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Sample records for affects bone homeostasis

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  3. [Regulation of bone homeostasis by glucose].

    Science.gov (United States)

    Fukasawa, Kazuya; Hinoi, Eiichi

    2016-08-01

    Synthesis of type Ⅰ collagen, a major component of the bone matrix, precedes the expression of Runt-related transcription factor 2(Runx2), a master regulator in osteoblast differentiation. Thus, a direct link between osteoblast differentiation and bone formation is seemingly absent, and how these are maintained in a coordinated matter remains unclear. It was recently demonstrated that osteoblasts depend on glucose, which glucose transporter type 1(GLUT1)takes up as an energy source, and it was found that glucose uptake promotes osteoblast differentiation and bone formation via AMP-activated protein kinase. It was also shown that Runx2 upregulates GLUT1 expression, and this Runx2-GLUT1 feedforward regulation integrates and coordinates osteoblast differentiation and bone formation throughout life. These previous findings revealed that the energy metabolism balance in osteoblasts integrates the differentiation and function of osteoblasts, and re-emphasized the importance of crosstalk between bone and sugar metabolism. PMID:27461500

  4. Does methamphetamine affect bone metabolism?

    International Nuclear Information System (INIS)

    There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10 mg/kg METH groups (n = 6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5 mg/kg METH showed an increased locomotor activity, whereas those receiving 10 mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5 mg/kg METH group, but not in the 10 mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5 mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10 mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that

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

    Directory of Open Access Journals (Sweden)

    Edgardo Rodríguez-Carballo

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

  6. Agent-Based Deterministic Modeling of the Bone Marrow Homeostasis.

    Science.gov (United States)

    Kurhekar, Manish; Deshpande, Umesh

    2016-01-01

    Modeling of stem cells not only describes but also predicts how a stem cell's environment can control its fate. The first stem cell populations discovered were hematopoietic stem cells (HSCs). In this paper, we present a deterministic model of bone marrow (that hosts HSCs) that is consistent with several of the qualitative biological observations. This model incorporates stem cell death (apoptosis) after a certain number of cell divisions and also demonstrates that a single HSC can potentially populate the entire bone marrow. It also demonstrates that there is a production of sufficient number of differentiated cells (RBCs, WBCs, etc.). We prove that our model of bone marrow is biologically consistent and it overcomes the biological feasibility limitations of previously reported models. The major contribution of our model is the flexibility it allows in choosing model parameters which permits several different simulations to be carried out in silico without affecting the homeostatic properties of the model. We have also performed agent-based simulation of the model of bone marrow system proposed in this paper. We have also included parameter details and the results obtained from the simulation. The program of the agent-based simulation of the proposed model is made available on a publicly accessible website. PMID:27340402

  7. ["Osteo-neural" related factors - bridge over bone homeostasis].

    Science.gov (United States)

    Sato, Tsuyoshi

    2016-08-01

    Bone tissues including bone marrow are comprised of various cells. A growing body of evidence suggests that nerve cells which exist in and around bone such as periosteal and bone marrow build a close relationship with bone cells. Namely, it was revealed that central nervous system governs bone tissues via peripheral nervous system and neurotransmitters or cytokines play a role for the communication between bone and nerve in the last decade. In this paper, I would like to review "osteo-neural" related factors which has been well-documented so far. PMID:27461495

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

    Institute of Scientific and Technical Information of China (English)

    Mengrui Wu; Guiqian Chen; and Yi-Ping Li

    2016-01-01

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

  9. Regulation of osteoclast homeostasis and inflammatory bone loss by MFG-E81

    OpenAIRE

    Abe, T.; Shin, J.; Hosur, K.; Udey, M C; Chavakis, T.; Hajishengallis, G

    2014-01-01

    The glycoprotein milk fat globule-EGF factor 8 (MFG-E8) is expressed in several tissues and mediates diverse homeostatic functions. However, whether MFG-E8 plays a role in bone homeostasis has not been established. Here we show for the first time that osteoclasts express and are regulated by MFG-E8. Bone marrow-derived osteoclast precursors (OCPs) from MFG-E8–deficient (Mfge8−/−) mice underwent increased RANKL-induced osteoclastogenesis leading to enhanced resorption pit formation as compared...

  10. Coupling Hydroxyapatite Nanocrystals with Lactoferrin as a Promising Strategy to Fine Regulate Bone Homeostasis.

    Directory of Open Access Journals (Sweden)

    Monica Montesi

    Full Text Available Lactoferrin (LF is an interesting glycoprotein in the field of bone biology for its regulatory effect on cells involved in bone remodeling, that results compromised in several pathological conditions, as osteoporosis. In a previous study we observed that the coupling of LF and biomimetic hydroxyapatite nanocrystals (HA, a material well-known for its bioactivity and osteoconductive properties, leads to a combined effect in the induction of osteogenic differentiation of mesenchymal stem cells. On the basis of this evidence, the present study is an extension of our previous work aiming to investigate the synergistic effect of the coupling of HA and LF on bone homeostasis. Biomimetic HA nanocrystals were synthesized and functionalized with LF (HA-LF and then pre-osteoblasts (MC3T3-E1 and monocyte/macrophage cells lines (RAW 264.7, using as osteoclastogenesis in vitro model, were cultured separately or in co-culture in presence of HA-LF. The results clearly revealed that HA and LF act in synergism in the regulation of the bone homeostasis, working as anabolic factor for osteoblasts differentiation and bone matrix deposition, and as inhibitor of the osteoclast formation and activity.

  11. Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis.

    Science.gov (United States)

    Sharma, Monika; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Prasad, Rajendra

    2012-01-01

    This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol. However, CUR alone at its synergistic concentration (lower than MIC50), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in phosphoglycerides (PGLs) composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR. Our study first time shows that CUR, for its antifungal activity, targets and down regulates delta 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of reactive oxygen species (ROS) and cell death. PMID:22201946

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

    Science.gov (United States)

    Williams, Bart O

    2016-03-01

    Alterations in components of the Wnt signaling pathway are associated with altered bone development and homeostasis in several human diseases. We created genetically engineered mouse models (GEMMs) that mimic the cellular defect associated with the Porcupine mutations in patients with Goltz Syndrome/Focal Dermal Hypoplasia. These GEMMs were established by utilizing mice containing a conditionally inactivatable allele of Wntless/GPR177 (a gene encoding a protein required for the transport of Porcupine-modified ligand to the plasma membrane for secretion). We crossed this strain to another which drives cre-mediated gene deletion in mature osteoblasts (Osteocalcin-cre) resulted in mice lacking the ability to secrete Wnt ligands in this cell type. These mice displayed severely reduced bone mass and provide a model to understand the effects of disrupting the ability to secrete Wnt ligands on the skeletal system. © 2016 Wiley Periodicals, Inc. PMID:26818176

  13. The dual origins of affect in nightmares: the roles of physiological homeostasis and memory.

    Science.gov (United States)

    Schulze, Georg

    2006-01-01

    Strong negative affect is a key and distressing ingredient of nightmares. Affect in nightmares arises either from the new generation of affective states due to physiological imbalances that occur during sleep or from the reactivation of affect-laden memories. The disruption of physiological balance produces a negative hedonic state, restoration of this balance produces a positive hedonic state, and when balance is attained, a neutral hedonic state results. As a result, hedonic states provoke behaviors in defense of homeostasis, then guide and terminate them. When, due to inadvertent behavior, a pronounced disruption of homeostasis occurs after sleep onset, the resultant strong negative hedonic state is likely to precipitate a nightmare and may lead to awakening. During normal wakefulness, associations of the interplay between stimuli and behaviors that disrupt homeostasis, those that restore homeostasis, and the affective states generated in the process, are committed to memory as affecto-cognitive ensembles. Sleep serves to build or rebuild neural architecture to effect development or to compensate for use- or disease-related wear (e.g. repair oxidative damage). Dreaming serves to synchronize or resynchronize such modified neural circuits with each other and those not modified. Hence, during dreaming, affecto-cognitive ensembles may get reactivated as part of the synchronization process. Where such an ensemble contains strong negative affect (i.e., due to strong affect generated during the original experience), a nightmare may be precipitated. Although both can occur throughout life, the latter type of nightmare is more likely in adults and the former in young children. For the latter memory-based behavioral therapy and for the former education and care are expected to be useful. For both types of nightmare, because strong negative affect is deemed dependent on noradrenergic outflow from the locus coeruleus, the administration of alpha-adrenergic antagonists will

  14. Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis.

    Science.gov (United States)

    Herbert, B A; Novince, C M; Kirkwood, K L

    2016-06-01

    Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and preclinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast-mediated bone remodeling, which subsequently leads to net alveolar bone loss. PMID:26197893

  15. Tooth dentin defects reflect genetic disorders affecting bone mineralization

    OpenAIRE

    Vital, S. Opsahl; Gaucher, C.; Bardet, C; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

    2012-01-01

    Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding ...

  16. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis.

    Science.gov (United States)

    Thaler, Roman; Sturmlechner, Ines; Spitzer, Silvia; Riester, Scott M; Rumpler, Monika; Zwerina, Jochen; Klaushofer, Klaus; van Wijnen, Andre J; Varga, Franz

    2015-04-01

    Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria. Recombinant Saa3 protein functionally inhibits osteoblast differentiation as reflected by reductions in the expression of osteoblast markers and decreased mineralization in newborn mouse calvaria. Yet, Saa3 protein enhances osteoclastogenesis in mouse macrophages/monocytes based on the number of multinucleated and tartrate-resistant alkaline phosphatase-positive cells and Calcr mRNA expression. Depletion of Saa3 in MLO osteocytes results in the loss of the mature osteocyte phenotype. Recombinant osteocalcin, which is reciprocally regulated with Saa3 at the osteoblast/osteocyte transition, attenuates Saa3 expression in MLO-Y4 osteocytes. Mechanistically, Saa3 produced by MLO-Y4 osteocytes is integrated into the extracellular matrix of MC3T3-E1 osteoblasts, where it associates with the P2 purinergic receptor P2rx7 to stimulate Mmp13 expression via the P2rx7/MAPK/ERK/activator protein 1 axis. Our data suggest that Saa3 may function as an important coupling factor in bone development and homeostasis. PMID:25491310

  17. In vitro study of the osteocytes response to hypoxia and their regulation of bone homeostasis

    OpenAIRE

    Montesi, Monica

    2014-01-01

    Bone remodelling is a fundamental mechanism for removing and replacing bone during adaptation of the skeleton to mechanical loads. Skeletal unloading leads to severe hypoxia (1%O2) in the bone microenvironment resulting in imbalanced bone remodelling that favours bone resorption. Hypoxia, in vivo, is a physiological condition for osteocytes, 5% O2 is more likely physiological for osteocytes than 20% O2, as osteocytes are embedded deep inside the mineralized bone matrix. Osteocytes are thought...

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

    OpenAIRE

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

    2015-01-01

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

  19. Tyroserleutide tripeptide affects calcium homeostasis of human hepatocarcinoma BEL-7402 cells

    Institute of Scientific and Technical Information of China (English)

    FU Zheng; LU Rong; LI Guoli; ZHAO Lan; GAO Weizhen; CHE Xuchun; JIAN Xu; ZHOU Chunlei; YAO Zhi

    2005-01-01

    This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg·kg-1·d-1, 160μg·kg-1·d-1 and 320μg·kg-1·d-1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium overload. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p<0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.

