and reduced bone mineral density compared with fed-matched, sham-operated control pigs. CONCLUSIONS: The authors data indicate that a reduced serum calcium activates counter-regulatory mechanisms, resulting in calcium mobilization from the bone. Possibly, calcium and vitamin D supplementation after total gastrectomy might prevent postgastrectomy bone mass loss. PMID:9065295

  8. Marble Bone Disease: A Rare Bone Disorder

    PubMed Central

    Harinathbabu, Maheswari; Thillaigovindan, Ranjani; Prabhu, Geetha

    2015-01-01

    Osteopetrosis, or marble bone disease, is a rare skeletal disorder due to a defective function of the osteoclasts. This defect renders bones more susceptible to osteomyelitis due to decreased vascularity. This disorder is inherited as autosomal dominant and autosomal recessive. Healthcare professionals should urge these patients to maintain their oral health as well as general health, as this condition makes these patients more susceptible to frequent infections and fractures. This case report emphasizes the signs and symptoms of marble bone disease and presents clinical and radiographic findings.  PMID:26594603

  9. Visualization of bone marrow monocyte mobilization using Cx3cr1gfp/+Flt3L−/− reporter mouse by multiphoton intravital microscopy

    PubMed Central

    Evrard, Maximilien; Chong, Shu Zhen; Devi, Sapna; Chew, Weng Keong; Lee, Bernett; Poidinger, Michael; Ginhoux, Florent; Tan, Suet Mien; Ng, Lai Guan

    2015-01-01

    Monocytes are innate immune cells that play critical roles in inflammation and immune defense. A better comprehension of how monocytes are mobilized and recruited is fundamental to understand their biologic role in disease and steady state. The BM represents a major “checkpoint” for monocyte homeostasis, as it is the primary site for their production and release. Our study determined that the Cx3cr1gfp/+ mouse strain is currently the most ideal model for the visualization of monocyte behavior in the BM by multiphoton intravital microscopy. However, we observed that DCs are also labeled with high levels of GFP and thus, interfere with the accuracy of monocyte tracking in vivo. Hence, we generated a Cx3cr1gfp/+Flt3L−/− reporter mouse and showed that whereas monocyte numbers were not affected, DC numbers were reduced significantly, as DCs but not monocytes depend on Flt3 signaling for their development. We thus verified that mobilization of monocytes from the BM in Cx3cr1gfp/+Flt3L−/− mice is intact in response to LPS. Collectively, our study demonstrates that the Cx3cr1gfp/+Flt3L−/− reporter mouse model represents a powerful tool to visualize monocyte activities in BM and illustrates the potential of a Cx3cr1gfp/+-based, multifunctionality fluorescence reporter approach to dissect monocyte function in vivo. PMID:25516753

  10. Bone Cancer

    MedlinePlus

    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 ...

  11. Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction.

    PubMed

    Archundia, Abel; Aceves, José Luis; López-Hernández, Manuel; Alvarado, Martha; Rodriguez, Emma; Díaz Quiroz, Guillermo; Páez, Araceli; Rojas, Felipe Masso; Montaño, Luis Felipe

    2005-12-05

    Autologous transplant of bone marrow stem cells (BMSC), although extremely useful after acute myocardial events, has not been evaluated in patients with old (>one-year-old) myocardial infarction. Our aim was to determine if CD34(+)-enriched peripheral-blood cells, obtained by apheresis, injected directly into the severely damaged myocardium of five patients with old myocardial infarction could restore depressed myocardial function. We found that 28 weeks after revascularization and peri-infarction injection of the enriched CD34(+) peripheral mononuclear cells, ventricular hemodynamic parameters that included left ventricular ejection fraction, left ventricular diastolic volume, ventricular systolic volume and left ventricular diastolic diameter approximated normal values and there was no restenosis; two patients have been followed for >52 weeks and their parameters are within normal values. In conclusion, intramyocardial injection of easily obtained CD34(+) enriched peripheral blood cells represent an encouraging procedure for patients with severely scarred and dysfunctional myocardium.

  12. Bone disease after renal transplantation

    PubMed Central

    Malluche, Hartmut H.; Monier-Faugere, Marie-Claude; Herberth, Johann

    2015-01-01

    In light of greatly improved long-term patient and graft survival after renal transplantation, improving other clinical outcomes such as risk of fracture and cardiovascular disease is of paramount importance. After renal transplantation, a large percentage of patients lose bone. This loss of bone results from a combination of factors that include pre-existing renal osteodystrophy, immunosuppressive therapy, and the effects of chronically reduced renal function after transplantation. In addition to low bone volume, histological abnormalities include decreased bone turnover and defective mineralization. Low bone volume and low bone turnover were recently shown to be associated with cardiovascular calcifications, highlighting specific challenges for medical therapy and the need to prevent low bone turnover in the pretransplant patient. This Review discusses changes in bone histology and mineral metabolism that are associated with renal transplantation and the effects of these changes on clinical outcomes such as fractures and cardiovascular calcifications. Therapeutic modalities are evaluated based on our understanding of bone histology. PMID:19918255

  13. Duck gait: Relationship to hip angle, bone ash, bone density, and morphology.

    PubMed

    Robison, Cara I; Rice, Meredith; Makagon, Maja M; Karcher, Darrin M

    2015-05-01

    The rapid growth meat birds, including ducks, undergo requires skeletal integrity; however, fast growth may not be conducive to adequate bone structure. A relationship likely exists between skeletal changes and duck mobility. Reduced mobility in meat ducks may have impacts on welfare and production. This study examined the relationships among gait score, bone parameters, and hip angle. Commercial Pekin ducks, ages 14 d (n = 100), 21 d (n = 100), and 32 d (n = 100) were weighed and gait scored with a 3-point gait score system by an observer as they walked over a Tekscan gait analysis system. Gait was scored as GS0, GS1, or GS2 with a score of GS0 defined as good walking ability and a score of GS2 as poorest walking ability. Ducks were humanely euthanized, full body scanned using quantitative computed tomography (QCT), and the right femur and tibia were extracted. Leg bones were cleaned, measured, fat extracted, and ashed. QCT scans were rendered to create computerized 3D models where pelvic hip angles and bone density were measured. Statistical analysis was conducted using PROC MIXED with age and gait score in the model. Body weight increased with age, but within an age, body weight decreased as walking ability became worse (P < 0.01). As expected, linear increases in tibia and femur bone width and length were observed as the ducks aged (P < 0.01). Right and left hip angle increased with duck age (P < 0.01). Additionally, ducks with a GS2 had wider hip angles opposed to ducks with a GS0 (P < 0.01). Bone density increased linearly with both age and gait score (P < 0.05). Femur ash content was lowest in 32-day-old ducks and ducks with GS1 and GS2 (P < 0.0001). Tibia ash content increased with age, but decreased as gait score increased (P < 0.001). The observation that right hip angle changed with gait scores merits further investigation into the relationship between duck mobility and skeletal changes during growth.

  14. Microarchitecture of irradiated bone: comparison with healthy bone

    NASA Astrophysics Data System (ADS)

    Bléry, Pauline; Amouriq, Yves; Guédon, Jeanpierre; Pilet, Paul; Normand, Nicolas; Durand, Nicolas; Espitalier, Florent; Arlicot, Aurore; Malard, Olivier; Weiss, Pierre

    2012-03-01

    The squamous cell carcinomas of the upper aero-digestive tract represent about ten percent of cancers. External radiation therapy leads to esthetic and functional consequences, and to a decrease of the bone mechanical abilities. For these patients, the oral prosthetic rehabilitation, including possibilities of dental implant placement, is difficult. The effects of radiotherapy on bone microarchitecture parameters are not well known. Thus, the purpose of this study is to assess the effects of external radiation on bone micro architecture in an experimental model of 25 rats using micro CT. 15 rats were irradiated on the hind limbs by a single dose of 20 Grays, and 10 rats were non irradiated. Images of irradiated and healthy bone were compared. Bone microarchitecture parameters (including trabecular thickness, trabecular number, trabecular separation, connectivity density and tissue and bone volume) between irradiated and non-irradiated bones were calculated and compared using a Mann and Whitney test. After 7 and 12 weeks, images of irradiated and healthy bone are different. Differences on the irradiated and the healthy bone populations exhibit a statistical significance. Trabecular number, connectivity density and closed porosity are less important on irradiated bone. Trabecular thickness and separation increase for irradiated bone. These parameters indicate a decrease of irradiated bone properties. Finally, the external irradiation induces changes on the bone micro architecture. This knowledge is of prime importance for better oral prosthetic rehabilitation, including implant placement.

  15. Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

    PubMed

    Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

    2017-03-01

    Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Mobile Learning Using Mobile Phones

    ERIC Educational Resources Information Center

    Vicente, Paula

    2013-01-01

    The participation in mobile learning programs is conditioned by having/using mobile communication technology. Those who do not have or use such technology cannot participate in mobile learning programs. This study evaluates who are the most likely participants of mobile learning programs by examining the demographic profile and mobile phone usage…

  17. 2015 Sensorimotor Risk Standing Review Panel Evidence and Status Review For: the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2015-01-01

    The 2015 Sensorimotor Risk Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Human Health Countermeasures (HHC) Element, representatives from the Human Research Program (HRP), NASA Headquarters, and NASA Research and Education Support Services (NRESS) on December 17, 2015 (list of participants is in Section VI of this report). The SRP reviewed the new Evidence Report for the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (from here on referred to as the 2015 Sensorimotor Evidence Report), and also received a status review of the Risk. The opening section of the 2015 Sensorimotor Evidence Report provides written descriptions of various incidents that have occurred during space missions. In most of these incidents, the main underlying contributing factors are not easy to identify unambiguously. For example, in section 1.9, a number of falls occurred while astronauts were walking on the moon. It is not clear to the SRP, however, why they fell. It is only possible to extrapolate from likely specific psychophysical or physiological abnormalities, but how these abnormalities were determined, and how they were directly responsible for the falls is unclear to the SRP. Section 2.1.2 on proprioception is very interesting, but the functional significance of the abnormalities detected is not clear. The SRP sees this as a problem throughout the report: a mapping between the component abnormalities identified and the holistic behaviors that are most relevant, for example, controlling the vehicle, and locomotion during egress, is generally lacking. The SRP thinks the cognitive section is too strongly focused on vestibular functioning. The SRP questions the notion that the main cognitive effects are mainly attributable to reversible vestibular changes induced by spaceflight. The SRP thinks that there can also

  18. Bone remodeling after renal transplantation.

    PubMed

    Bellorin-Font, Ezequiel; Rojas, Eudocia; Carlini, Raul G; Suniaga, Orlando; Weisinger, José R

    2003-06-01

    Several studies have indicated that bone alterations after transplantation are heterogeneous. Short-term studies after transplantation have shown that many patients exhibit a pattern consistent with adynamic bone disease. In contrast, patients with long-term renal transplantation show a more heterogeneous picture. Thus, while adynamic bone disease has also been described in these patients, most studies show decreased bone formation and prolonged mineralization lag-time faced with persisting bone resorption, and even clear evidence of generalized or focal osteomalacia in many patients. Thus, the main alterations in bone remodeling are a decrease in bone formation and mineralization up against persistent bone resorption, suggesting defective osteoblast function, decreased osteoblastogenesis, or increased osteoblast death rates. Indeed, recent studies from our laboratory have demonstrated that there is an early decrease in osteoblast number and surfaces, as well as in reduced bone formation rate and delayed mineralization after transplantation. These alterations are associated with an early increase in osteoblast apoptosis that correlates with low levels of serum phosphorus. These changes were more frequently observed in patients with low turnover bone disease. In contrast, PTH seemed to preserve osteoblast survival. The mechanisms of hypophosphatemia in these patients appear to be independent of PTH, suggesting that other phosphaturic factors may play a role. However, further studies are needed to determine the nature of a phosphaturic factor and its relationship to the alterations of bone remodeling after transplantation.