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

    Science.gov (United States)

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

    2003-10-01

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

  1. Deposition of plutonium-238 injected intratracheally within different skeleton bones iron homeostasis being changed

    International Nuclear Information System (INIS)

    A study was made of the distribution of plutonium-239 injected intratracheally within different bones of the skeleton, the iron status in the blood being changed. The iron preparation caused 2.5-3-fold decrease in the plutonium loading onto cancellous bone tissue that displayed, in ordinary conditions, a higher tropism to the radionuclide than a cortical highly mineralized bone did

  2. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    Science.gov (United States)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  3. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

    Science.gov (United States)

    Zerwekh, J. E.; Ruml, L. A.; Gottschalk, F.; Pak, C. Y.; Blomqvist, C. G. (Principal Investigator)

    1998-01-01

    This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal

  4. Loss of sugar detection by GLUT2 affects glucose homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Emilie Stolarczyk

    Full Text Available BACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets.

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

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    Neslihan Başcıl Tütüncü

    2008-05-01

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

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

    Science.gov (United States)

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

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

  7. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Candelario, Jose; Borrego, Stacey [Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Reddy, Sita, E-mail: sitaredd@usc.edu [Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Comai, Lucio, E-mail: comai@usc.edu [Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)

    2011-02-01

    levels of the basal transcription factor TATA-binding protein (TBP) and global transcription, and severely limited cell growth. Expression of a prelamin A variant that cannot be farnesylated, although did not appreciably influence cell growth, resulted in the formation of lamin A nucleoplasmic foci and caused, in a minor subpopulation of cells, changes in nuclear morphology that were accompanied by reduced levels of TBP and transcription. In contrast, expression of mature lamin A did not affect any of these parameters. These data demonstrate that accumulation of any partially processed prelamin A protein alters cellular homeostasis to some degree, even though the most dramatic effects are caused by variants with a permanently farnesylated carboxyl-terminal tail.

  8. ARTD1 regulates osteoclastogenesis and bone homeostasis by dampening NF-κB-dependent transcription of IL-1β.

    Science.gov (United States)

    Robaszkiewicz, Agnieszka; Qu, Chao; Wisnik, Ewelina; Ploszaj, Tomasz; Mirsaidi, Ali; Kunze, Friedrich A; Richards, Peter J; Cinelli, Paolo; Mbalaviele, Gabriel; Hottiger, Michael O

    2016-01-01

    While ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) and its enzymatic activity have been shown to be important for reprogramming and differentiation of cells, such as during adipogenesis, their role and mechanism in regulating osteoclastogenesis and bone homeostasis are largely unknown. Here, in cell culture-based RANKL-induced osteoclastogenesis models, we show that silencing of ARTD1 or inhibition of its enzymatic activity enhances osteoclast differentiation and function. As a consequence of ARTD1 silencing or inhibition, the recruitment of p65/RelA to the IL-1β promoter, which is associated with transcriptionally active histone marks, IL-1β expression and inflammasome-dependent secretion of IL-1β are enhanced. This subsequently promotes sustained induction of the transcription factor Nfatc1/A and osteoclastogenesis in an autocrine manner via the IL-1 receptor. In vivo, Artd1-deficient mice display significantly decreased bone mass as a consequence of increased osteoclast differentiation. Accordingly, the expression of osteoclast markers is enhanced in mutant compared to wild-type mice. Together, these results indicate that ARTD1 controls osteoclast development and bone remodelling via its enzymatic activity by modulating the epigenetic marks surrounding the IL-1β promoter and expression of IL-1β and subsequently also Nfatc1/A. PMID:26883084

  9. Estrogen receptor-α expression in neuronal cells affects bone mass

    OpenAIRE

    Ohlsson, Claes; Engdahl, Cecilia; Börjesson, Anna E; Sara H Windahl; Studer, Erik; Westberg, Lars; Eriksson, Elias; Koskela, Antti; Tuukkanen, Juha; Krust, Andree; Chambon, Pierre; Carlsten, Hans; Lagerquist, Marie K

    2012-01-01

    It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-α (ERα) expression for bone mass. Nestin-Cre mice were crossed with ERαflox mice to genera...

  10. Mineral and Skeletal Homeostasis Influence the Manner of Bone Loss in Metabolic Osteoporosis due to Calcium-Deprived Diet in Different Sites of Rat Vertebra and Femur

    Directory of Open Access Journals (Sweden)

    Marzia Ferretti

    2015-01-01

    Full Text Available Rats fed calcium-deprived diet develop osteoporosis due to enhanced bone resorption, secondary to parathyroid overactivity resulting from nutritional hypocalcemia. Therefore, rats provide a good experimental animal model for studying bone modelling alterations during biochemical osteoporosis. Three-month-old Sprague-Dawley male rats were divided into 4 groups: (1 baseline, (2 normal diet for 4 weeks, (3 calcium-deprived diet for 4 weeks, and (4 calcium-deprived diet for 4 weeks and concomitant administration of PTH (1-34 40 µg/Kg/day. Histomorphometrical analyses were made on cortical and trabecular bone of lumbar vertebral body as well as of mid-diaphysis and distal metaphysis of femur. In all rats fed calcium-deprived diet, despite the reduction of trabecular number (due to the maintenance of mineral homeostasis, an intense activity of bone deposition occurs on the surface of the few remaining trabeculae (in answering to mechanical stresses and, consequently, to maintain the skeletal homeostasis. Different responses were detected in different sites of cortical bone, depending on their main function in answering mineral or skeletal homeostasis. This study represents the starting point for work-in-progress researches, with the aim of defining in detail timing and manners of evolution and recovery of biochemical osteoporosis.

  11. [Great Scandinavian Jahre Prize 1993. Studies of cartilage and bone yields new knowledge of tissue homeostasis].

    Science.gov (United States)

    Heinegård, D

    1994-01-01

    Increased knowledge of connective tissue, such as cartilage and bone, has improved our understanding of tissue replenishment under normal and pathological conditions. Although developments in this field are still at an early stage, it is already possible to discern avenues for future development leading to new diagnostic and therapeutic methods in connective tissue diseases. In this article, Dick Heinegård, the second recipient of the Jahre Prize for 1993, gives an account of his research. PMID:8121785

  12. One carbon metabolism and bone homeostasis and remodeling: A review of experimental research and population studies.

    Science.gov (United States)

    Feigerlova, Eva; Demarquet, Lea; Guéant, Jean-Louis

    2016-07-01

    Homocysteine (HCY) is a degradation product of the methionine pathway. The B vitamins, in particular vitamin B12 and folate, are the primary nutritional determinant of HCY levels and therefore their deficiencies result in hyperhomocysteinaemia (HHCY). Prevalence of hyperhomocysteinemia (HHCY) and related dietary deficiencies in B vitamins and folate increase with age and have been related to osteoporosis and abnormal development of epiphyseal cartilage and bone in rodents. Here we provide a review of experimental and population studies. The negative effects of HHCY and/or B vitamins and folate deficiencies on bone formation and remodeling are documented by cell models, including primary osteoblasts, osteoclast and bone progenitor cells as well as by animal and human studies. However, underlying pathophysiological mechanisms are complex and remain poorly understood. Whether these associations are the direct consequences of impaired one carbon metabolism is not clarified and more studies are still needed to translate these findings to human population. To date, the evidence is limited and somewhat conflicting, however further trials in groups most vulnerable to impaired one carbon metabolism are required. PMID:27086080

  13. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    OpenAIRE

    Yan, Shengmin; Zhang, Hongxia; ZHENG, FEI; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-01-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is stil...

  14. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome

    OpenAIRE

    Ravera, Silvia; Dufour, Carlo; Cesaro, Simone; Bottega, Roberta; Faleschini, Michela; Cuccarolo, Paola; Corsolini, Fabio; Usai, Cesare; Columbaro, Marta; Cipolli, Marco; Savoia, Anna; Degan, Paolo; Cappelli, Enrico

    2016-01-01

    Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demo...

  15. Exposure to atrazine affects the expression of key genes in metabolic pathways integral to energy homeostasis in Xenopus laevis tadpoles

    Energy Technology Data Exchange (ETDEWEB)

    Zaya, Renee M., E-mail: renee.zaya@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Amini, Zakariya, E-mail: zakariya.amini@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Whitaker, Ashley S., E-mail: ashley.s.whitaker@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States); Ide, Charles F., E-mail: charles.ide@wmich.edu [Great Lakes Environmental and Molecular Sciences Center, Department of Biological Sciences, 3425 Wood Hall, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo, MI 49008 (United States)

    2011-08-15

    In our laboratory, Xenopus laevis tadpoles exposed throughout development to 200 or 400 {mu}g/L atrazine, concentrations reported to periodically occur in puddles, vernal ponds and runoff soon after application, were smaller and had smaller fat bodies (the tadpole's lipid storage organ) than controls. It was hypothesized that these changes were due to atrazine-related perturbations of energy homeostasis. To investigate this hypothesis, selected metabolic responses to exposure at the transcriptional and biochemical levels in atrazine-exposed tadpoles were measured. DNA microarray technology was used to determine which metabolic pathways were affected after developmental exposure to 400 {mu}g/L atrazine. From these data, genes representative of the affected pathways were selected for assay using quantitative real time polymerase chain reaction (qRT-PCR) to measure changes in expression during a 2-week exposure to 400 {mu}g/L. Finally, ATP levels were measured from tadpoles both early in and at termination of exposure to 200 and 400 {mu}g/L. Microarray analysis revealed significant differential gene expression in metabolic pathways involved with energy homeostasis. Pathways with increased transcription were associated with the conversion of lipids and proteins into energy. Pathways with decreased transcription were associated with carbohydrate metabolism, fat storage, and protein synthesis. Using qRT-PCR, changes in gene expression indicative of an early stress response to atrazine were noted. Exposed tadpoles had significant decreases in acyl-CoA dehydrogenase (AD) and glucocorticoid receptor protein (GR) mRNA after 24 h of exposure, and near-significant (p = 0.07) increases in peroxisome proliferator-activated receptor {beta} (PPAR-{beta}) mRNA by 72 h. Decreases in AD suggested decreases in fatty acid {beta}-oxidation while decreases in GR may have been a receptor desensitization response to a glucocorticoid surge. Involvement of PPAR-{beta}, an energy

  16. Plant natriuretic peptides: Systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts

    KAUST Repository

    Gehring, Christoph A

    2010-09-01

    Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3′,5′-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apo-ptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs. Copyright © 2013 by The American Federation for Medical Research.

  17. Factors Affecting Bone Mineral Density in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Azin Ayatollahi

    2013-01-01

    Full Text Available Background: Multiple sclerosis (MS is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD.Methods: 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA. The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS. The patient’s quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29.Results: Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001, but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL, disease duration and BMD of both site.Conclusion: As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients

  18. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    Science.gov (United States)

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  19. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.

    Science.gov (United States)

    Ravera, Silvia; Dufour, Carlo; Cesaro, Simone; Bottega, Roberta; Faleschini, Michela; Cuccarolo, Paola; Corsolini, Fabio; Usai, Cesare; Columbaro, Marta; Cipolli, Marco; Savoia, Anna; Degan, Paolo; Cappelli, Enrico

    2016-01-01

    Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca(2+)]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials. PMID:27146429

  20. Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism

    OpenAIRE

    Welty, Nathan E.; Staley, Christopher; Ghilardi, Nico; Sadowsky, Michael J.; Igyártó, Botond Z.; Kaplan, Daniel H.

    2013-01-01

    Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103+ subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103+CD11b+ LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC–T cell interactions were not required for Th17 development, as this response was inta...

  1. Exercise training of late-pregnant and nonpregnant dairy cows affects physical fitness and acid-base homeostasis.

    Science.gov (United States)

    Davidson, J A; Beede, D K

    2009-02-01

    The objective was to determine if exercise training improves physical fitness of nonlactating, late-pregnant and nonpregnant multiparous Holstein cows and alters acid-base homeostasis during an exercise test on a treadmill. Twenty-six pairs (each pair having 1 late-pregnant and 1 nonpregnant) of cows were assigned to treatments of exercise training or no exercise. Exercise training was walking (1.25 to 1.5 h at 3.25 km/h) every other day in an outdoor mechanical walker for 70 d. Cows completed treadmill exercise tests on d 0, 30, and 60 of the experiment or about d 70, 40, and 10 before expected parturition of the pregnant cow of each pair. On d 0, physical fitness was similar among all cows based on durations of treadmill tests, heart rates, and acid-base measurements at given workloads (21.1 +/- 0.6 min; 144 +/- 2.2 beats per min; plasma lactate 3.1 +/- 1.9 mmol/L; and venous blood pH 7.44 +/- 0.0035, respectively). After 60 d of training, exercised cows walked longer during treadmill exercise tests compared with nonexercised cows (23.7 vs. 18.3 +/- 0.85 min, respectively), indicating greater physical fitness (pooled across pregnancy status). Heart rates and plasma lactate concentrations at given workloads were less (144 vs. 156 +/- 2.7 beats per min; and 1.4 vs. 3.2 +/- 0.24 mmol/L for exercised compared with nonexercised cows, respectively). Additionally, exercised cows more effectively maintained acid-base homeostasis during treadmill tests compared with nonexercised cows. Metabolic, endocrine, and nutritional demands associated with late pregnancy did not affect responses differently to exercise training for late-pregnant compared with nonpregnant cows. Overall, exercise training of late-pregnant and nonpregnant cows for 60 d improved physical fitness. PMID:19164665

  2. Neutrophil Homeostasis and Periodontal Health in Children and Adults

    OpenAIRE

    Hajishengallis, E.; Hajishengallis, G

    2014-01-01

    This review summarizes the current state of knowledge on neutrophil basic biology and discusses how the breakdown of neutrophil homeostasis affects periodontal health. The homeostasis of neutrophils is tightly regulated through coordinated bone marrow production, release into the circulation, transmigration to and activation in peripheral tissues, and clearance of senescent neutrophils. Dysregulation of any of these homeostatic mechanisms at any age can cause severe periodontitis in humans an...

  3. Knockdown of the coenzyme Q synthesis gene Smed-dlp1 affects planarian regeneration and tissue homeostasis.

    Science.gov (United States)

    Shiobara, Yumiko; Harada, Chiaki; Shiota, Takeshi; Sakamoto, Kimitoshi; Kita, Kiyoshi; Tanaka, Saeko; Tabata, Kenta; Sekie, Kiyoteru; Yamamoto, Yorihiro; Sugiyama, Tomoyasu

    2015-12-01

    The freshwater planarian is a model organism used to study tissue regeneration that occupies an important position among multicellular organisms. Planarian genomic databases have led to the identification of genes that are required for regeneration, with implications for their roles in its underlying mechanism. Coenzyme Q (CoQ) is a fundamental lipophilic molecule that is synthesized and expressed in every cell of every organism. Furthermore, CoQ levels affect development, life span, disease and aging in nematodes and mice. Because CoQ can be ingested in food, it has been used in preventive nutrition. In this study, we investigated the role of CoQ in planarian regeneration. Planarians synthesize both CoQ9 and rhodoquinone 9 (RQ9). Knockdown of Smed-dlp1, a trans-prenyltransferase gene that encodes an enzyme that synthesizes the CoQ side chain, led to a decrease in CoQ9 and RQ9 levels. However, ATP levels did not consistently decrease in these animals. Knockdown animals exhibited tissue regression and curling. The number of mitotic cells decreased in Smed-dlp1 (RNAi) animals. These results suggested a failure in physiological cell turnover and stem cell function. Accordingly, regenerating planarians died from lysis or exhibited delayed regeneration. Interestingly, the observed phenotypes were partially rescued by ingesting food supplemented with α-tocopherol. Taken together, our results suggest that oxidative stress induced by reduced CoQ9 levels affects planarian regeneration and tissue homeostasis. PMID:26516985

  4. How Does The Bone Shaft Geometry Affect its Bending Properties?

    Directory of Open Access Journals (Sweden)

    Kaveh P. Saffar

    2009-01-01

    Full Text Available In this research, ten fresh specimens of sheep tibiae were provided from slaughtered animals. Whole bone specimens were loaded in three-point bending according to standard wet bone test protocols. Mechanical properties were determined and compared with the results which were obtained from two dry bone tests. The results showed that fracture bending moment and bone extrinsic stiffness had significant relations with fracture cross-section dependent parameters (i.e., cross-section area and area moment of inertia. Where, fracture energy and ultimate strength did not have such a relation with these parameters. Finite element modeling of bone shaft was made with simplified geometry (neglecting cross-section variations along bone shaft in two steps: First, by elliptical cross-section and second, by circular cross-section, assuming linear elastic and isotropic properties for the specimens. Elastic (Young’s modulus and fracture load, evaluated from curves obtained from tests, were applied to the finite element model and close results of maximum stress in both test specimen and first (elliptical cross-section model showed up. There was an average difference of about 2% between ultimate strength of wet bone specimens and maximum (tensile stress occurred in the elliptical models. However, this value for circular models was about 16%.

  5. Mechanisms of Intracellular Calcium Homeostasis in MC3T3-E1 Cells and Bone Tissues of Sprague-Dawley Rats Exposed to Fluoride.

    Science.gov (United States)

    Duan, Xiao-Qin; Li, Yan-Hui; Zhang, Xiu-Yun; Zhao, Zhi-Tao; Wang, Ying; Wang, Huan; Li, Guang-Sheng; Jing, Ling

    2016-04-01

    Calcium homeostasis of osteoblasts (OBs) has an important role in the physiology and pathology of bone tissue. In order to study the mechanisms of intracellular calcium homeostasis, MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, we examined intracellular-free calcium ion ([Ca(2+)]i) in MC3T3-E1 cells as well as mRNA and protein levels of Cav1.2, the main subunit of L-type voltage-dependent calcium channels (VDCCs), Na(+)/Ca(2+) exchange carriers (NCS), and plasma membrane Ca(2+)-ATPase (PMCA), inositol 1,4,5-trisphosphate receptor (IP3R) channels, sarco/endoplasmic reticulum calcium ATPase 2b (SERCA2b)/ATP2A2 in vitro, and rat bone tissues in vivo. Our results showed that [Ca(2+)]i of fluoride-treated OBs increased in a concentration-dependent manner with an increase in the concentration of fluoride. We also found that the low dose of fluoride led to high expression levels of Cav1.2, NCS-1, and PMCA and low expression levels of IP3R and SERCA2b/ATP2A2, while the high dose of fluoride induced an increase in SERCA2b/ATP2A2 levels and decrease in Cav1.2, PMCA, NCS-1, and IP3R levels. These results demonstrate that calcium channels and calcium pumps of plasma and endoplasmic reticulum (ER) membranes keep intracellular calcium homeostasis by regulating Cav1.2, NCS-1, PMCA, IP3R, and SERCA2b/ATP2A2 expression. PMID:26276564

  6. Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

    Science.gov (United States)

    Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

    2016-05-01

    The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. PMID:26944960

  7. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model.

    Science.gov (United States)

    Yingling, Vanessa R; Mitchell, Kathryn A; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is "a pediatric disease with geriatric consequences." Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  8. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    Science.gov (United States)

    Mitchell, Kathryn A.; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  9. Does aspiration of bones and joints affect results of later bone scanning

    International Nuclear Information System (INIS)

    To determine the effect, if any, of needle aspiration on /sup 99m/Tc bone scanning, three different areas of 15 dogs were first aspirated and then imaged with technetium bone scintigraphy. The hip joint was aspirated, the distal femoral metaphysis was drilled and aspirated, and the tibial periosteum was scraped with an 18- or 20-gauge needle. Varying amounts of trauma were inflicted to simulate varying difficulties at aspiration. /sup 99m/Tc bone scans were obtained from 5 h to 10 days later. There was no evidence of focal technetium uptake after any hip joint aspiration. This was consistent regardless of the amount of trauma inflicted or the time from aspiration to bone scanning. Metaphyseal cortical drilling and tibial periosteal scraping occasionally caused some focal uptake when scanning was delayed greater than 2 days. When osteomyelitis or pyarthrosis is clinically suspected, joint aspiration can be performed without fear of producing a false- positive bone scan

  10. Ocean acidification affects redox-balance and ion-homeostasis in the life-cycle stages of Emiliania huxleyi.

    Directory of Open Access Journals (Sweden)

    Sebastian D Rokitta

    Full Text Available Ocean Acidification (OA has been shown to affect photosynthesis and calcification in the coccolithophore Emiliania huxleyi, a cosmopolitan calcifier that significantly contributes to the regulation of the biological carbon pumps. Its non-calcifying, haploid life-cycle stage was found to be relatively unaffected by OA with respect to biomass production. Deeper insights into physiological key processes and their dependence on environmental factors are lacking, but are required to understand and possibly estimate the dynamics of carbon cycling in present and future oceans. Therefore, calcifying diploid and non-calcifying haploid cells were acclimated to present and future CO(2 partial pressures (pCO(2; 38.5 Pa vs. 101.3 Pa CO(2 under low and high light (50 vs. 300 µmol photons m(-2 s(-1. Comparative microarray-based transcriptome profiling was used to screen for the underlying cellular processes and allowed to follow up interpretations derived from physiological data. In the diplont, the observed increases in biomass production under OA are likely caused by stimulated production of glycoconjugates and lipids. The observed lowered calcification under OA can be attributed to impaired signal-transduction and ion-transport. The haplont utilizes distinct genes and metabolic pathways, reflecting the stage-specific usage of certain portions of the genome. With respect to functionality and energy-dependence, however, the transcriptomic OA-responses resemble those of the diplont. In both life-cycle stages, OA affects the cellular redox-state as a master regulator and thereby causes a metabolic shift from oxidative towards reductive pathways, which involves a reconstellation of carbon flux networks within and across compartments. Whereas signal transduction and ion-homeostasis appear equally OA-sensitive under both light intensities, the effects on carbon metabolism and light physiology are clearly modulated by light availability. These interactive effects

  11. Modifications of histamine receptor signaling affect bone mechanical properties in rats.

    Science.gov (United States)

    Folwarczna, Joanna; Janas, Aleksandra; Pytlik, Maria; Śliwiński, Leszek; Wiercigroch, Marek; Brzęczek, Anna

    2014-02-01

    Histamine receptors are expressed on bone cells and histamine may be involved in regulation of bone metabolism. The aim of the present study was to investigate the effects of loratadine (an H(1) receptor antagonist), ranitidine (an H(2) receptor antagonist) and betahistine (an H(3) receptor antagonist and H(1) receptor agonist) on bone mechanical properties in rats. Loratadine (5 mg/kg/day, po), ranitidine (50 mg/kg/day, po), or betahistine dihydrochloride (5 mg/kg/day, po), were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized (estrogen-deficient) 3-month-old rats, and their effects were compared with appropriate controls. Serum levels of bone turnover markers, bone mineralization and mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck were studied. In rats with normal estrogen level, administration of loratadine slightly favorably affected mechanical properties of compact bone, significantly increasing the strength of the femoral neck (p < 0.05), and tending to increase the strength of the femoral diaphysis. Ranitidine did not significantly affect the investigated parameters, and betahistine decreased the strength of the tibial metaphysis (cancellous bone, p < 0.01). There were no significant effects of the drugs on serum bone turnover markers. In estrogen-deficient rats, the drugs did not significantly affect the investigated skeletal parameters. In conclusion, the effects of histamine H(1), H(2) and H(3) receptor antagonists on the skeletal system in rats were differential and dependent on estrogen status. PMID:24905313

  12. Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization?