  19. Is mobilized peripheral blood comparable with bone marrow as a source of hematopoietic stem cells for allogeneic transplantation from HLA-identical sibling donors? A case-control study.

    PubMed

    Gallardo, David; de la Cámara, Rafael; Nieto, Jose B; Espigado, Ildefonso; Iriondo, Arturo; Jiménez-Velasco, Antonio; Vallejo, Carlos; Martín, Carmen; Caballero, Dolores; Brunet, Salut; Serrano, David; Solano, Carlos; Ribera, Josep M; de la Rubia, Javier; Carreras, Enric

    2009-09-01

    Granulocyte colony-stimulating factor mobilized peripheral blood stem cells are increasingly used instead of bone marrow as a stem cell source for transplantation. Whereas this change is almost complete for autologous transplantation, there are some concerns when considering allogeneic transplants. We performed a retrospective case-control study including 820 adult patients who had received an allogeneic stem cell transplant from an HLA-identical sibling donor. Quality of life (QoL) was assessed in 150 patients using the EORTC Quality of Life Questionnaire C30 (QLQ-C30). There were no statistically significant differences in overall survival at ten years (bone marrow: 48.9% vs. peripheral blood stem cells: 39.8%; p=0.621), transplant-related mortality (bone marrow: 28.9% vs. peripheral blood stem cells: 34.4%; p=0.682) or relapse incidence at 9 years (29.4% vs. 35.2%, respectively; p=0.688). Similar outcomes were maintained independently of the phase of the disease. However, multivariate analysis identified a higher incidence of acute graft-versus-host disease grades II-IV (p: 0.023; Hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.05-1.89) and grades III-IV (p: 0.006; HR: 1.89; 95% CI: 1.20-2.98), in the peripheral blood stem cells-stem cell transplant group. As previously described, extensive chronic graft-versus-host disease was also more frequent in the peripheral blood stem cells group (28% vs. 15.6%; p<0.001). Patients transplanted with peripheral blood stem cells had significant impairment of role and social functioning. Although overall survival was not affected by the stem cell source, peripheral blood stem cell transplants were associated with a higher risk of both acute and chronic GvHD. Global quality of life was similar in both groups, but patients transplanted with peripheral blood stem cells showed worse role and social functioning scores, probably related to the increased incidence of chronic graft-versus-host disease.

  20. Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts.

    PubMed

    Park, Min Hee; Lee, Jong Kil; Kim, Namoh; Min, Woo-Kie; Lee, Jeong Eun; Kim, Kyoung-Tae; Akiyama, Haruhiko; Herzog, Herbert; Schuchman, Edward H; Jin, Hee Kyung; Bae, Jae-Sung

    2016-08-01

    Hematopoietic stem/progenitor cell (HSPC) mobilization is an essential homeostatic process regulated by the interaction of cellular and molecular components in bone marrow niches. It has been shown by others that neurotransmitters released from the sympathetic nervous system regulate HSPC egress from bone marrow to peripheral blood. In this study, we investigate the functional role of neuropeptide Y (NPY) on this process. NPY deficient mice had significantly impaired HSPC mobilization due to increased expression of HSPC maintenance factors by reduction of matrix metalloproteinase-9 (MMP-9) activity in bone marrow. Pharmacological or endogenous elevation of NPY led to decrease of HSPC maintenance factors expression by activating MMP-9 in osteoblasts, resulting in HSPC mobilization. Mice in which the Y1 receptor was deleted in osteoblasts did not exhibit HSPC mobilization by NPY. Furthermore, NPY treatment in ovariectomized mice caused reduction of bone loss due to HSPC mobilization. These results suggest a new role of NPY on HSPC mobilization, as well as the potential therapeutic application of this neuropeptide for stem cell-based therapy. Stem Cells 2016;34:2145-2156.

  1. Exercise and bone mass in adults.

    PubMed

    Guadalupe-Grau, Amelia; Fuentes, Teresa; Guerra, Borja; Calbet, Jose A L

    2009-01-01

    decreasing fracture risk. Older men have been less studied than women, and although it seems that men may respond better than their female counterparts, the experimental evidence for a dimorphism based on sex in the osteogenic response to exercise in the elderly is weak. A randomized longitudinal study of the effects of exercise on bone mass in elderly men and women is still lacking. It remains to be determined if elderly females need a different exercise protocol compared with men of similar age. Impact and resistance exercise should be advocated for the prevention of osteoporosis. For those with osteoporosis, weight-bearing exercise in general, and resistance exercise in particular, as tolerated, along with exercise targeted to improve balance, mobility and posture, should be recommended to reduce the likelihood of falling and its associated morbidity and mortality. Additional randomized controlled trials are needed to determine the most efficient training loads depending on age, sex, current bone mass and training history for improvement of bone mass.

  2. Hypercalciuric Bone Disease

    NASA Astrophysics Data System (ADS)

    Favus, Murray J.

    2008-09-01

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

  3. Mobility management in mobile IP

    NASA Astrophysics Data System (ADS)

    Medidi, Sirisha; Golshani, Forouzan

    2002-07-01

    There is an emerging interest in integrating mobile wireless communication with the Internet based on the Ipv6 technology. Many issues introduced by the mobility of users arise when such an integration is attempted. This paper addresses the problem of mobility management, i.e., that of tracking the current IP addresses of mobile terminals and sustaining active IP connections as mobiles move. The paper presents some architectural and mobility management options for integrating wireless access to the Internet. We then present performance results for Mobile IPv4, route optimization and Mobile IPv6.

  4. Bone cells and bone turnover in diabetes mellitus.

    PubMed

    Rubin, Mishaela R

    2015-06-01

    Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due, at least in part, to altered bone remodeling and bone cell function in diabetes. Circulating biochemical markers of bone formation, including P1NP, osteocalcin and bone-specific alkaline phosphatase have been found to be decreased in type 2 diabetes (T2D) and may be predictive of fractures independently of bone mineral density (BMD). These findings have been corroborated by preliminary histomorphometric data. Reductions in the bone resorption marker serum CTx in T2D have also been reported. Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Other factors such as bone marrow fat saturation, advanced glycation endproduct (AGE) accumulation, and microarchitectural changes might also relate to bone cell function and fracture risk in diabetes.

  5. Porous Surface Modified Bioactive Bone Cement for Enhanced Bone Bonding

    PubMed Central

    Huang, Li; Dong, Jingjing; Guo, Dagang; Mao, Mengmeng; Kong, Liang; Li, Yang; Wu, Zixiang; Lei, Wei

    2012-01-01

    Background Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth. Materials and Methods The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant–bone interface was also investigated by push-out tests. Results The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony defect. Conclusions

  6. Bone quality: the determinants of bone strength and fragility.

    PubMed

    Fonseca, Hélder; Moreira-Gonçalves, Daniel; Coriolano, Hans-Joachim Appell; Duarte, José Alberto

    2014-01-01

    Bone fragility is a major health concern, as the increased risk of bone fractures has devastating outcomes in terms of mortality, decreased autonomy, and healthcare costs. Efforts made to address this problem have considerably increased our knowledge about the mechanisms that regulate bone formation and resorption. In particular, we now have a much better understanding of the cellular events that are triggered when bones are mechanically stimulated and how these events can lead to improvements in bone mass. Despite these findings at the molecular level, most exercise intervention studies reveal either no effects or only minor benefits of exercise programs in improving bone mineral density (BMD) in osteoporotic patients. Nevertheless, and despite that BMD is the gold standard for diagnosing osteoporosis, this measure is only able to provide insights regarding the quantity of bone tissue. In this article, we review the complex structure of bone tissue and highlight the concept that its mechanical strength stems from the interaction of several different features. We revisited the available data showing that bone mineralization degree, hydroxyapatite crystal size and heterogeneity, collagen properties, osteocyte density, trabecular and cortical microarchitecture, as well as whole bone geometry, are determinants of bone strength and that each one of these properties may independently contribute to the increased or decreased risk of fracture, even without meaningful changes in aBMD. Based on these findings, we emphasize that while osteoporosis (almost) always causes bone fragility, bone fragility is not always caused just by osteoporosis, as other important variables also play a major role in this etiology. Furthermore, the results of several studies showing compelling data that physical exercise has the potential to improve bone quality and to decrease fracture risk by influencing each one of these determinants are also reviewed. These findings have meaningful clinical

  7. Perspective on the impact of weightlessness on calcium and bone metabolism

    NASA Technical Reports Server (NTRS)

    Holick, M. F.

    1998-01-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  8. Perspective on the impact of weightlessness on calcium and bone metabolism

    NASA Technical Reports Server (NTRS)

    Holick, M. F.

    1998-01-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  9. Osteonectin, bone proteoglycan, and phosphophoryn defects in a form of bovine osteogenesis imperfecta.