    DEFF Research Database (Denmark)

    Molgaard, C.; Larnkjaer, A.; Cashman, K.D.; Lamberg-Allardt, C.; Jakobsen, Jette; Michaelsen, K.F.

    2010-01-01

    VDR and ER genotype on the effect of the supplementation. Methods: The girls (n = 221) were randomized to receive either 5 mu g or 10 mu g vitamin D-3 supplementation per day or placebo for 12 months. Whole body and lumbar spine bone mass measured by DXA and pubertal status were determined at baseline...... density (BMD) (p = 0.007) and bone mineral content (BMC) (p = 0.048) in the FF VDR genotype but not in the Ff or ff VDR genotypes. Conclusion: Supplementation with vitamin D (5 or 10 mu g/day) over 12 months increased the S-25OHD concentration but there was no effect on indices of bone health in the...... entire group of girls. However, there was an effect on BMD for a subgroup with the FF VDR genotype indicating an influence of genotype....

  13. Peroxisomal Polyamine Oxidase and NADPH-Oxidase cross-talk for ROS homeostasis which affects respiration rate in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Efthimios A. Andronis

    2014-04-01

    Full Text Available Homeostasis of reactive oxygen species (ROS in the intracellular compartments is of critical importance as ROS have been linked with nearly all cellular processes and more importantly with diseases and aging. PAs are nitrogenous molecules with an evolutionary conserved role in the regulation of metabolic and energetic status of cells. Recent evidence also suggests that polyamines (PA are major regulators of ROS homeostasis. In Arabidopsis the backconversion of the PAs spermidine (Spd and spermine (Spm to putrescine (Put and Spd, respectively is catalyzed by two peroxisomal PA oxidases (AtPAO. However, the physiological role of this pathway remains largely elusive. Here we explore the role of peroxisomal PA backconversion and in particular that catalyzed by the highly expressed AtPAO3 in the regulation of ROS homeostasis and mitochondrial respiratory burst. Exogenous PAs exert an NADPH-oxidase dependent stimulation of oxygen consumption, with Spd exerting the strongest effect. This increase is attenuated by treatment with the NADPH-oxidase blocker diphenyleneiodonium iodide (DPI. Loss-of-function of AtPAO3 gene results to increased NADPH-oxidase-dependent production of superoxide anions (O2.-, but not H2O2, which activate the mitochondrial alternative oxidase pathway (AOX. On the contrary, overexpression of AtPAO3 results to an increased but balanced production of both H2O2 and O2.-. These results suggest that the ratio of O2.-/H2O2 regulates respiratory chain in mitochondria, with PA-dependent production of O2.- by NADPH-oxidase tilting the balance of electron transfer chain in favor of the AOX pathway. In addition, AtPAO3 seems to be an important component in the regulating module of ROS homeostasis, while a conserved role for PA backconversion and ROS across kingdoms is discussed.

  14. High Physiological Omega-3 Fatty Acid Supplementation Affects Muscle Fatty Acid Composition and Glucose and Insulin Homeostasis in Obese Adolescents

    OpenAIRE

    Frida Dangardt; Yun Chen; Eva Gronowitz; Jovanna Dahlgren; Peter Friberg; Birgitta Strandvik

    2012-01-01

    Obese adolescents have high concentrations of saturated fatty acids and low omega-3 long-chain polyunsaturated fatty acids (LCUFAs) in plasma phospholipids. We aimed to investigate effects of omega-3 LCPUFA supplementation to obese adolescents on skeletal muscle lipids and glucose and insulin homeostasis. Twenty-five obese adolescents (14–17 years old, 14 females) completed a randomized double-blind crossover study supplying capsules containing either 1.2 g omega-3 LCPUFAs or placebo, for 3 m...

  15. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits.

    Science.gov (United States)

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

    2014-02-01

    Odanacatib (ODN) is a bone resorption inhibitor which differs from standard antiresorptives by its ability to reduce bone resorption without decreasing bone formation. What is the reason for this difference? In contrast with other antiresorptives, such as alendronate (ALN), ODN targets only the very last step of the resorption process. We hypothesize that ODN may therefore modify the remodeling events immediately following osteoclastic resorption. These events belong to the reversal phase and include recruitment of osteoblasts, which is critical for connecting bone resorption to formation. We performed a histomorphometric study of trabecular remodeling in vertebrae of estrogen-deficient rabbits treated or not with ODN or ALN, a model where ODN, but not ALN, was previously shown to preserve bone formation. In line with our hypothesis, we found that ODN treatment compared to ALN results in a shorter reversal phase, faster initiation of osteoid deposition on the eroded surfaces, and higher osteoblast recruitment. The latter is reflected by higher densities of mature bone forming osteoblasts and an increased subpopulation of cuboidal osteoblasts. Furthermore, we found an increase in the interface between osteoclasts and surrounding osteoblast-lineage cells. This increase is expected to favor the osteoclast-osteoblast interactions required for bone formation. Regarding bone resorption itself, we show that ODN, but not ALN, treatment results in shallower resorption lacunae, a geometry favoring bone stiffness. We conclude that, compared to standard antiresorptives, ODN shows distinctive effects on resorption geometry and on reversal phase activities which positively affect osteoblast recruitment and may therefore favor bone formation. PMID:24085265

  16. NOS2 Is Critical to the Development of Emphysema in Sftpd Deficient Mice but Does Not Affect Surfactant Homeostasis

    OpenAIRE

    Knudsen, Lars; Atochina-Vasserman, Elena N.; GUO, CHANG-JIANG; Pamela A Scott; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

    2014-01-01

    Rationale Surfactant protein D (SP-D) has important immuno-modulatory properties. The absence of SP-D results in an inducible NO synthase (iNOS, coded by NOS2 gene) related chronic inflammation, development of emphysema-like pathophysiology and alterations of surfactant homeostasis. Objective In order to test the hypothesis that SP-D deficiency related abnormalities in pulmonary structure and function are a consequence of iNOS induced inflammation, we generated SP-D and iNOS double knockout m...

  17. NOS2 is critical to the development of emphysema in Sftpd deficient mice but does not affect surfactant homeostasis.

    Directory of Open Access Journals (Sweden)

    Lars Knudsen

    Full Text Available RATIONALE: Surfactant protein D (SP-D has important immuno-modulatory properties. The absence of SP-D results in an inducible NO synthase (iNOS, coded by NOS2 gene related chronic inflammation, development of emphysema-like pathophysiology and alterations of surfactant homeostasis. OBJECTIVE: In order to test the hypothesis that SP-D deficiency related abnormalities in pulmonary structure and function are a consequence of iNOS induced inflammation, we generated SP-D and iNOS double knockout mice (DiNOS. METHODS: Structural data obtained by design-based stereology to quantify the emphysema-like phenotype and disturbances of the intracellular surfactant were correlated to invasive pulmonary function tests and inflammatory markers including activation markers of alveolar macrophages and compared to SP-D (Sftpd(-/- and iNOS single knockout mice (NOS2(-/- as well as wild type (WT littermates. MEASUREMENTS AND RESULTS: DiNOS mice had reduced inflammatory cells in BAL and BAL-derived alveolar macrophages showed an increased expression of markers of an alternative activation as well as reduced inflammation. As evidenced by increased alveolar numbers and surface area, emphysematous changes were attenuated in DiNOS while disturbances of the surfactant system remained virtually unchanged. Sftpd(-/- demonstrated alterations of intrinsic mechanical properties of lung parenchyma as shown by reduced stiffness and resistance at its static limits, which could be corrected by additional ablation of NOS2 gene in DiNOS. CONCLUSION: iNOS related inflammation in the absence of SP-D is involved in the emphysematous remodeling leading to a loss of alveoli and associated alterations of elastic properties of lung parenchyma while disturbances of surfactant homeostasis are mediated by different mechanisms.

  18. Suture locking of isolated internal locking knotless suture anchors is not affected by bone quality

    Directory of Open Access Journals (Sweden)

    Woodmass JM

    2015-06-01

    Full Text Available Jarret M Woodmass,1 Graeme Matthewson,1 Yohei Ono,1,2 Aaron J Bois,1 Richard S Boorman,1 Ian KY Lo,1 Gail M Thornton1,31Department of Surgery, Section of Orthopaedic Surgery, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada; 2Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; 3Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada Purpose: The purpose of this study was to evaluate the mechanical performance of different suture locking mechanisms including: i interference fit between the anchor and the bone (eg, 4.5 mm PushLock, 5.5 mm SwiveLock, ii internal locking mechanism within the anchor itself (eg, 5.5 mm SpeedScrew, or iii a combination of interference fit and internal locking (eg, 4.5 mm MultiFIX P, 5.5 mm MultiFIX S. Methods: Anchors were tested in foam blocks representing normal (20/8 foam or osteopenic (8/8 foam bone, using standard suture loops pulled in-line with the anchor to isolate suture locking. Mechanical testing included cyclic testing for 500 cycles from 10 N to 60 N at 60 mm/min, followed by failure testing at 60 mm/min. Displacement after 500 cycles at 60 N, number of cycles at 3 mm displacement, load at 3 mm displacement, and maximum load were evaluated. Results: Comparing 8/8 foam to 20/8 foam, load at 3 mm displacement and maximum load were significantly decreased (P<0.05 with decreased bone quality for anchors that, even in part, relied on an interference fit suture locking mechanism (ie, 4.5 mm PushLock, 5.5 mm SwiveLock, 4.5 mm MultiFIX P, 5.5 mm MultiFIX S. Bone quality did not affect the mechanical performance of 5.5 mm SpeedScrew anchors which have an isolated internal locking mechanism. Conclusion: The mechanical performance of anchors that relied, even in part, on interference fit were affected by bone quality. Isolated internal locking knotless suture anchors functioned independently of bone quality

  19. Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis

    OpenAIRE

    Thaler, Roman; Sturmlechner, Ines; Spitzer, Silvia; Riester, Scott M; Rumpler, Monika; Zwerina, Jochen; Klaushofer, Klaus; van Wijnen, Andre J; Varga, Franz

    2014-01-01

    Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using ...