    PubMed Central

    Termine, J D; Robey, P G; Fisher, L W; Shimokawa, H; Drum, M A; Conn, K M; Hawkins, G R; Cruz, J B; Thompson, K G

    1984-01-01

    Bovine osteogenesis imperfecta is a congenital disease in Holstein cattle having several characteristics in common with human osteogenesis imperfecta syndromes. In particular, affected calves have multiple bone fractures and friable teeth. Bone collagen isolated from the affected animals (Texas variant) showed slightly decreased alpha 1(I) and alpha 2(I) chain electrophoretic mobility and increased hydroxylysine content. Overall collagen was present in the affected bones at 80-90% of normal values. However, osteonectin, a 32,000 Mr bone-specific protein found previously to promote collagen mineralization in vitro and present in abundance (approximately equal to 3% of total protein) in normal calf bone, was severely depleted (less than 2% of normal levels) in the osteogenesis imperfecta bone and dentin. The bone proteoglycan was similarly depleted. In contrast, the bone sialoprotein was not as severely affected. Further, the diseased teeth lacked (less than 10% of normal values) phosphophoryn, a dentin-specific protein normally present as 4-5% of the total calf dentin matrix. The data suggest multiple hard tissue matrix protein deletions, perhaps due to impaired cell development. Images PMID:6585794

  10. Perspective on the impact of weightlessness on calcium and bone metabolism.

    PubMed

    Holick, M F

    1998-05-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  11. [Vitamin K and bone quality].

    PubMed

    Hara, Kuniko; Akiyama, Yasuhiro

    2007-11-01

    Meta-analysis involving previous clinical studies showed that VK(2) decreased the incidence of fracture. In particular, the results based on the data on bone mineral density and fracture suggested that VK(2) improves bone quality. Preclinical studies regarding bone quality reported that VK(2) improved the trabecular microarchitecture (connectivity and width) in an ovariectomized model, and that VK(2) increased the bone strength without influencing the bone mineral content in a model fed a low-Mg diet and a vitamin C deficiency model, increasing the collagen level and proline hydroxylation. Thus, improvement in bone quality via actions on the bone geometry and collagen level/quality may be involved in a VK(2)-related decrease in the incidence of new fracture in clinical studies.

  12. Longitudinal bone mineral content and density in Rett syndrome and their contributing factors.

    PubMed

    Jefferson, Amanda; Fyfe, Sue; Downs, Jenny; Woodhead, Helen; Jacoby, Peter; Leonard, Helen

    2015-05-01

    Bone mass and density are low in females with Rett syndrome. This study used Dual energy x-ray absorptiometry to measure annual changes in z-scores for areal bone mineral density (aBMD) and bone mineral content (BMC) in the lumbar spine and total body in an Australian Rett syndrome cohort at baseline and then after three to four years. Bone mineral apparent density (BMAD) was calculated in the lumbar spine. Annual changes in lean tissue mass (LTM) and bone area (BA) were also assessed. The effects of age, genotype, mobility, menstrual status and epilepsy diagnosis on these parameters were also investigated. The baseline sample included 97 individuals who were representative of the total live Australian Rett syndrome population under 30years in 2005 (n=274). Of these 74 had a follow-up scan. Less than a quarter of females were able to walk on their own at follow-up. Bone area and LTM z-scores declined over the time between the baseline and follow-up scans. Mean height-standardised z-scores for the bone outcomes were obtained from multiple regression models. The lumbar spine showed a positive mean annual BMAD z-score change (0.08) and a marginal decrease in aBMD (-0.04). The mean z-score change per annum for those 'who could walk unaided' was more positive for LS BMAD (p=0.040). Total body BMD mean annual z-score change from baseline to follow-up was negative (-0.03). However this change was positive in those who had achieved menses prior to the study (0.03, p=0,040). Total body BMC showed the most negative change (-0.60), representing a decrease in bone mineral content over time. This normalised to a z-score change of 0.21 once adjusted for the reduced lean tissue mass mean z-score change (-0.21) and bone area mean z-score change (-0.14). Overall, the bone mineral content, bone mineral density, bone area and lean tissue mass z-scores for all outcome measures declined, with the TB BMC showing significant decreases. Weight, height and muscle mass appear to have

  13. Granulocyte-colony stimulating factor for mobilizing bone marrow stem cells in subacute stroke: the stem cell trial of recovery enhancement after stroke 2 randomized controlled trial.

    PubMed

    England, Timothy J; Abaei, Maryam; Auer, Dorothee P; Lowe, James; Jones, D Rhodri E; Sare, Gillian; Walker, Marion; Bath, Philip M W

    2012-02-01

    Granulocyte-colony stimulating factor (G-CSF) is neuroprotective in experimental stroke and mobilizes CD34(+) peripheral blood stem cells into the circulation. We assessed the safety of G-CSF in recent stroke in a phase IIb single-center randomized, controlled trial. G-CSF (10 μg/kg) or placebo (ratio 2:1) was given SC for 5 days to 60 patients 3 to 30 days after ischemic or hemorrhagic stroke. The primary outcome was the frequency of serious adverse events. Peripheral blood counts, CD34(+) count, and functional outcome were measured. MRI assessed lesion volume, atrophy, and the presence of iron-labeled CD34(+) cells reinjected on day 6. Sixty patients were recruited at mean of 8 days (SD ± 5) post ictus, with mean age 71 years (± 12 years) and 53% men. The groups were well matched for baseline minimization/prognostic factors. There were no significant differences between groups in the number of participants with serious adverse events: G-CSF 15 (37.5%) of 40 versus placebo 7 (35%) of 20, death or dependency (modified Rankin Score: G-CSF 3.3 ± 1.3, placebo 3.0 ± 1.3) at 90 days, or the number of injections received. G-CSF increased CD34(+) and total white cell counts of 9.5- and 4.2-fold, respectively. There was a trend toward reduction in MRI ischemic lesion volume with respect to change from baseline in G-CSF-treated patients (P=0.06). In 1 participant, there was suggestion that labeled CD34(+) cells had migrated to the ischemic lesion. This randomized, double-blind, placebo-controlled trial suggests that G-CSF is safe when administered subacutely. It is feasible to label and readminister iron-labeled CD34(+) cells in patients with ischemic stroke. URL: www.controlled-trials.com. Unique identifier: ISRCTN63336619.

  14. Bone marrow aspiration

    MedlinePlus

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

  15. To Be Connected or Not To Be Connected? Mobile Messenger Overload, Fatigue, and Mobile Shunning.

    PubMed

    Shin, Jaewook; Shin, Mincheol

    2016-10-01

    With the increased adoption of mobile devices, mobile communication is all around us and we are connected anywhere, anytime. Mobile communication in general and mobile messenger service in particular make interpersonal communication in Korea so frequent and convenient. However, being connected too much anywhere and anytime via mobile messenger service appears to lead an increasing number of people to feel fatigue and to decrease mobile communication under some conditions. Based on a sample of 334 respondents, this study empirically investigated the relationships among commercial, noncommercial mobile messenger overload, mobile messenger fatigue, relational self-concept, and mobile shunning behavior. The findings show that (a) the effect of noncommercial mobile messenger overload is stronger than that of commercial mobile messenger overload in increasing mobile messenger fatigue although both positively affect mobile messenger fatigue, (b) relational self-concept has moderating effects on the relationship between mobile messenger overload and mobile messenger fatigue, and that (c) mobile messenger fatigue triggers mobile communicators' shunning behavior through which the communicators increase their intention to avoid mobile communication, to change their mobile phone numbers, and to subscribe to dual number service on one mobile device. When confronted with mobile messenger fatigue caused by mobile messenger overload, mobile messaging service users are likely to shun their mobile communication. Being constantly and conveniently connected appears to be a blessing in disguise.

  16. Bone impairment in oxalosis: An ultrastructural bone analysis.

    PubMed

    Bacchetta, Justine; Farlay, Delphine; Abelin-Genevois, Kariman; Lebourg, Ludivine; Cochat, Pierre; Boivin, Georges

    2015-12-01

    Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of systemic oxalosis. Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains and specific oxalate osteopathy on plain X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction due to an invasion of bone surface by macrophages. We present data obtained in 10 samples from 8 patients with oxalosis (16-68 years) who underwent iliac crest bone biopsy and bone quality analysis using modern methods (microradiography, microindentation, Fourier Transform InfraRed Microspectroscopy, transmission electron microscopy) in addition to histomorphometry. Disseminated calcium oxalate deposits (whewellite) were found in the bone marrow space (with a granulomatous reaction) but not in the bone matrix. Calcium oxalate deposits were totally surrounded by macrophages and multinucleated giant cells, and a phagocytosis activity was sometimes observed. Very few calcium oxalate crystals were directly in close contact with the mineral substance of the bone. Bone mineralization was not modified by the presence of calcium oxalate even in close vicinity. Bone quality analysis also revealed a harder bone than normal, perhaps in relationship with decreased carbonate content in the mineral. This increase in bone hardness could explain a more "brittle" bone. In patients with oxalosis, the formation and growth of calcium oxalate crystals in the bone appeared independent of apatite. The mechanisms leading to nucleation and growth of oxalate deposits are still unclear and deserve further studies.

  17. Bone mineral density and functional measures in patients with arthrogryposis.

    PubMed

    Spencer, Hillard T; Bowen, Richard E; Caputo, Kimberly; Green, Terri A; Lawrence, John F

    2010-01-01

    Patients with arthrogryposis often report decreased ambulation and physical activity. Given that skeletal mineralisation is responsive to force, we identified the need to characterize bone mineral density and functional measures in this population, and conducted a cross-sectional study to establish a reference for future investigations. Thirty consecutive patients aged 5 to 18 years with either the diagnosis of amyoplasia or nonsyndromic arthrogryposis with predominantly lower extremity involvement underwent bone densitometry testing, and lumbar spine Z-scores were calculated against an age and sex-matched control population as is customary in children. Pediatric outcomes data collection instrument (PODCI) and functional independence measure for Children (WeeFIM) assessment forms were completed. Mean Z-scores, PODCI, and WeeFIM scores were calculated. Statistical analysis was performed to compare lumbar spine Z-scores between patients divided by ambulatory status and to correlate WeeFIM and PODCI scores. Mean lumbar spine Z-score was -0.47, with 73% of Z-scores being <0. Mean Z-score among nonambulators or home ambulators was -1.05, as compared to a mean Z-score among limited and unlimited community ambulators of -0.14 with a trend toward significance (P=0.10), and a dose-response relationship between higher bone density and increasing ambulatory function. Mean WeeFIM self-care and mobility quotient scores were 67.5/100 and 70.9/100, respectively. PODCI normative scores were decreased for upper extremity (10/50), transfer/basic mobility (-17/50), and sports/physical function (4/50), but normal in pain/comfort (45/50) and happiness (49/50). A linear relationship was noted between functional ambulation level and WeeFIM quotient and PODCI normative scores. There was good correlation between WeeFIM mobility and PODCI transfers and basic mobility standardised scores (R=0.86). This is the first study to measure bone mineral density in children with arthrogryposis, and

  18. [The effect of a decrease in the mobilization of Ca+ and its chemo-controlled intake into the cytoplasm on the modulation of cholinoreceptor neuronal plasticity in Helix lucorum snails by 15-hydroxyeicosatetraenoic acid].