  20. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    Science.gov (United States)

    Litwak, Sara A; Loh, Kim; Stanley, William J; Pappas, Evan G; Wali, Jibran A; Selck, Claudia; Strasser, Andreas; Thomas, Helen E; Gurzov, Esteban N

    2016-01-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

  1. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    Peng Xia; Su Pan; Jieping Cheng; Maoguang Yang; Zhiping Qi; Tingting Hou; Xiaoyu Yang

    2014-01-01

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu-bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid-and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi-tol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro-tubule-associated protein 1B via a cross-signaling network, and affect the migratory efifciency of bone marrow mesenchymal stem cells towards injured spinal cord.

  2. Factors Affecting Detection Of Irradiated Bone Meat By Using Electron Spine Resonance

    International Nuclear Information System (INIS)

    Different types of bone meats were purchased locally such as camel, cow and sheep. The bones were removed, cleaned and irradiated with gamma rays at different doses (5, 10 and 20 kGy). The bone samples were stored in a refrigerator for five months for studying their stability of radiation-induced free radicals using electron spin resonance (ESR) technique. The effect of thermal treatment at 50oC at intervals was studied besides effect of storage period and re-irradiation process on ESR signal intensity. The ESR spectrum for radical species in irradiated samples was characterized by signal with spectroscopic splitting factor (g factor) of g1=2.0025 and g2=1.9973 for camel, cow and sheep bones, respectively. The signal at g = 2.0025 was ascribed to free radical rotation CO-2 that was derived from radiation-induced hydroxyapatite. Generally, the results proved that all above mentioned factors under investigation can affect ESR signal intensity but not prevent the recognize of irradiated bones, therefore, it must be taken in mind when calculating the absorbed dose.

  3. Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization.

    Science.gov (United States)

    Lu, Xuanyu; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla A; Diekwisch, Thomas Gh; Luan, Xianghong

    2016-06-01

    Matrix molecules such as the enamel-related calcium-binding phosphoprotein ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, and cartilage. Here we have asked whether AMBN is of functional importance for timely long bone development and, if so, how it exerts its function related to osteogenesis. Adolescent AMBN-deficient mice (AMBN(Δ5-6) ) suffered from a 33% to 38% reduction in femur length and an 8.4% shorter trunk spinal column when compared with WT controls, whereas there was no difference between adult animals. On a cellular level, AMBN truncation resulted in a shortened growth plate and a 41% to 49% reduction in the number of proliferating tibia chondrocytes and osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice displayed defects in proliferation and differentiation potential as well as cytoskeleton organization. Osteogenesis-related growth factors, such as insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the effect of AMBN on osteogenic growth factor and matrix protein gene expression. Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone growth, back-crossing of mutant mice with full-length AMBN overexpressors resulted in a complete rescue of AMBN(Δ5-6) bone defects. Together, these data indicate that AMBN affects extracellular matrix production and cell adhesion properties in the long bone growth plate, resulting in altered cytoskeletal dynamics, increased osteogenesis-related gene expression, as well as osteoblast and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone growth and an important growth spurt during the

  4. Bone: from a reservoir of minerals to a regulator of energy metabolism

    OpenAIRE

    Confavreux, Cyrille B.

    2011-01-01

    Besides locomotion, organ protection, and calcium–phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secret...

  5. Osmotic Homeostasis

    OpenAIRE

    Danziger, John; Zeidel, Mark L.

    2014-01-01

    Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal “osmoreceptors” that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water bala...

  6. Mutations in FAM20C Are Associated with Lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), Highlighting a Crucial Molecule in Bone Development

    OpenAIRE

    Simpson, M. A. ; Hsu, R. ; Keir, L. S. ; Hao, J. ; Sivapalan, G. ; Ernst, L. M. ; Zackai, E. H. ; Al-Gazali, L. I. ; Hulskamp, G. ; Kingston, H. M. ; Prescott, T. E. ; Ion, A. ; Patton, M. A. ; Murday, V. ; George, A. 

    2007-01-01

    The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies. Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or we...

  7. Short-term prolactin administration causes expressible galactorrhea but does not affect bone turnover: pilot data for a new lactation agent

    Directory of Open Access Journals (Sweden)

    Smith Patricia C

    2007-07-01

    Full Text Available Abstract Background Medications used to augment lactation increase prolactin secretion but can have intolerable side effects. We examined the biological activity of recombinant human prolactin (r-hPRL as preliminary data for its use to augment lactation. Methods Healthy, non-postpartum women (n = 21 with regular menstrual cycles underwent a seven day randomized, double-blind, placebo-controlled trial of r-hPRL. Expressible galactorrhea, markers of bone turnover, calcium homeostasis and gonadal function were measured and side effects recorded. Results Prolactin levels increased during r-hPRL administration (20.0 ± 2.8 to 231.7 ± 48.9 μg/L at 6 hours; p Conclusion In summary, r-hPRL can cause expressible galactorrhea. Seven days of r-hPRL administration does not adversely affect bone turnover or menstrual cyclicity. Thus, r-hPRL may be a viable option for short-term lactation augmentation. Trial registration Clinical Trials.gov NCT00438490

  8. Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice

    DEFF Research Database (Denmark)

    Tornvig, Lajla; Mosekilde, Leif; Justesen, J;

    2001-01-01

    Aging is associated with decreased trabecular bone mass and increased adipocyte formation in bone marrow. As osteoblasts and adipocytes share common precursor cells present in the bone marrow stroma, it has been proposed that an inverse relationship exists between adipocyte and osteoblast....../TV %) using the point-counting technique. Bone size did not differ between the two groups. In troglitazone-treated mice, AV/TV was significantly higher than in control mice (4.7+/-2.1% vs. 0.2+/-0.3%, respectively, mean +/- SD, P <0.001). BV/TV was similar in the two groups (16.9+/-5.6% for troglitazone...

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

    Science.gov (United States)

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

    2014-01-10

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

  10. Quinoa extract enriched in 20-hydroxyecdysone affects energy homeostasis and intestinal fat absorption in mice fed a high-fat diet.

    Science.gov (United States)

    Foucault, Anne-Sophie; Even, Patrick; Lafont, René; Dioh, Waly; Veillet, Stanislas; Tomé, Daniel; Huneau, Jean-François; Hermier, Dominique; Quignard-Boulangé, Annie

    2014-04-10

    In a previous study, we have demonstrated that a supplementation of a high-fat diet with a quinoa extract enriched in 20-hydroxyecdysone (QE) or pure 20-hydroxyecdysone (20E) could prevent the development of obesity. In line with the anti-obesity effect of QE, we used indirect calorimetry to examine the effect of dietary QE and 20E in high-fat fed mice on different components of energy metabolism. Mice were fed a high-fat (HF) diet with or without supplementation by QE or pure 20E for 3 weeks. As compared to mice maintained on a low-fat diet, HF feeding resulted in a marked physiological shift in energy homeostasis, associating a decrease in global energy expenditure (EE) and an increase in lipid utilization as assessed by the lower respiratory quotient (RQ). Supplementation with 20E increased energy expenditure while food intake and activity were not affected. Furthermore QE and 20E promoted a higher rate of glucose oxidation leading to an increased RQ value. In QE and 20E-treated HFD fed mice, there was an increase in fecal lipid excretion without any change in stool amount. Our study indicates that anti-obesity effect of QE can be explained by a global increase in energy expenditure, a shift in glucose metabolism towards oxidation to the detriment of lipogenesis and a decrease in dietary lipid absorption leading to reduced dietary lipid storage in adipose tissue. PMID:24534167

  11. Bone

    International Nuclear Information System (INIS)

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

  12. Interdental alveolar bone density in bruxers, mild bruxers, and non-bruxers affected by orthodontia and impaction as influencing factors.

    Directory of Open Access Journals (Sweden)

    Shereen Shokry

    2015-12-01

    Full Text Available Aim: To assess the interdental alveolar bone density within specific regions of interest in the mandible of bruxers, mild bruxers and non-bruxers in absence or presence of influencing factors, such as orthodontia and impaction. Materials and methods: The study consisted of 104 subjects (64 bruxers and 40 controls from the female students in the Faculty of Dentistry. Students were classified into bruxers, non-bruxers, and mild bruxers. The presence of modifying factors, such as impacted mandibular third molars and/or current or recent orthodontic treatment were identified. Panoramic radiographs were obtained, and the mean bone density values of interdental alveolar bone were measured using ImageJ software. Results: Non-bruxers had the highest mean bone density in all measured regions. The mesial aspect of the second premolar was an area of higher mean bone density in bruxers and in mild bruxers, compared to non-bruxers. In the presence of orthodontic treatment, the mean bone density in non-bruxers surpassed that of bruxers and mild bruxers. Conclusion: Bruxism, whether mild or severe decreased the interdental mean bone density in the studied regions of interest. The presence of influencing factors affected the interdental mean bone density.

  13. Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/β-Catenin Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Francesca Wannenes

    2014-01-01

    Full Text Available Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD. We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1 affected by obesity with normal BMD (O, (2 affected by obesity with low BMD (OO, (3 affected by obesity and sarcopenia (OS, and (4 affected by obesity, sarcopenia, and low BMD (OOS as compared to subjects with normal body weight and normal BMD (CTL. Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/β-catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered β-catenin cellular compartmentalization and GSK3β phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis.

  14. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    Science.gov (United States)

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-01-01

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active. PMID:26474791

  15. Cadmium affects viability of bone marrow mesenchymal stem cells through membrane impairment, intracellular calcium elevation and DNA breakage

    Directory of Open Access Journals (Sweden)

    Abnosi Mohammad Hussein

    2010-01-01

    Full Text Available Background: Cadmium is an important heavy metal with occupational and environmental hazard. Cadmium toxicity results mainly in bone-related complication such as itai-itai disease. Mesenchymal stem cells of the bone marrow have the ability to differentiate to osteoblasts which ensure the well-being of the bone tissue. Thus the aim was to investigate the effect of cadmium on viability of rat bone marrow mesenchymal stem cells. Materials and Methods: The rat bone marrow mesenchymal stem cells were grown to confluency in DMEM medium supplemented with 15% fetal bovine serum and penicillin-streptomycin up to third passage. Then the cells were treated with 0, 5, 15, 25, 35, and 45 of CdCl 2 at 12, 24, 36, and 48 h, and their viability was investigated using trypan blue staining. In addition, after treatment with selected dose (15 and 45 μM and time (24 and 48 h the cell morphology, DNA damage and calcium content of the cells were evaluated. Data was analyzed using one and two-way ANOVA (Tukey test and the P2+ was observed. Conclusion: Cadmium chloride is a toxic compound which might affect the well-being of bone tissue through affecting the mesenchymal stem cells.