    PubMed

    Pivovarov, A S; Egido-Villareal, W

    1993-11-01

    The effects of extracellular solution without Ca2+ and inhibitors of Ca2+ mobilization dependent of Ca2+ (tetracaine) and inositol-1,4,5-trisphosphate (TMB-8) on the modulation of cholinoreceptor (ChR) plasticity of identified Helix lucorum RPa3 and LPa3 neurons by 15(S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (15-HETE) were investigated. Using the double-electrode voltage-clamp technique, the inward current, induced by local ionophoretic acetylcholine application (ACh-current), was recorded. ChR plasticity was evaluated by extinction of ACh-current developed in a process of rhythmic ACh applications on the soma with an interval 60-240 s. Tetracaine and TMB-8 disturbed long-latent modulatory effect of 15-HETE and did not influence short-latent one. Extraction of Ca2+ from extracellular solution did not affect the modulatory effect of 15-HETE. It was concluded that one of the molecular mechanisms of ChR plasticity deepening due 15-HETE (in long-latent phase) induces potentiation of Ca(2+)- and inositol-1,4,5-trisphosphate-dependent Ca2+ mobilization evoked by 5-lipoxygenase eicosanoids.

  19. Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases.

    PubMed

    Zhang, Qian; Chen, Bin; Yan, Fuhua; Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

  20. Interleukin-10 Inhibits Bone Resorption: A Potential Therapeutic Strategy in Periodontitis and Other Bone Loss Diseases

    PubMed Central

    Guo, Jianbin; Zhu, Xiaofeng; Ma, Shouzhi; Yang, Wenrong

    2014-01-01

    Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy. PMID:24696846

  1. Similar survival following HLA-identical sibling transplantation for standard indication in children with haematologic malignancies: a single center comparison of mobilized peripheral blood stem cell with bone marrow transplantation.

    PubMed

    Meisel, R; Enczmann, J; Balzer, S; Bernbeck, B; Kramm, C; Schönberger, S; Sinha, K; Tröger, A; Wernet, P; Göbel, U; Laws, H J; Dilloo, D

    2005-01-01

    Peripheral blood stem cell (PBSC) grafts are increasingly used for autologous and allogeneic haematopoietic stem cell transplantation (alloHSCT) with the aim to hasten neutrophil and platelet engraftment and thereby to reduce transplant-related complications due to infections, bleeding and graft failure. Based on the paucity of data on PBSC transplantation in children we performed a retrospective single-center analysis comparing the outcome of children receiving mobilized PBSC from human leukocyte antigen (HLA)-identical sibling donors to bone marrow (BM) transplant recipients. Between 1996 and 2004, 16 children with haematologic malignancies and standard indication for alloHSCT underwent PBSC transplantation from HLA-identical sibling donors. The outcome of these children was compared to a historic control group of 19 bone marrow (BM) transplant recipients. Time to neutrophil engraftment, incidence of acute and chronic graft-versus-host disease (GvHD), relapse rate, transplant-related mortality, event-free and overall survival were analyzed. Neutrophil engraftment was achieved significantly faster after PBSC compared to BM transplantation with a median time to neutrophil engraftment of 11 (range: 8-21) and 19 (16-44) days for the PBSC and BM cohort, respectively (p < 0.001). Two of 19 (11 %) BM recipients did not achieve primary neutrophil engraftment and both patients died due to infectious complications. The rate of clinically significant acute GvHD > or = grade II was higher in the PBSC compared to the BM group (75 vs. 39 %; p = 0.045). Incidences of chronic GvHD (PBSC vs. BM: 60 vs. 44 %), death of disease (13 vs. 21 %) and death of complication (13 vs. 16 %) were comparable between both groups (p = ns). With a median follow up of 4.7 years (PBSC) and 10.2 years (BM) overall survival (PBSC vs. BM: 68.6 +/- 13.5 vs. 63.2 +/- 11.1 %; p = 0.65) and event-free survival (67.0 +/- 12.1 vs. 63.2 +/- 11.1 %; p = 0.80) is without demonstrable difference in both groups

  2. Peripheral Leptin Regulates Bone Formation

    PubMed Central

    Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

    2012-01-01

    Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

  3. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    PubMed

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria.

  4. [Vitamin D metabolism of the bone].

    PubMed

    Barvencik, F; Amling, M

    2015-09-01

    Bone health is a crucial requirement for individual mobility. Preventive, diagnostic, and therapeutic actions to preserve or restore bone health are major tasks for orthopedic surgeons and health practitioners in musculoskeletal medicine. In the context of the widespread vitamin D deficiency in Germany, it is relevant to keep in mind thatserum calcitriol levels above > 30 µg/l are necessary for optimal bone metabolism and bone health. In particular, because vitamin D deficiency not only increases the amount of non-mineralized bone matrix (osteoid), but it can also cause negative changes in the mineralized bone tissue. Widening of the osteons and osteocyte lacunae, together with increased bone aging under the osteoid layer, can lead to reduced fracture resistance. Integration of bone metabolism into the orthopedic strategy is an important concept for optimizing treatment in modern musculoskeletal medicine.

  5. Bone tumor

    MedlinePlus

    ... primary bone tumors include: Chondrosarcoma Ewing sarcoma Fibrosarcoma Osteosarcomas Cancers that most often spread to the bone are cancers of the: Breast Kidney Lung Prostate Thyroid These forms of cancer usually affect ...

  6. Bone grafts.

    PubMed

    Hubble, Matthew J W

    2002-09-01

    Bone grafts are used in musculoskeletal surgery to restore structural integrity and enhance osteogenic potential. The demand for bone graft for skeletal reconstruction in bone tumor, revision arthroplasty, and trauma surgery, couple with recent advances in understanding and application of the biology of bone transplantation, has resulted in an exponential increase in the number of bone-grafting procedures performed over the last decade. It is estimated that 1.5 million bone-grafting procedures are currently performed worldwide each year, compared to a fraction of that number 20 years ago. Major developments also have resulted in the harvesting, storage, and use of bone grafts and production of graft derivatives, substitutes, and bone-inducing agents.

  7. Bone Analyzer

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The danger of disuse osteoporosis under weightless condition in space led to extensive research into measurements of bone stiffness and mass by the Biomedical Research Division of Ames and Stanford University. Through its Technology Utilization Program, NASA funded an advanced SOBSA, a microprocessor-controlled bone probe system. SOBSA determines bone stiffness by measuring responses to an electromagnetic shaker. With this information, a physician can identify bone disease, measure deterioration and prescribe necessary therapy. The system is now undergoing further testing.

  8. Multiscale imaging of bone microdamage

    PubMed Central

    Poundarik, Atharva A.; Vashishth, Deepak

    2015-01-01

    Bone is a structural and hierarchical composite that exhibits remarkable ability to sustain complex mechanical loading and resist fracture. Bone quality encompasses various attributes of bone matrix from the quality of its material components (type-I collagen, mineral and non-collagenous matrix proteins) and cancellous microarchitecture, to the nature and extent of bone microdamage. Microdamage, produced during loading, manifests in multiple forms across the scales of hierarchy in bone and functions to dissipate energy and avert fracture. Microdamage formation is a key determinant of bone quality, and through a range of biological and physical mechanisms, accumulates with age and disease. Accumulated microdamage in bone decreases bone strength and increases bone’s propensity to fracture. Thus, a thorough assessment of microdamage, across the hierarchical levels of bone, is crucial to better understand bone quality and bone fracture. This review article details multiple imaging modalities that have been used to study and characterize microdamage; from bulk staining techniques originally developed by Harold Frost to assess linear microcracks, to atomic force microscopy, a modality that revealed mechanistic insights into the formation diffuse damage at the ultrastructural level in bone. New automated techniques using imaging modalities such as microcomputed tomography are also presented for a comprehensive overview. PMID:25664772

  9. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    PubMed

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  10. Bone Infections

    MedlinePlus

    ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent injury to the bone. You may also be at risk if you are having hemodialysis. Symptoms of bone infections include Pain in the infected area Chills and ...

  11. Recruitment of bone marrow-derived cells to periodontal tissue defects

    PubMed Central

    Kimura, Yasuyuki; Komaki, Motohiro; Iwasaki, Kengo; Sata, Masataka; Izumi, Yuichi; Morita, Ikuo

    2014-01-01

    Bone marrow-derived cells (BMCs) are considered to be a major source of mesenchymal stem cells (MSCs) in adults and are known to be effective in periodontal tissue regeneration. However, whether endogenous BMCs are involved in periodontal tissue repair process is uncertain. We therefore created periodontal tissue defects in the buccal alveolar bone of mandibular first molars in bone marrow chimeric mice, and immunohistochemically examined the expression of stromal cell derived factor-1 (SDF-1) and the mobilization of BMCs. We found that SDF-1 expression was increased around the defects at as early as 1 week after injury and that BMCs were mobilized to the defects, while GFP+/CD45+ were rarely observed. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the number of platelet-derived growth factor receptor (pdgfr) α+/Sca-1+ (PαS) cells in the bone marrow decreased after injury. Taken together, these results suggest that BMCs are mobilized to the periodontal tissue defects. Recruitment of BMCs, including a subset of MSCs could be a new target of periodontal treatment. PMID:25364726

  12. [Bone lesion in multiple myeloma].