  16. The Bone Resorption Inhibitors Odanacatib and Alendronate Affect Post-Osteoclastic Events Differently in Ovariectomized Rabbits

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L;

    2014-01-01

    Odanacatib (ODN) is a bone resorption inhibitor which differs from standard antiresorptives by its ability to reduce bone resorption without decreasing bone formation. What is the reason for this difference? In contrast with other antiresorptives, such as alendronate (ALN), ODN targets only the...

  17. New Insights into the Molecular Basis of Kidney Governing Bone Theory

    Institute of Scientific and Technical Information of China (English)

    Dong-feng Zhao; Yong-jian Zhao; Cheng-long Wang; Yan-ping Yang; Yong-jun Wang

    2015-01-01

    Kidney governing bone theory plays an important role in treating bone metabolic disease such as osteoporosis, and many tonifying kidney prescriptions/herbs are widely used in Traditional Chinese Medicine (TCM). However, the exact biological basis of kidney governing bone theory in the context of new advances in biology is still not fully established. In this paper, the content of kidney governing bone theory in biology has been fully demonstrated from different aspects. We first propose that bone and kidney mutually affect each other in pathology and physiology, particularly through homeostasis of calcium, phosphorus and fibroblast growth factor-23(FGF-23). Next, we identify that tonifying kidney prescriptions/herbs exert bone protective effects, thus treating osteoporosis by regulating bone formation and bone resorption. Furthermore, the exact molecular mechanisms of tonifying kidney prescriptions, herbs and their effective components in treating osteoporosis have been systematically reviewed. Finally, we come into the conclusion that kidney regulating bone mineral homeostasis, bone protective effects of tonifying kidney herbs and regulatory effects on bone homeostasis are all the manifestations of kidney governing bone theory. Therefore, the new insights into kidney governing bone theory in biology will promote the development of clinical practices, and drugs discovery in treating osteoporosis.

  18. Vascular homeostasis regulators, Edn1 and Agpt2, are upregulated as a protective effect of heat-treated zinc yeast in irradiated murine bone marrow

    International Nuclear Information System (INIS)

    The purpose of this study was to elucidate the mechanism underlying the in vivo radioprotection activity by Zn-containing, heat-treated Saccharomyces cerevisiae yeast (Zn-yeast). Zn-yeast suspension was administered into C3H/He mice immediately after whole body irradiation (WBI) at 7.5 Gy. Bone marrow was extracted from the mice 6 hours after irradiation and analyzed on a microarray. Expression changes in the candidate responsive genes differentially expressed in treated mice were re-examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The bone marrow was also examined pathologically at 6 h, 3, 7, and 14 days postirradiation. Thirty-six genes, including Edn1 and Agpt2, were identified as candidate responsive genes in irradiated mouse bone marrow treated with Zn-yeast by showing a greater than three-fold change compared with control (no irradiation and no Zn-yeast) mice. The expressions of Cdkn1a, Bax, and Ccng, which are well known as radioresponsive genes, were upregulated in WBI mice and Zn-yeast treated WBI mice. Pathological examination showed the newly formed microvessels lined with endothelial cells, and small round hematopoietic cells around vessels in bone marrow matrix of mice administered with Zn-yeast after WBI, while whole-body irradiated mice developed fatty bone marrow within 2 weeks after irradiation. This study identified a possible mechanism for the postirradiation protection conferred by Zn-yeast. The protective effect of Zn-yeast against WBI is related to maintaining the bone marrow microenvironment, including targeting endothelial cells and cytokine release. (author)

  19. The Bone Resorption Inhibitors Odanacatib and Alendronate Affect Post-Osteoclastic Events Differently in Ovariectomized Rabbits

    OpenAIRE

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

    2013-01-01

    Odanacatib (ODN) is a bone resorption inhibitor which differs from standard antiresorptives by its ability to reduce bone resorption without decreasing bone formation. What is the reason for this difference? In contrast with other antiresorptives, such as alendronate (ALN), ODN targets only the very last step of the resorption process. We hypothesize that ODN may therefore modify the remodeling events immediately following osteoclastic resorption. These events belong to the reversal phase and...

  20. Glutamate signalling in healthy and diseased bone

    Directory of Open Access Journals (Sweden)

    EricP.Seidlitz

    2012-07-01

    Full Text Available Bone relies on multiple extracellular signalling systems to maintain homeostasis of its normal structure and functions. The amino acid glutamate is a fundamental extracellular messenger molecule in many tissues, and is used in bone for both neural and non-neural signalling. This review focuses on the non-neural interactions, and examines the evolutionarily ancient glutamate signalling system in the context of its application to normal bone functioning and discusses recent findings on the role of glutamate signalling as they pertain to maintaining healthy bone structure. The underlying mechanisms of glutamate signalling and the many roles glutamate plays in modulating bone physiology are featured, including those involved in osteoclast and osteoblast differentiation and mature cell functions. Moreover, the relevance of glutamate signalling systems in diseases that affect bone, such as cancer and rheumatoid arthritis, is discussed, and will highlight how the glutamate system may be exploited as a viable therapeutic target. We will identify novel areas of research where knowledge of glutamate communication mechanisms may aid in our understanding of the complex nature of bone homeostasis. By uncovering the contributions of glutamate in maintaining healthy bone, the reader will discover how this complex molecular signalling system may advance our capacity to treat bone pathologies.

  1. Intravenous contrast injection significantly affects bone mineral density measured on CT

    Energy Technology Data Exchange (ETDEWEB)

    Pompe, Esther; Willemink, Martin J.; Dijkhuis, Gawein R.; Verhaar, Harald J.J.; Hoesein, Firdaus A.A.M.; Jong, Pim A. de [University Medical Center Utrecht, Department of Radiology and Internal Medicine-Geriatrics, Postbus 85500, Postbox: E.03.511, GA, Utrecht (Netherlands)

    2014-09-05

    The objective is to evaluate the effect of intravenous contrast media on bone mineral density (BMD) assessment by comparing unenhanced and contrast-enhanced computed tomography (CT) examinations performed for other indications. One hundred and fifty-two patients (99 without and 53 with malignant neoplasm) who underwent both unenhanced and two contrast-enhanced (arterial and portal venous phase) abdominal CT examinations in a single session between June 2011 and July 2013 were included. BMD was evaluated on the three examinations as CT-attenuation values in Hounsfield Units (HU) in the first lumbar vertebra (L1). CT-attenuation values were significantly higher in both contrast-enhanced phases, compared to the unenhanced phase (p < 0.01). In patients without malignancies, mean ± standard deviation (SD) HU-values increased from 128.8 ± 48.6 HU for the unenhanced phase to 142.3 ± 47.2 HU for the arterial phase and 147.0 ± 47.4 HU for the portal phase (p < 0.01). In patients with malignancies, HU-values increased from 112.1 ± 38.1 HU to 126.2 ± 38.4 HU and 130.1 ± 37.3 HU (p < 0.02), respectively. With different thresholds to define osteoporosis, measurements in the arterial and portal phase resulted in 7-25 % false negatives. Our study showed that intravenous contrast injection substantially affects BMD-assessment on CT and taking this into account may improve routine assessment of low BMD in nonquantitative CT. (orig.)

  2. Glucose homeostasis and metabolic adaptation in the pregnant and lactating sheep are affected by the level of nutrition previously provided during her late fetal life

    DEFF Research Database (Denmark)

    Husted, Sanne Munch; Nielsen, Mette Olaf; Blache, D;

    2008-01-01

    This study investigated whether undernutrition (UN) during late fetal life can programme the subsequent adult life adaptation of glucose homeostasis and metabolism during pregnancy and lactation. Twenty-four primiparous experimental ewes were used. Twelve had been exposed to a prenatal NORM level...... of nutrition (maternal diet approximately 15 MJME/d) and 12 to a LOW level of nutrition (maternal diet approximately 7 MJME/d) during the last 6 weeks pre-partum. The experimental ewes were subjected to two intravenous glucose tolerance tests (IGTT) in late gestation (one prior to (G-IGTT) and one by...

  3. Ethylene negatively regulates transcript abundance of ROP-GAP rheostat-encoding genes and affects apoplastic reactive oxygen species homeostasis in epicarps of cold stored apple fruits.

    Science.gov (United States)

    Zermiani, Monica; Zonin, Elisabetta; Nonis, Alberto; Begheldo, Maura; Ceccato, Luca; Vezzaro, Alice; Baldan, Barbara; Trentin, Annarita; Masi, Antonio; Pegoraro, Marco; Fadanelli, Livio; Teale, William; Palme, Klaus; Quintieri, Luigi; Ruperti, Benedetto

    2015-12-01

    Apple (Malus×domestica Borkh) fruits are stored for long periods of time at low temperatures (1 °C) leading to the occurrence of physiological disorders. 'Superficial scald' of Granny Smith apples, an economically important ethylene-dependent disorder, was used as a model to study relationships among ethylene action, the regulation of the ROP-GAP rheostat, and maintenance of H2O2 homeostasis in fruits during prolonged cold exposure. The ROP-GAP rheostat is a key module for adaptation to low oxygen in Arabidopsis through Respiratory Burst NADPH Oxidase Homologs (RBOH)-mediated and ROP GTPase-dependent regulation of reactive oxygen species (ROS) homeostasis. Here, it was shown that the transcriptional expression of several components of the apple ROP-GAP machinery, including genes encoding RBOHs, ROPs, and their ancillary proteins ROP-GEFs and ROP-GAPs, is coordinately and negatively regulated by ethylene in conjunction with the progressive impairment of apoplastic H2O2 homeostatic levels. RNA sequencing analyses showed that several components of the known ROP- and ROS-associated transcriptional networks are regulated along with the ROP-GAP rheostat in response to ethylene perception. These findings may extend the role of the ROP-GAP rheostat beyond hypoxic responses and suggest that it may be a functional regulatory node involved in the integration of ethylene and ROS signalling pathways in abiotic stress. PMID:26428066

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

    OpenAIRE

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

    2016-01-01

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

  5. Ageing and water homeostasis

    Science.gov (United States)

    Robertson, David; Jordan, Jens; Jacob, Giris; Ketch, Terry; Shannon, John R.; Biaggioni, Italo

    2002-01-01

    This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

  6. Hoof position during limb loading affects dorsoproximal bone strains on the equine proximal phalanx.

    Science.gov (United States)

    Singer, Ellen; Garcia, Tanya; Stover, Susan

    2015-07-16

    Sagittal fractures of the proximal phalanx (P1) in the racehorse appear to be associated with turf racing surfaces, which are known to restrict forward slide of the foot at impact. We hypothesized that restriction of forward foot slip would result in higher P1 bone strains during metacarpophalangeal joint (MCPJ) hyperextension. Unilateral limbs from six equine cadavers were instrumented with strain gauges and bone reference markers to measure dorsoproximal P1 bone strains and MCPJ extension, collateromotion and axial rotation during in vitro limb loading to 10,500 N. By limiting movement of the distal actuator platform, three different foot conditions (forward, free, and restricted) were applied in a randomised block design. Bone reference markers, recorded by video, were analyzed to determine motion of P1 relative to MC3. Rosette strain data were reduced to principal and shear magnitudes and directions. A mixed model ANOVA determined the effect of foot position on P1 bone strains and MCPJ angles. At 10,000 N load, the restricted condition resulted in higher P1 axial compressive (p=0.015), maximum shear (p=0.043) and engineering shear (p=0.046) strains compared to the forward condition. The restricted condition had higher compressive (p=0.025) and lower tensile (p=0.043) principal strains compared to the free condition. For the same magnitude of principal or shear strains, axial rotation and collateromotion angles were greatest for the restricted condition. Therefore, the increase in P1 principal compressive and shear bone strains associated with restricted foot slip indicate that alterations in foot:ground interaction may play a role in fracture occurrence in horses. PMID:26003484