    PubMed

    Ise, Mikiko; Takagi, Toshiyuki

    2007-12-01

    Bone destruction is a hallmark of multiple myeloma(MM). Almost all MM patients develop osteolytic bone lesions that can cause pathologic fractures and severe bone pain. Osteolytic lesions result from increased bone resorption due to osteoclast stimulation and decreased bone formation due to osteoblast inhibition. Plain radiography, CT, and MRI are established imaging techniques in MM. FDG-PET imaging is promising newer scanning technique under current evaluation. The aggressive features of MM bone lesions have significantly contributed to poor prognosis. Therefore, a systemic approach to analgesia, which includes radiotherapy and orthopedic intervention, must be applied as a part of the comprehensive care plan of MM patient. Bisphosphonates have been shown to reduce vertebral fractures and bone pain.

  13. Bone Metabolism in Anorexia Nervosa

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  14. TARGETING POLYMER THERAPEUTICS TO BONE

    PubMed Central

    Low, Stewart; Kopeček, Jindřich

    2012-01-01

    An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

  15. [Basics of Pauwels' theory of the functional adaptation of bones].

    PubMed

    Kummer, B

    1995-09-01

    Bone is a secondary support tissue. It develops on the base of a preexistent primary scaffold, built up by connective tissue or by cartilage. Bone formation depends on the magnitude of the elastic deformation, due to loading. The skeletal organ "bone" reacts to the actual stress like a feedback system: high stress stimulates new bone formation and incorporation of mineral salts; low stress leads to bone resorption and mobilization of mineral salts. The result of extreme stress is bone resorption (stress fractures, pseudocysts). The radiological density and architecture of the spongy bone reflect exactly the direction and local magnitude of stress.

  16. Changes in bone mineral status and bone size during pregnancy and the influences of body weight and calcium intake.

    PubMed

    Olausson, Hanna; Laskey, M Ann; Goldberg, Gail R; Prentice, Ann

    2008-10-01

    Calcium may be mobilized from the maternal skeleton during pregnancy, which may be influenced by several factors. The objective was to investigate changes in bone mineral status and size during pregnancy and to consider the influences of body weight and calcium intake. Thirty-four British women were studied before pregnancy and 2 wk postpartum (Preg). Eighty-four nonpregnant, nonlactating (NPNL) women were studied over a corresponding time. Bone mineral content (BMC), bone area (BA), areal bone mineral density (aBMD), and BA-adjusted BMC of the whole-body, lumbar spine, radius, and hip were measured by dual-energy X-ray absorptiometry. The Preg group experienced significant decreases in BMC, aBMD, and BA-adjusted BMC at the whole-body, spine, and total hip of between 1% and 4%. Whole-body BMC increased in the NPNL group, and aBMD and BA-adjusted BMC decreased at the spine and hip by 0.5% to 1%. Whole-body BMC decreased in the Preg group by -2.16 +/- 0.46%, equivalent to -2.71 +/- 0.43% relative to the NPNL group (P < or = 0.001). Weight change was a positive predictor of skeletal change at the spine, hip, and radius in both groups. Differences between the Preg and NPNL groups in change in BA-adjusted BMC, after correction for weight change and other influences, were as follows (P < or = 0.01): whole-body, -1.70 +/- 0.25%; spine, -3.03 +/- 0.72%; and total hip, -1.87 +/- 0.60%. Calcium intake was not a significant predictor of skeletal change in either group. Pregnancy is associated with decreases in whole-body and regional bone mineral status sufficient to make a sizeable contribution to maternal and fetal calcium economy. Calcium intake is not a significant predictor of the skeletal response to pregnancy in well-nourished women.

  17. Bone Densitometry (Bone Density Scan)

    MedlinePlus

    ... In some communities, a CT scan with special software can also be used to diagnose or monitor ... patient's bone mineral density. DEXA machines feature special software that compute and display the bone density measurements ...

  18. Predicting bone remodeling around tissue- and bone-level dental implants used in reduced bone width.

    PubMed

    Eser, Atilim; Tonuk, Ergin; Akca, Kivanc; Dard, Michel M; Cehreli, Murat Cavit

    2013-09-03

    The objective of this study was to predict time-dependent bone remodeling around tissue- and bone-level dental implants used in patients with reduced bone width. The remodeling of bone around titanium tissue-level, and titanium and titanium-zirconium alloy bone-level implants was studied under 100 N oblique load for one month by implementing the Stanford theory into three-dimensional finite element models. Maximum principal stress, minimum principal stress, and strain energy density in peri-implant bone and displacement in x- and y- axes of the implant were evaluated. Maximum and minimum principal stresses around tissue-level implant were higher than bone-level implants and both bone-level implants experienced comparable stresses. Total strain energy density in bone around titanium implants slightly decreased during the first two weeks of loading followed by a recovery, and the titanium-zirconium implant showed minor changes in the axial plane. Total strain energy density changes in the loading and contralateral sides were higher in tissue-level implant than other implants in the cortical bone at the horizontal plane. The displacement values of the implants were almost constant over time. Tissue-level implants were associated with higher stresses than bone-level implants. The time-dependent biomechanical outcome of titanium-zirconium alloy bone-level implant was comparable to the titanium implant. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Long-term therapy in COPD: any evidence of adverse effect on bone?

    PubMed Central

    Langhammer, Arnulf; Forsmo, Siri; Syversen, Unni

    2009-01-01

    Patients with COPD have high risk for osteoporosis and fractures. Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function. This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients. A review of the English-language literature was conducted using the MEDLINE database until June 2009. Currently used bronchodilators probably lack adverse effect on bone. Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry. Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk. This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS. The life-style factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses. The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis. PMID:19888355

  20. Hyperoxia, Endothelial Progenitor Cell Mobilization, and Diabetic Wound Healing

    PubMed Central

    Liu, Zhao-Jun

    2008-01-01

    Abstract Diabetic foot disease is a major health problem, which affects 15% of the 200 million patients with diabetes worldwide. Diminished peripheral blood flow and decreased local neovascularization are critical factors that contribute to the delayed or nonhealing wounds in these patients. The correction of impaired local angiogenesis may be a key component in developing therapeutic protocols for treating chronic wounds of the lower extremity and diabetic foot ulcers. Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal neovascularization and play a central role in wound healing, but their circulating and wound-level numbers are decreased in diabetes, implicating an abnormality in EPC mobilization and homing mechanisms. The deficiency in EPC mobilization is presumably due to impairment of eNOS-NO cascade in bone marrow (BM). Hyperoxia, induced by a clinically relevant hyperbaric oxygen therapy (HBO) protocol, can significantly enhance the mobilization of EPCs from the BM into peripheral blood. However, increased circulating EPCs failed to reach to wound tissues. This is partly a result of downregulated production of SDF-1α in local wound lesions with diabetes. Administration of exogenous SDF-1α into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, neovascularization, and wound healing. Antioxid. Redox Signal. 10, 1869–1882. PMID:18627349

  1. Bone poroelasticity.

    PubMed

    Cowin, S C

    1999-03-01

    Poroelasticity is a well-developed theory for the interaction of fluid and solid phases of a fluid-saturated porous medium. It is widely used in geomechanics and has been applied to bone by many authors in the last 30 years. The purpose of this work is, first, to review the literature related to the application of poroelasticity to the interstitial bone fluid and, second, to describe the specific physical and modeling considerations that establish poroelasticity as an effective and useful model for deformation-driven bone fluid movement in bone tissue. The application of poroelasticity to bone differs from its application to soft tissues in two important ways. First, the deformations of bone are small while those of soft tissues are generally large. Second, the bulk modulus of the mineralized bone matrix is about six times stiffer than that of the fluid in the pores while the bulk moduli of the soft tissue matrix and the pore water are almost the same. Poroelasticity and electrokinetics can be used to explain strain-generated potentials in wet bone. It is noted that strain-generated potentials can be used as an effective tool in the experimental study of local bone fluid flow, and that the knowledge of this technique will contribute to the answers of a number of questions concerning bone mineralization, osteocyte nutrition and the bone mechanosensory system.

  2. New agents in HSC mobilization.

    PubMed

    Domingues, Mélanie J; Nilsson, Susan K; Cao, Benjamin

    2017-02-01

    Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions. AMD3100 (plerixafor), a small molecule that selectively inhibits the chemokine receptor CXCR4 is approved for mobilization in combination with G-CSF in patients with Non-Hodgkin's lymphoma and multiple myeloma. Nevertheless, identifying mobilization strategies that not only enhance HSC number, but are rapid and generate an optimal "mobilized product" for improved transplant outcomes remains an area of clinical importance. In recent times, new agents based on recombinant proteins, peptides and small molecules have been identified as potential candidates for therapeutic HSC mobilization. In this review, we describe the most recent developments in HSC mobilization agents and their potential impact in HSC transplantation.

  3. [Bone substitutes].

    PubMed

    Jordana, Fabienne; Le Visage, Catherine; Weiss, Pierre

    2017-01-01

    Bone substitutes, used to fill a defect after a surgery or a trauma, provide a mechanical support and might induce bone healing. They constitute an alternative to autogenous bone grafts, the 'gold standard' which remains the reference despite its risk of postoperative complications. The clinician choice of a bone substitute is based on the required bone volume, the handling (injectability, malleability) and mechanical properties (setting time, viscosity, resorbability among others) of the material. Bone substitutes are commonly used in orthopedic surgery, neurosurgery, stomatology and dental applications. Their use increases steadily, with the recent clinical development of injectable forms. In addition, novel technologies by subtractive or additive techniques allow today the production of controlled architecture materials. Here, we present a bone substitutes classification according to their origin (natural or synthetic) and chemical composition, and the most common use of these substitutes. © 2017 médecine/sciences – Inserm.

  4. Malignant lymphoma of bone.

    PubMed

    Dürr, Hans Roland; Müller, Peter Ernst; Hiller, Erhard; Maier, Markus; Baur, Andrea; Jansson, Volkmar; Refior, Hans Jürgen

    2002-02-01

    Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed because of unspecific clinical signs and equivocal radiographs. Therapy in general is multimodal, including surgery and radio- and chemotherapy. Our objective was to demonstrate the clinical and radiological aspects of the lesion to optimize diagnostic approaches and to evaluate treatment and prognostic factors. Thirty-six patients with malignant lymphoma of bone who were surgically treated over a 15-year-period were retrospectively reviewed. Seventeen of them showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease with multiple bone or visceral involvement was apparent (dNHL). Six patients suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment was indicated for diagnostic reasons or complications due to the disease. Radiation and chemotherapy were part of the oncological treatment. The patients' mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients was pain, with an average duration of 8 months. In the secondary cases, bone involvement appeared on average 57 months after the initial diagnosis. An osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic sign associated with this disease. The 5-year survival rate was 61% (PLB 88%, dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant factor in the prognosis. Extraskeletal involvement significantly decreased survival. No correlation was found between gender, age, location, or histological subtypes and survival. Bone involvement in NHL appears late in the extraskeletal disease. The clinical appearance is nonspecific, and the delay between the onset of symptoms and diagnosis is often long. One of the major radiologic signs is the existence of a soft-tissue tumor

  5. Targeted disruption of TGFBI in mice reveals its role in regulating bone mass and bone size through periosteal bone formation.