  7. Anatomical aspects of posterior fossa affecting lateral suboccipital approach. Evaluation by bone-window CT

    International Nuclear Information System (INIS)

    The high-resolution 1.5 mm-slice bone-window CT images of the posterior fossa in 40 patients with the cerebello-pontine angle tumor were reviewed regarding three anatomical aspects: the internal occipital crest (IOC), the posterior surface of the petrous bone, and the 'petrous angle'. The IOC was sometimes prominent and protruded profoundly into the posterior fossa. The height of IOC from the inner table of the occipital bone was 9.6±3.3 mm. The posterior surface of the petrous bone was convex to the posterior fossa in the most cases; the zenith of the prominence was the porus acusticus. The convexity of the posterior surface in the CT image was objectively evaluated by the 'porus angle' made by two lines of A and B; the line A was the posterior half of the posterior surface of the petrous bone, and the line B was the anterior half of it. The 'porus angle' in 40 cases was 28±14deg in the left side, and 28±12deg in the right side. The 'petrous angle', made by the cranial sagittal line and (the posterior half of ) the posterior surface of the petrous bone, was 61.8±5.8deg and 62.7±7.0deg, respectively. In the patient with a prominent IOC, the lateral suboccipital approach (LSA) with a unilateral suboccipital craniotomy may induce the compression of the cerebellar hemisphere by the brain retractor and the prominent IOC, and develop cerebellar contusion. Such a postoperative cerebellar complication can be avoided by a large suboccipital craniotomy with the resection of the prominent IOC extending contralaterally. The severe convexity of the posterior surface of the petrous bone, i.e. the large 'porus angle', makes it difficult to get the view of the petroclival region in the LSA. The larger is the 'petrous angle', the less cerebellar compression is necessary for the approach to the cerebello-pontine angle by the LSA; the large 'petrous angle' is advantageous to the approach. (H.O.)

  8. Clinical relevance of the apparent diffusion coefficient value of metastatic bone tumours on diffusion-weighted MRI images: differences according to the types of primary tumour, the affected bones, and clinical factors

    International Nuclear Information System (INIS)

    Aim: To evaluate whether the apparent diffusion coefficient (ADC) of metastatic bone tumours on diffusion-weighted magnetic resonance imaging (MRI) images differs according to the type of primary cancer, the affected bone, and clinical factors. Materials and methods: For this retrospective study, two radiologists reviewed MRI images, including ADC maps, of 67 patients (M:F=38:29; median age, 48 years) who were diagnosed with bone metastasis by means of histological or clinical confirmation. The primary tumours included 29 lung adenocarcinomas, 15 invasive ductal adenocarcinomas of the breast, 13 hepatocellular carcinomas, six prostatic carcinomas, and four renal cell carcinomas. ADC values of the metastatic tumour were compared according to the type of primary malignancy, the affected bone, and the age and sex of the patient using Kruskal–Wallis and Mann–Whitney U-tests with Bonferroni correction. In addition, pre-contrast CT images were available in 38 of 67 patients; a subanalysis of the CT radiodensity and ADC values were performed with Spearman correlation. Results: The mean, standard deviation, and minimum and maximum values of the ADC of metastatic bone tumours did not differ significantly according to type of primary malignancy, the affected bone, or clinical variables (p>0.1). The ADC value was not significantly correlated with CT radiodensity (p=0.24). Intra- and interobserver agreements for the mean ADC values were excellent (intra-observer: p=0.98; interobserver: p=0.98). Conclusions: Assessment of the ADC value of metastatic bone tumours is not reliable for differentiation of the type of primary cancer. -- Highlights: •ADC of bone metastasis is not reliable for separation of the type of primary cancer. •ADC of bone metastasis does not differ according to the affected bone. •There is no significant correlation between ADC value and CT density

  9. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

    OpenAIRE

    Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

    2014-01-01

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubul...

  10. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Ippokratis Pountos

    2012-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients.

  11. Bone tumor

    Science.gov (United States)

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  12. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

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

  13. [Inflammation and bone : Osteoimmunological aspects].

    Science.gov (United States)

    Frommer, K W; Neumann, E; Lange, U

    2016-06-01

    Microscopic fractures (so-called microcracks) or traumatic macrofractures require bone, as the basic scaffold of the human body, to have a high regenerative capability. In order to be able to provide this regenerative capability, bone is in a constant process of remodeling. This finely tuned homeostasis of bone formation and degradation can become disrupted, which leads to osteoporosis or other bone disorders. It has been shown that the immune system is substantially involved in the regulation of bone homeostasis and that chronic inflammation in particular can disturb this balance; therefore, this article reviews the osteoimmunological aspects contributing to osteoporosis and other diseases associated with bone degradation. PMID:27250491

  14. Diabetes mellitus induces bone marrow microangiopathy

    OpenAIRE

    Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P. J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

    2009-01-01

    The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis.

  15. Carpal Tunnel Cross-Sectional Area Affected by Soft Tissues Abutting the Carpal Bones.

    Science.gov (United States)

    Gabra, Joseph N; Li, Zong-Ming

    2013-02-01

    The carpal tunnel accommodates free movement of its contents, and the tunnel's cross-sectional area is a useful morphological parameter for the evaluation of the space available for the carpal tunnel contents and of potential nerve compression in the tunnel. The osseous boundary of the carpal bones as the dorsal border of the carpal tunnel is commonly used to determine the tunnel area, but this boundary contains soft tissues such as numerous intercarpal ligaments and the flexor carpi radialis tendon. The aims of this study were to quantify the thickness of the soft tissues abutting the carpal bones and to investigate how this soft tissue influences the calculation of the carpal tunnel area. Magnetic resonance images were analyzed for eight cadaveric specimens. A medical balloon with a physiological pressure was inserted into an evacuated tunnel to identify the carpal tunnel boundary. The balloon-based (i.e. true carpal tunnel) and osseous-based carpal tunnel boundaries were extracted and divided into regions corresponding to the hamate, capitate, trapezoid, trapezium, and transverse carpal ligament (TCL). From the two boundaries, the overall and regional soft tissue thicknesses and areas were calculated. The soft tissue thickness was significantly greater for the trapezoid (3.1±1.2mm) and trapezium (3.4±1.0mm) regions than for the hamate (0.7±0.3mm) and capitate (1.2±0.5mm) regions. The carpal tunnel area using the osseous boundary (243.0±40.4mm(2)) was significantly larger than the balloon-based area (183.9±29.7mm(2)) with a ratio of 1.32. In other words, the carpal tunnel area can be estimated as 76% (= 1/1.32) of the osseous-based area. The abundance of soft tissue in the trapezoid and trapezium regions can be attributed mainly to the capitate-trapezium ligament and the flexor carpi radialis tendon. Inclusion of such soft tissue leads to overestimations of the carpal tunnel area. Correct quantification of the carpal tunnel area aids in examining carpal

  16. Glucocorticoid-Induced Changes in the Geometry of Osteoclast Resorption Cavities Affect Trabecular Bone Stiffness

    DEFF Research Database (Denmark)

    Vanderoost, Jef; Søe, Kent; Merrild, Ditte Marie Horslev;

    2012-01-01

    /BV, which is closely related to the shape of the cavities, highly determines the stiffness effect. The lumbar spine was the anatomic site most affected by the GC-induced changes on the shape of the cavities. These findings might explain the clinical observation that the prevalence of vertebral fractures...

  17. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    International Nuclear Information System (INIS)

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-κB activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or γ-glutamyl transpeptidase activity. Radiation activated NF-κB was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-κB activity, without toxicity to bone marrow, liver, and kidney

  18. Homeostasis in anorexia nervosa

    OpenAIRE

    Södersten, Per; Bergh, Cecilia; Zandian, Modjtaba; Ioakimidis, Ioannis

    2014-01-01

    Brainstem and hypothalamic “orexigenic/anorexigenic” networks are thought to maintain body weight homeostasis in response to hormonal and metabolic feedback from peripheral sites. This approach has not been successful in managing over- and underweight patients. It is suggested that concept of homeostasis has been misinterpreted; rather than exerting control, the brain permits eating in proportion to the amount of physical activity necessary to obtain food. In support, animal experiments have ...

  19. Homeostasis in anorexia nervosa

    OpenAIRE

    Per eSodersten; Cecilia eBergh; Modjtaba eZandian; Ioannis eIoakimidis

    2014-01-01

    Brainstem and hypothalamic orexigenic/anorexigenic networks are thought to maintain body weight homeostasis in response to hormonal and metabolic feedback from peripheral sites. This approach has not been successful in managing over- and underweight patients. It is suggested that concept of homeostasis has been misinterpreted; rather than exerting control, the brain permits eating in proportion to the amount of physical activity necessary to obtain food. In support, animal experiments have sh...

  20. Glucocorticoids affect the metabolism of bone marrow stromal cells and lead to osteonecrosis of the femoral head: a review

    Institute of Scientific and Technical Information of China (English)

    TAN Gang; KANG Peng-de; PEI Fu-xing

    2012-01-01

    Objective To review the recent developments in the mechanisms of glucocorticoids induced osteonecrosis of femoral head (ONFH) and introduce a new theory of ONFH.Data sources Both Chinese- and English-language literatures were searched using MEDLINE (1997-2011),Pubmed (1997-2011 ) and the Index of Chinese-language Literature (1997-2011 ).Study selection Data from published articles about mechanisms of glucocorticoids induced ONFH in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 61 articles which are listed in the reference section of this review.Results Glucocorticoids are steroid hormones secreted by the adrenal cortex that play a pivotal role in the regulation of a variety of developmental,metabolic and immune functions.However,high dose of exogenous glucocorticoids usage is the most common non-traumatic cause of ON FH.Glucocorticoids can affect the metabolisms of osteoblasts,osteoclasts,bone marrow stromal cells and adipocytes which decrease osteoblasts formation but increase adipocytes formation and cause ONFH finally.Conclusions Glucocorticoids affect the differentiation of mesenchymal stem cells,through activating or inhibiting the related transcript regulators of osteogenesis and adipogenesis.At last,the size and volume of mesenchymal stem cells derived adipocytes will increase amazingly,but the osteoblasts will be decreased obviously.In the meantime,the activity of the osteoclasts will be activated.So,these mechanisms work together and lead to ONFH.

  1. How do changes to plate thickness, length, and face-connectivity affect femoral cancellous bone's density and surface area? An investigation using regular cellular models.