    PubMed

    Yu, Hongrun; Wergedal, Jon E; Zhao, Yongliang; Mohan, Subburaman

    2012-07-01

    Transforming growth factor-beta induced (TGFBI) and periostin are two closely related proteins in structure as well as in function. A previous study found that periostin positively regulates bone size. Here, we hypothesize that TGFBI has a similar function in bone development. To test this hypothesis, we employed TGFBI-deficient mice, which were generated by targeted disruption of the TGFBI gene. We bred these mice with C57BL/6J mice to generate homozygous TGFBI-deficient (TGFBI(-/-)) mice and homozygous wild-type littermates. All mice were raised to 12 weeks of age. Bone mass parameters were determined by PIXImus and micro-CT, bone strength parameters by three-point bending, and bone formation and resorption parameters by histomorphometry. We found that targeted disruption of TGFBI led to reduced body size, bone mass, bone size, and bone strength. This indicates that, like periostin, TGFBI also positively regulates bone size and that changes in bone size affect bone strength. Furthermore, there was also a significant decrease in periosteal, but not endosteal, bone formation rate of cortical bone in TGFBI(-/-) mice, suggesting that the observed effect of TGFBI on bone mass and bone size was largely caused by the effect of TGFBI on periosteal bone formation.

  6. Estimation of In vivo Cancellous Bone Elasticity

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

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

  7. Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats

    PubMed Central

    2012-01-01

    Background Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling. PMID:22443362

  8. Reversal of Bone Marrow Mobilopathy and Enhanced Vascular Repair by Angiotensin-(1-7) in Diabetes.

    PubMed

    Vasam, Goutham; Joshi, Shrinidh; Thatcher, Sean E; Bartelmez, Stephen H; Cassis, Lisa A; Jarajapu, Yagna P R

    2017-02-01

    The angiotensin (ANG)-(1-7)/Mas receptor (MasR) pathway activates vascular repair-relevant functions of bone marrow progenitor cells. We tested the effects of ANG-(1-7) on mobilization and vasoreparative functions of progenitor cells that are impaired in diabetes. The study was performed in streptozotocin-induced diabetic (db/db) mice. Diabetes resulted in a decreased number of Lineage(-)Sca-1(+)c-Kit(+) (LSK) cells in the circulation, which was normalized by ANG-(1-7). Diabetes-induced depletion of LSK cells in the bone marrow was reversed by ANG-(1-7). ρ-Kinase (ROCK) activity was increased specifically in bone marrow LSK cells by ANG-(1-7) in diabetes, and the beneficial effects of ANG-(1-7) were prevented by fasudil. ANG-(1-7) increased Slit3 levels in the bone marrow supernatants, which activated ROCK in LSK cells and sensitized them for stromal-derived factor-1α (SDF)-induced migration. Diabetes prevented the mobilization of LSK cells in response to ischemia and impaired the recovery of blood flow, both of which were reversed by ANG-(1-7) in both models of diabetes. Genetic ablation of MasR prevented ischemia-induced mobilization of LSK cells and impaired blood flow recovery, which was associated with decreased proliferation and migration of LSK cells in response to SDF or vascular endothelial growth factor. These results suggest that MasR is a promising target for the treatment of diabetic bone marrow mobilopathy and vascular disease.

  9. Secondary alveolar bone grafting: our experience with olecranon bone graft.

    PubMed

    Nadal, Emmanuela; Sabás, Mariana; Dogliotti, Pedro; Espósito, Raquel

    2010-03-01

    Management of alveolar cleft has dramatically changed during the last century: secondary alveolar bone grafting is now an integral part of cleft palate and craniofacial center's protocols. The objectives of alveolar repair and bone grafting are as follows: providing a continuous and stable maxillary dental arch, closure of oronasal fistulae, adequate bone for tooth eruption or orthodontic movement, and nasal base support, improving facial aesthetic. Although cancellous iliac bone is the donor site selected more frequently, bone grafts harvested from different sites have been advocated to decrease donor site morbidity.The aim of this study was to propose and evaluate the use of olecranon as a donor site in 24 patients with secondary alveolar cleft. The graft is taken as a single piece to fit the alveolar cleft defect, and it includes periosteum and corticocancellous bone to improve early vascularization and greater volume maintenance.

  10. The controversy of cranial bone motion.

    PubMed

    Rogers, J S; Witt, P L

    1997-08-01

    Cranial bone motion continues to stimulate controversy. This controversy affects the general acceptance of some intervention methods used by physical therapists, namely, cranial osteopathic and craniosacral therapy techniques. Core to these intervention techniques is the belief that cranial bone mobility provides a compliant system where somatic dysfunction can occur and therapeutic techniques can be applied. Diversity of opinion over the truth of this concept characterizes differing viewpoints on the anatomy and physiology of the cranial complex. Literature on cranial bone motion was reviewed for the purpose of better understanding this topic. Published research overall was scant and inconclusive. Animal and human studies demonstrate a potential for small magnitude motion. Physical therapists should carefully scrutinize the literature presented as evidence for cranial bone motion. Further research is needed to resolve this controversy. Outcomes research, however, is needed to validate cranial bone mobilization as an effective treatment.

  11. Bone cutting.

    PubMed

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

    1991-02-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  13. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration.

    PubMed

    Colnot, Céline

    2009-02-01

    Bone repair requires the mobilization of adult skeletal stem cells/progenitors to allow deposition of cartilage and bone at the injury site. These stem cells/progenitors are believed to come from multiple sources including the bone marrow and the periosteum. The goal of this study was to establish the cellular contributions of bone marrow and periosteum to bone healing in vivo and to assess the effect of the tissue environment on cell differentiation within bone marrow and periosteum. Results show that periosteal injuries heal by endochondral ossification, whereas bone marrow injuries heal by intramembranous ossification, indicating that distinct cellular responses occur within these tissues during repair. [corrected] Next, lineage analyses were used to track the fate of cells derived from periosteum, bone marrow, and endosteum, a subcompartment of the bone marrow. Skeletal progenitor cells were found to be recruited locally and concurrently from periosteum and/or bone marrow/endosteum during bone repair. Periosteum and bone marrow/endosteum both gave rise to osteoblasts, whereas the periosteum was the major source of chondrocytes. Finally, results show that intrinsic and environmental signals modulate cell fate decisions within these tissues. In conclusion, this study sheds light into the origins of skeletal stem cells/progenitors during bone regeneration and indicates that periosteum, endosteum, and bone marrow contain pools of stem cells/progenitors with distinct osteogenic and chondrogenic potentials that vary with the tissue environment.

  14. Bone Metabolism on ISS Missions

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

    2014-01-01

    Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those

  15. Mechanisms influencing bone metabolism in chronic illness.

    PubMed

    Daci, E; van Cromphaut, S; Bouillon, R

    2002-01-01

    Bone is permanently renewed by the coordinated actions of bone-resorbing osteoclasts and bone-forming osteoblasts, which model and remodel bone structure during growth and adult life. The origin of osteoblastic cells (osteoblasts, osteocytes and bone-lining cells) differs from that of osteoclasts, but both cell groups communicate with each other using cytokines and cell-cell contact as to optimally maintain bone homeostasis. This communication in many ways uses the same players as the communication between cells in the immune system. During acute life-threatening illness massive bone resorption is the rule, while bone formation is suppressed. During chronic illness, the balance between bone formation and bone resorption also shifts, frequently resulting in decreased bone mass and density. Several factors may contribute to the osteopenia that accompanies chronic illness, the most important being undernutrition and low body weight, inflammatory cytokines, disorders of the neuroendocrine axis (growth hormone/IGF-1 disturbances, thyroid and gonadal deficiency), immobilization, and the long-term use of glucocorticoids. Their combined effects not only influence the generation and activity of all bone cells involved, but probably also regulate their life span by apoptotic mechanisms. Osteopenia or even osteoporosis and bone fragility, and before puberty also decreased linear growth and lower peak bone mass are therefore frequent consequences of chronic illnesses.

  16. Grapefruit juice modulates bone quality in rats.

    PubMed

    Deyhim, Farzad; Mandadi, Kranthi; Faraji, Bahram; Patil, Bhimanagouda S

    2008-03-01

    Hypogonadism and oxidative stress increase the risk for developing osteoporosis. The objective of this research was to evaluate the efficacy of drinking grapefruit juice on bone quality in orchidectomized (ORX) and non-ORX rats. Fifty-six 90-day-old male Sprague-Dawley rats were equally divided into four groups--non-ORX rats (sham), sham + grapefruit juice, ORX, and ORX + grapefruit juice--and treated for 60 days. Thereafter, all rats were sacrificed to determine the plasma antioxidant status, insulin-like growth factor I (IGF-I), and indices of bone turnover, bone quality, and calcium and magnesium concentrations in the bone, urine, and feces. Orchidectomy decreased (P < .05) antioxidant status, bone quality, and bone mineral contents and increased (P < .05) indices of bone turnover, urinary deoxypridinoline, calcium, and magnesium, and fecal calcium excretions. In contrast to the ORX group, ORX rats that drank grapefruit juice had an increase (P < .05) in antioxidant status, bone density, and bone mineral contents, delayed femoral fracture, and slowed down (P < .05) bone turnover rate and tended to have a decrease (P = .08) in urinary deoxypridinoline. In sham-treated animals, drinking grapefruit juice increased (P < .05) bone density and tended to increase the femoral strength. The concentration of IGF-I in the plasma was not affected across treatments. In conclusion, drinking grapefruit juice positively affected bone quality by enhancing bone mineral deposition in ORX rats and by improving bone density in non-ORX rats via an undefined mechanism.

  17. [Bone mineral density in renal osteodystrophy].

    PubMed

    Yamamoto, Noriaki

    2002-11-01

    Renal osteodystrophy can be classified into several disorders, which is now major problem in hemodialysis (HD) patients. Most of studies reported that the bone mineral density of HD patients decreased, but there exist the differences depending on many factors such as sex, bone site, years of HD, the type of disorders. The clinical usefulness of bone densitometry has been evaluated in many studies.

  18. Long-term response of femoral density to hip implant and bone fracture plate: Computational study using a mechano-biochemical model.

    PubMed

    Avval, Pouria Tavakkoli; Samiezadeh, Saeid; Bougherara, Habiba

    2016-02-01

    Although bone fracture plates can provide appropriate stability at the fracture site and lead to early patient mobilization, they significantly change the loading pattern in the bone after union (Stress shielding). This phenomenon results in a bone density decrease, which may cause premature failure of the implant. This paper presents the first study that quantifies the long-term response of femoral density to hip implantation and plating (lateral and anterior plating) using a mechano-biochemical model which considers the coupling effect between mechanical loading and biochemical affinities as stimuli for bone remodeling. The results showed that the regions directly beneath the plate experienced severe bone loss (i.e. up to ∼ -70%). However, some level of bone formation was observed in the vicinity of the most proximal and distal screw holes in both lateral and anterior plated femurs (i.e. up to ∼ +110%). The bone under the plate was divided into six zones. With respect to bone remodeling response, the findings revealed that anterior plating was not superior to lateral plating since the maximum and average bone losses among the zones in the anterior plated femur (i.e. -36% and -24%, respectively) were approximately the same as their corresponding values in the lateral plated femur (i.e. -38% and -24%, respectively). Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. [Retrospective study on CT findings on the sternal bone after bone marrow aspiration procedure in hematological patients].

    PubMed

    Fujita, Hiroshi; Nishimura, Shigeko; Oyama, Kazuyuki

    2009-12-01

    We retrospectively studied the CT findings of sternal bone in 129 patients with hematological diseases who underwent bone marrow aspiration in Tokyo Metropolitan Bokutoh Hospital between August 2005 and July 2007. Sternal findings demonstrated sternal foramen (3 cases), incomplete fracture (1 case) and irregularity and decreased bone density of the visceral cortical bone (first intercostal space: 66 cases, third intercostal space: 3 cases). Irregularity and decreased bone density of the visceral cortical bone were significantly related to findings of decreased bone density in the third lumbar spine, indicating osteoporosis. These findings suggest that sternal bones demonstrated various bone diseases such as sternal foramen, fracture and osteoporosis, and that bone marrow aspiration from sternal bones might not be as safe as previously thought.

  20. Animal Models of Bone Metastasis

    PubMed Central

    Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

    2015-01-01

    Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

  1. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  2. [Influences of resistance training on bone.

    PubMed

    Kawao, Naoyuki; Kaji, Hiroshi

    Resistance training has been known to be effective to maintain and improve bone mineral density(BMD)and bone strength. Resistance training in combination with other types of exercise might be effective for maintaining BMD in patients with osteoporosis. Resistance training improves a decrease in BMD through an enhancement of bone formation and a suppression of bone resorption. It is thought that resistance training might affect bone metabolism through direct biomechanical force on bone cells and endocrinological factors as well as the nervous system.

  3. Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance

    DTIC Science & Technology

    2008-05-01

    cell and the bone microenvironment (Siclari et al, 2006). Once the tumor cell has entered bone, the tumor cell secretes factors that act on bone... neomycin resistance gene expression. Decreasing AM promotes bone metastases by osteolytic breast cancer cells. Its role in breast cancer is different than...within bone that contribute to the incurability of the disease. Once breast cancer cells enter bone, a ‘vicious cycle’ develops between breast cancer

  4. Arsenic mobilizes Langerhans cell migration and induces Th1 response in epicutaneous protein sensitization via CCL21: a plausible cause of decreased Langerhans cells in arsenic-induced intraepithelial carcinoma.

    PubMed

    Lee, Chih-Hung; Hong, Chien-Hui; Yu, Chia-Li; Wang, Li-Fang; Clausen, Björn E; Liao, Wei-Ting; Huang, Shau-Ku; Chen, Gwo-Shing; Yu, Hsin-Su

    2012-05-01

    Arsenic, still a significant environmental threat in several regions in the world, induces various cancers, including lungs, skin, and bladder. Arsenic-induced Bowen's disease (As-BD) is generally an indolent cutaneous intraepithelial carcinoma in susceptible people. Patients with As-BD have been found to have attenuated contact hypersensitivity. Skin samples collected from these patients have reduced numbers of Langerhans cells (LCs), the major epidermal antigen presenting cells expressing Langerins. This study uses an epicutaneous protein sensitization model to investigate the mechanism through which LCs are decreased in As-BD. It further investigates the possibility that arsenic alters LC migration and polarizes Th responses. To do this, we patch-sensitized Balb/c mice or DT-treated Langerin-DTR mice (conditional depletion of Langerin(+) cells) with OVA or PBS, and fed them water containing 300 ppb arsenic or regular water for 200 μl for five days. Ninety-six hours after OVA sensitization, Langerin(+)EpCAM(+) cells in arsenic-treated WT mice were significantly increased in draining lymph nodes and decreased in epidermis without changes in the dermis. Lymph node cells from arsenic-treated WT mice were found to proliferate more than lymph node cells from control PBS-treated mice after OVA challenge in vitro. They also secreted more IFN-γ and IL-12, but not IL-4, IL-13, or IL-17. However, cell proliferation and the induction of IFN-γ by arsenic were found to be abolished in DT-treated Langerin-DTR mice. The expressions of CCL21 and CXCL12 were also increased in lymph nodes from arsenic-treated WT mice. The administration of a neutralizing antibody against CCL21, but not CXCL12, abolished the increase of LCs in lymph nodes in vivo. The results of this study, the first to study oral arsenic polarization of Th1 responses in epicutaneous protein sensitization through CCL21-mediated LC migration, suggest the chronicity of As-BD without invasion might result from

  5. Responds of Bone Cells to Microgravity: Ground-Based Research

    NASA Astrophysics Data System (ADS)

    Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

    2015-11-01

    Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

  6. Systemic therapy for bone metastases.

    PubMed

    Loftus, L S; Edwards-Bennett, S; Sokol, G H

    2012-04-01

    Accelerated bone loss in patients with cancer is a frequent problem that may result from invasion of the cancer to bone, paraneoplastic tumor proteins, and/or hormonal therapies utilized for cancer treatment. Patients with osteolytic bone disease from multiple myeloma and bone metastases from solid tumors may develop a vicious cycle of bone destruction involving both osteolytic and osteoblastic effects. Consequently, a variety of skeletal-related events (SREs) may occur, including pathological fractures, hypercalcemia, spinal cord compression, and the need for surgical intervention and radiation therapy. This article reviews the results of trials that investigated the safety and efficacy of pharmacologic agents, including bisphosphonates and denosumab, for treatment of bone metastases. This analysis is derived from an assessment of the medical literature. Beneficial systemic therapies for bone metastases have been developed to decrease SREs. Possible antitumor effects of the bisphosphonates are explored. In addition, the utility of markers of bone turnover in relation to response to therapy and survival, the safety and toxicity of bone-targeted therapies, treatment guidelines, and economic considerations are also discussed. Effective systemic therapies for metastatic bone disease are available. Ongoing and future research projects in this field are also presented.

  7. Multilayer porous UHMWPE scaffolds for bone defects replacement.

    PubMed

    Maksimkin, A V; Senatov, F S; Anisimova, N Yu; Kiselevskiy, M V; Zalepugin, D Yu; Chernyshova, I V; Tilkunova, N A; Kaloshkin, S D

    2017-04-01

    Reconstruction of the structural integrity of the damaged bone tissue is an urgent problem. UHMWPE may be potentially used for the manufacture of porous implants simulating as closely as possible the porous cancellous bone tissue. But the extremely high molecular weight of the polymer does not allow using traditional methods of foaming. Porous and multilayer UHMWPE scaffolds with nonporous bulk layer and porous layer that mimics cancellous bone architecture were obtained by solid-state mixing, thermopressing and washing in subcritical water. Structural and mechanical properties of the samples were studied. Porous UHMWPE samples were also studied in vitro and in vivo. The pores of UHMWPE scaffold are open and interconnected. Volume porosity of the obtained samples was 79±2%; the pore size range was 80-700μm. Strong connection of the two layers in multilayer UHMWPE scaffolds was observed with decreased number of fusion defects. Functionality of implants based on multilayer UHMWPE scaffolds is provided by the fixation of scaffolds in the bone defect through ingrowths of the connective tissue into the pores, which ensures the maintenance of the animals' mobility.

  8. Osteoinductive Effects of Glyceollins on Adult Mesenchymal Stromal/Stem Cells from Adipose Tissue and Bone Marrow

    USDA-ARS?s Scientific Manuscript database

    Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density (BMD) and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabol...

  9. Osteopontin deficiency increases bone fragility but preserves bone mass.

    PubMed

    Thurner, Philipp J; Chen, Carol G; Ionova-Martin, Sophi; Sun, Luling; Harman, Adam; Porter, Alexandra; Ager, Joel W; Ritchie, Robert O; Alliston, Tamara

    2010-06-01

    The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone quality, matrix material properties are biologically-defined and can be disrupted in skeletal disease. While mineral and collagen have been investigated in greater detail, the contribution of noncollagenous proteins such as osteopontin to bone matrix material properties remains unclear. Several roles have been ascribed to osteopontin in bone, many of which have the potential to impact material properties. To elucidate the role of osteopontin in bone quality, we evaluated the structure, composition, and material properties of bone from osteopontin-deficient mice and wild-type littermates at several length scales. Most importantly, the results show that osteopontin deficiency causes a 30% decrease in fracture toughness, suggesting an important role for OPN in preventing crack propagation. This significant decline in fracture toughness is independent of changes in whole bone mass, structure, or matrix porosity. Using nanoindentation and quantitative backscattered electron imaging to evaluate osteopontin-deficient bone matrix at the micrometer level, we observed a significant reduction in elastic modulus and increased variability in calcium concentration. Matrix heterogeneity was also apparent at the ultrastructural level. In conclusion, we find that osteopontin is essential for the fracture toughness of bone, and reduced toughness in osteopontin-deficient bone may be related to the increased matrix heterogeneity observed at the micro-scale. By exploring the effects of osteopontin deficiency on bone matrix material properties, composition and organization, this study suggests that reduced fracture toughness is one mechanism by which loss of noncollagenous proteins contribute

  10. Osteopontin Deficiency Increases Bone Fragility but Preserves Bone Mass

    PubMed Central

    Thurner, Philipp J.; Chen, Carol G.; Ionova-Martin, Sophi; Sun, Luling; Harman, Adam; Porter, Alexandra; Ager, Joel W.; Ritchie, Robert O.; Alliston, Tamara

    2010-01-01

    The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone quality, matrix material properties are biologically-defined and can be disrupted in skeletal disease. While mineral and collagen have been investigated in greater detail, the contribution of noncollagenous proteins such as osteopontin to bone matrix material properties remains unclear. Several roles have been ascribed to osteopontin in bone, many of which have the potential to impact material properties. To elucidate the role of osteopontin in bone quality, we evaluated the structure, composition, and material properties of bone from osteopontin-deficient mice and wild-type littermates at several length scales. Most importantly, the results show that osteopontin deficiency causes a 30% decrease in fracture toughness, suggesting an important role for OPN in preventing crack propagation. This significant decline in fracture toughness is independent of changes in whole bone mass, structure, or matrix porosity. Using nanoindentation and quantitative backscattered electron imaging to evaluate osteopontin-deficient bone matrix at the micrometer level, we observed a significant reduction in elastic modulus and increased variability in calcium concentration. Matrix heterogeneity was also apparent at the ultrastructural level. In conclusion, we find that osteopontin is essential for the fracture toughness of bone, and reduced toughness in osteopontin-deficient bone may be related to the increased matrix heterogeneity observed at the micro-scale. By exploring the effects of osteopontin-deficiency on bone matrix material properties, composition and organization, this study suggests that reduced fracture toughness is one mechanism by which loss of noncollagenous proteins contribute

  11. Drinking water fluoridation and bone.

    PubMed

    Allolio, B; Lehmann, R

    1999-01-01

    Drinking water fluoridation has an established role in the prevention of dental caries, but may also positively or negatively affect bone. In bone fluoride is incorporated into hydroxylapatite to form the less soluble fluoroapatite. In higher concentrations fluoride stimulates osteoblast activity leading to an increase in cancellous bone mass. As optimal drinking water fluoridation (1 mg/l) is widely used, it is of great interest, whether long-term exposition to artificial water fluoridation has any impact on bone strength, bone mass, and -- most importantly -- fracture rate. Animal studies suggest a biphasic pattern of the effect of drinking water fluoridation on bone strength with a peak strength at a bone fluoride content of 1200 ppm followed by a decline at higher concentrations eventually leading to impaired bone quality. These changes are not paralleled by changes in bone mass suggesting that fluoride concentrations remain below the threshold level required for activation of osteoblast activity. Accordingly, in most epidemiological studies in humans bone mass was not altered by optimal drinking water fluoridation. In contrast, studies on the effect on hip fracture rate gave conflicting results ranging from an increased fracture incidence to no effect, and to a decreased fracture rate. As only ecological studies have been performed, they may be biased by unknown confounding factors -- the so-called ecological fallacy. However, the combined results of these studies indicate that any increase or decrease in fracture rate is likely to be small. It has been calculated that appropriately designed cohort studies to solve the problem require a sample size of >400,000 subjects. Such studies will not be performed in the foreseeable future. Future investigations in humans should, therefore, concentrate on the effect of long-term drinking water fluoridation on bone fluoride content and bone strength.

  12. Evidence for arrested bone formation during spaceflight

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Bobyn, J. D.; Duvall, P.; Morey, E. R.; Baylink, D. J.; Spector, M.

    1982-01-01

    Addressing the question of whether the bone formed in space is unusual, the morphology of bone made at the tibial diaphysis of rats before, during, and after spaceflight is studied. Evidence of arrest lines in the bone formed in space is reported suggesting that bone formation ceases along portions of the periosteum during spaceflight. Visualized by microradiography, the arrest lines are shown to be less mineralized than the surrounding bone matrix. When viewed by scanning electron microscopy, it is seen that bone fractures more readily at the site of an arrest line. These observations are seen as suggesting that arrest lines are a zone of weakness and that their formation may result in decreased bone strength in spite of normalization of bone formation after flight. The occurrence, location, and morphology of arrest lines are seen as suggesting that they are a visible result of the phenomenon of arrested bone formation.

  13. Talking Bones.

    ERIC Educational Resources Information Center

    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)

  14. Talking Bones.

    ERIC Educational Resources Information Center

    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. Microgravity and bone cell mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R. G.; Veldhuijzen, J. P.; Van Loon, J. J. W. A.

    2003-10-01

    mechanosensitivity of bone cells is altered under near weightlessness conditions, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts. In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

  16. The response of bone to unloading

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  17. The response of bone to unloading

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  18. Percutaneous cementoplasty for the treatment of extraspinal painful bone lesion, a prospective study.

    PubMed

    Iannessi, A; Amoretti, N; Marcy, P-Y; Sedat, J

    2012-11-01

    The current gold standard treatment of localized painful bone lesion is radiotherapy but this technique has limitations. Our study aims to demonstrate that cementoplasty is an efficient alternative for these palliatives indications when lesions involve extraspinal bones. We prospectively followed 20 patients who received a percutaneous cementoplasty on painful lytic bone lesions between May 2008 and May 2010. Seventeen patients also had difficulty walking in relation to the pain experienced. The clinical indication for treatment was severe pain (≥4 on the numeric scale) due to bone lesion on CT or MRI. All procedures (except one) were performed under local anesthesia. Feasibility was 100% without immediate complications. The patients experienced a significant and rapid decrease of their pain (4.1 points, P<000.1) and this effect was sustained over the long term (7.75 months of follow-up on average). Sixty-four percent of patients treated on the lower limbs and pelvis improved mobility. In our experience, percutaneous cementoplasty may be a safe and effective palliative treatment for localized painful lytic lesion. Combining CT and fluoroscopic guidance seems to be the safer option because of extravertebral localization. Smart fill of the bone and careful selection of patient determine the effectiveness of the procedure. Diffuse painful lesions and long bone diaphysis should not be good indications. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  19. Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization

    PubMed Central

    Jiang, Shuxian; Alberich-Jorda, Meritxell; Zagozdzon, Radoslaw; Parmar, Kalindi; Fu, Yigong; Mauch, Peter; Banu, Naheed; Makriyannis, Alexandros; Tenen, Daniel G.; Avraham, Shalom; Groopman, Jerome E.

    2011-01-01

    Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB1 and CB2) and the enzymes involved in their biosynthesis and degradation. However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB2 receptors are expressed in human and murine HSPCs. On ligand stimulation with CB2 agonists, CB2 receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and Gαi-Rac1 pathways. In vivo, the CB2 agonist AM1241 induced mobilization of murine HSPCs with short- and long-term repopulating abilities. In addition, granulocyte colony-stimulating factor -induced mobilization of HSPCs was significantly decreased by specific CB2 antagonists and was impaired in Cnr2−/− cannabinoid type 2 receptor knockout mice. Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB2/CB2 agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs. Thus, CB2 agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation. PMID:21063029

  20. Augmentation of peri-implant bone improves implant stability: quantification using simulated bone loss.

    PubMed

    Wirth, Andreas J; Müller, Ralph; van Lenthe, G Harry

    2012-02-01

    Low bone quality, such as induced by osteoporosis, is considered a main factor leading to failure of fracture fixations. Peri-implant bone augmentation has been proposed as a means of reducing failure rates in osteoporotic bone by improving implant stability. The beneficial effects of pharmacological augmentation of bone in the immediate vicinity of the implant have been demonstrated. Yet, a quantitative understanding of the role of peri-implant bone in implant stability is lacking. Therefore, the aim of our study was to quantify the effects of bone loss and peri-implant bone augmentation on implant stability using image-based finite element analyses. Using a validated model, we simulated how osteoporotic bone loss would affect implant stability in human humeral heads. We also quantified how augmentation of peri-implant bone can enhance implant stability. Our simulations revealed that a 30% reduction in bone mass led to a 50% decrease in implant stability. We also found that peri-implant bone augmentation increased implant stability and that the efficiency of bone augmentation decreased with increasing peri-implant distance. These findings highlight the strong effect that bone loss has on implant fixation and the potential of peri-implant bone augmentation for improving implant anchorage in low quality bone. Copyright © 2011 Orthopaedic Research Society.

  1. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    NASA Technical Reports Server (NTRS)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  2. Paget's Disease of Bone

    MedlinePlus

    ... page please turn Javascript on. Paget's Disease of Bone What is Paget's Disease of Bone? Click for more information Enlarged and Misshapen Bones Paget's disease of bone causes affected bones to ...

  3. Effect of space flight on sodium, copper, manganese and magnesium content in the skeletal bones

    NASA Technical Reports Server (NTRS)

    Prokhonchukov, A. A.; Taitsev, V. P.; Shakhunov, B. A.; Zhizhina, V. A.; Kolesnik, A. G.; Komissarova, N. A.

    1979-01-01

    Sodium content decreased in the human skeletal bones and rose in the rat bones following space flight. In man copper content rose in the femoral bone and decreased in the vertebral body and the sternum, but was unchanged in the rest of the bones. Magnesium content was decreased in the femoral bone and the sternum, and in the vertebrae, but remained unchanged in the rest of the bones. Possible mechanisms of the changes detected are discussed.

  4. Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

    NASA Astrophysics Data System (ADS)

    Kasai, Takao; Matsumura, Sachiko; Iizuka, Tadashi; Shiba, Kiyotaka; Kanamori, Takeshi; Yudasaka, Masako; Iijima, Sumio; Yokoyama, Atsuro

    2011-02-01

    A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possible medical uses such as in drug delivery systems. It was reported that some kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. However, the effect of CNHs on bone tissue has not been clarified. The purpose of this study was to evaluate the effect of CNHs on bone regeneration and their possible application for guided bone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porous polytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created in rats and covered by a membrane with/without CNHs. At two weeks, bone formation under the membrane with CNHs had progressed more than under that without CNHs and numerous macrophages were observed attached to CNHs. At eight weeks, there was no significant difference in the amount of newly formed bone between the groups and the appearance of macrophages was decreased compared with that at two weeks. Newly formed bone attached to some CNHs directly. These results suggest that macrophages induced by CNHs are related to bone regeneration. In conclusion, the present study indicates that CNHs are compatible with bone tissue and effective as a material for GBR.