    Science.gov (United States)

    Anderson, I A; Carman, J B

    2000-03-01

    Models of regular cellular-solids representing femoral head 'medial group' bone were used to (1) compare thickness data for plate-like and beam-like structures at realistic surface areas and densities; (2) test the validity of a standard formula for trabecular thickness (Tb.Th); and (3) study how systematic changes in cancellous bone thicknesses, spacing, and face-connectivity affect relative density and surface area. Models of different face-connectivities, produced by plate removal from the unit cell, were fitted to bone density and surface area data. The medial group bone was anisotropic: the supero-inferior (SI) direction was the principal direction for bone plate alignment and the plane normal to this had the largest number of bone/void intersections per unit line length (P(I)). A comparison of boundary perimeter per unit area data, in planes normal to SI, with surface area data placed the medial group bone between prismatic structures in which walls are parallel to one principal direction and isotropic structures. Selective removal of plates from a closed-cell model produced a similar result. For the same relative density and surface-area, plate-like models had significantly thinner cross-sections than beam-like models. The formula for Tb.Th produced overestimates of model plate thickness by up to 20% at realistic femoral cancellous densities. Trends in data on surface area to volume ratio and density observed on sampled medial group bone could be simulated by plate thickness changes on models of intermediate face-connectivity (approximately 1.5) or by plate removal from models with relatively thick and short (low aspect-ratio) plates. The latter mechanism is unrealistic for it resulted in beam-like structures at low 'medial group' densities, an architecture unlike the predominantly plate-like bone in the sample. PMID:10673116

  2. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    OpenAIRE

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can res...

  3. How Is Bone Cancer Diagnosed?

    Science.gov (United States)

    ... with bone cancer. Accurate diagnosis of a bone tumor often depends on combining information about its location (what bone is affected and even which part of the bone is involved), appearance on x-rays, and appearance under a microscope. ...

  4. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Science.gov (United States)

    Nguyen, Holly M; Ruppender, Nazanin; Zhang, Xiaotun; Brown, Lisha G; Gross, Ted S; Morrissey, Colm; Gulati, Roman; Vessella, Robert L; Schimmoller, Frauke; Aftab, Dana T; Corey, Eva

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. PMID:24205338

  5. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Directory of Open Access Journals (Sweden)

    Holly M Nguyen

    Full Text Available Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa, cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.

  6. Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture.

    Science.gov (United States)

    Lukas, Robin; Gigliotti, Joseph C; Smith, Brenda J; Altman, Stephanie; Tou, Janet C

    2011-09-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage. PMID:21672645

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

    OpenAIRE

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

    2010-01-01

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

  8. Cellular Homeostasis and Aging.

    Science.gov (United States)

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  9. Water Homeostasis: Evolutionary Medicine

    OpenAIRE

    Zeidel, Mark L.

    2012-01-01

    As a major component of homeostasis, all organisms regulate the water composition of various compartments. Through the selective use of barrier membranes and surface glycoproteins, as well as aquaporin water channels, organisms ranging from Archaebacteria to humans can vary water permeabilities across their cell membranes by 4 to 5 orders of magnitude. In barrier epithelia the outer, or exofacial, leaflet acts as the main resistor to water flow; this leaflet restricts water flow by minimizing...

  10. Effects of Adding Chymosin to Milk on Calcium Homeostasis

    DEFF Research Database (Denmark)

    Møller, Ulla Kristine; Jensen, Lars Thorbjørn; Mosekilde, Leif;

    2014-01-01

    Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome of the...

  11. Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

    OpenAIRE

    Nguyen, Holly M.; Nazanin Ruppender; Xiaotun Zhang; Lisha G. Brown; Gross, Ted S.; Colm Morrissey; Roman Gulati; Vessella, Robert L.; Frauke Schimmoller; Aftab, Dana T.; Eva Corey

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemis...

  12. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

    Science.gov (United States)

    Cox, Thomas R.; Rumney, Robin M.H.; Schoof, Erwin M.; Perryman, Lara; Høye, Anette M.; Agrawal, Ankita; Bird, Demelza; Latif, Norain Ab; Forrest, Hamish; Evans, Holly R.; Huggins, Iain D; Lang, Georgina; Linding, Rune

    2016-01-01

    Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia1. Tumour-secreted proteins play a crucial role in these interactions2–5 and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable6. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality6,7. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in ER-negative breast cancer patients. Global quantitative analysis of the hypoxic secretome identified Lysyl Oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis, independent of RANK Ligand, which disrupts normal bone homeostasis leading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonise and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications. PMID:26017313

  13. Supplementation with calcium and short-chain fructo-oligosaccharides affects markers of bone turnover but not bone mineral density in postmenopausal women.

    Science.gov (United States)

    Slevin, Mary M; Allsopp, Philip J; Magee, Pamela J; Bonham, Maxine P; Naughton, Violetta R; Strain, J J; Duffy, Maresa E; Wallace, Julie M; Mc Sorley, Emeir M

    2014-03-01

    This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444. PMID

  14. Weight loss on stimulant medication: how does it affect body composition and bone metabolism? – A prospective longitudinal study

    Directory of Open Access Journals (Sweden)

    Poulton Alison

    2012-12-01

    Full Text Available Abstract Objective Children treated with stimulant medication for attention deficit hyperactivity disorder (ADHD often lose weight. It is important to understand the implications of this during growth. This prospective study was designed to quantify the changes in body composition and markers of bone metabolism on starting treatment. Methods 34 children (29 boys aged 4.7 to 9.1 years newly diagnosed with ADHD were treated with dexamphetamine or methylphenidate, titrating the dose to optimise the therapeutic response. Medication was continued for as long as clinically indicated. Body composition and bone density (dual-energy X-ray absorptiometry were measured at baseline, 6 months and 3 years; changes were analysed in Z-scores based on data from 241 healthy, local children. Markers of bone turnover were measured at baseline, 3 months and 3 years. Results Fat loss of 1.4±0.96kg (total fat 5.7±3.6 to 4.3±3.1kg, p Conclusions Stimulant medication was associated with early fat loss and reduced bone turnover. Lean tissue including bone increased more slowly over 3 years of continuous treatment than would be expected for growth in height. There was long-term improvement in the proportion of central fat for height. This study shows that relatively minor reductions in weight on stimulant medication can be associated with long-term changes in body composition. Further study is required to determine the effects of these changes on adult health.

  15. Current socio-economic measures, and not those measured during infancy, affect bone mass in poor urban South african children.

    Science.gov (United States)

    Norris, Shane A; Sheppard, Zoë A; Griffiths, Paula L; Cameron, Noël; Pettifor, John M

    2008-09-01

    Understanding the impact of socio-economic status (SES) on physical development in children is important, especially in developing countries where considerable inequalities persist. This is the first study to examine the association between SES on bone development at the whole body, femoral neck, and lumbar spine in black children living in Soweto and Johannesburg, South Africa. Linear regression models were used to study associations between SES during infancy and current SES, anthropometric, and DXA-derived bone mass in 9/10-yr-old children (n = 309). Findings suggest that current SES measures, rather than SES during infancy, are stronger predictors of current whole body bone area (BA) and whole body BMC after adjusting for body size, pubertal development, physical activity, habitual dietary calcium intake, and body composition. SES had no significant effect on either hip or spine bone mass. Caregiver's marital/cohabiting status (indicator of social support) and whether there was a television in the home (indicator of greater income) at age 9/10 yr were the most important socio-economic determinants of whole body BA and BMC. SES has a significant independent effect on whole body BMC through its impact on BA. This suggests that poverty alleviation policies in South Africa could have a positive effect on bone health. PMID:18442310

  16. Bone and high-density lipoprotein: The beginning of a beautiful friendship.

    Science.gov (United States)

    Papachristou, Dionysios J; Blair, Harry C

    2016-02-18

    There is a tight link between bone and lipid metabolic pathways. In this vein, several studies focused on the exploration of high-density lipoprotein (HDL) in the pathobiology of bone diseases, with emphasis to the osteoarthritis (OA) and osteoporosis, the most common bone pathologies. Indeed, epidemiological and in vitro data have connected reduced HDL levels or dysfunctional HDL with cartilage destruction and OA development. Recent studies uncovered functional links between HDL and OA fueling the interesting hypothesis that OA could be a chronic element of the metabolic syndrome. Other studies have linked HDL to bone mineral density. Even though at epidemiological levels the results are conflicting, studies in animals as well as in vitro experiments have shown that HDL facilitates osteoblastogensis and bone synthesis and most probably affects osteoclastogenesis and osteoclast bone resorption. Notably, reduced HDL levels result in increased bone marrow adiposity affecting bone cells function. Unveiling the mechanisms that connect HDL and bone/cartilage homeostasis may contribute to the design of novel therapeutic agents for the improvement of bone and cartilage quality and thus for the treatment of related pathological conditions. PMID:26925377

  17. Homeostasis Hombre-Naturaleza

    Directory of Open Access Journals (Sweden)

    Stephano Betancourt

    2016-06-01

    Full Text Available La tendencia al equilibrio en la naturaleza y el flujo energético entre los organismos y suambiente; resulta de vital importancia para la supervivencia de estos últimos. Cuando seda una mirada antropocéntrica a esta interacción, se genera un enfoque reduccionista de losfactores que influyen para mantener la tendencia al equilibrio. Por consiguiente, el sostenerlo inteligible de las interacciones de los elementos que conforman nuestra existencia es unpunto clave de la compleja relación, entre el ser humano y su entorno, para poder permitiruna homeostasis entre ellos.

  18. Homeostasis in anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Per eSodersten

    2014-08-01

    Full Text Available Brainstem and hypothalamic orexigenic/anorexigenic networks are thought to maintain body weight homeostasis in response to hormonal and metabolic feedback from peripheral sites. This approach has not been successful in managing over- and underweight patients. It is suggested that concept of homeostasis has been misinterpreted; rather than exerting control, the brain permits eating in proportion to the amount of physical activity necessary to obtain food. In support, animal experiments have shown that while a hypothalamic orexigen excites eating when food is abundant, it inhibits eating and stimulates foraging when food is in short supply. As the physical price of food approaches zero, eating and body weight increase without constraints. Conversely, in anorexia nervosa body weight is homeostatically regulated, the high level of physical activity in anorexia is displaced hoarding for food that keeps body weight constantly low. A treatment based on this point of view, providing patients with computerized mealtime support to re-establish normal eating behavior, has brought 75% of patients with eating disorders into remission, reduced the rate of relapse to 10%, and eliminated mortality.

  19. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay;

    2015-01-01

    chronic kidney disease cohort. Methods: Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml...

  20. The Commensal Microbiota Drives Immune Homeostasis

    OpenAIRE

    Arrieta, Marie-Claire; Finlay, Barton Brett

    2012-01-01

    For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use t...

  1. Potential of proton microprobe for the analysis of normal and osteoporosis-affected compact bone. 1. Calcium-group and transition divalent metals

    International Nuclear Information System (INIS)

    Loss of mineral substances is the main characteristic of osteoporosis, and the goal of this study was to investigate those mineral elements, especially Ca and the divalent cation-forming metals. Proton microbeam IBA techniques (PIXE- Particle Induced X-ray Emission, PIGE-Particle Induced Gamma-ray Emission and PBS-Proton Backscattering) were applied to study the outer (∼1 mm) surface layer of bones, both healthy and affected by diabetes-associated osteoporosis, a topic that had been approached before by broad beam PIXE. We examined sections of femurs from healthy and experimentally diabetes-affected rats as well as tibia sections amputated from humans with osteoporosis-complicated diabetes; a healthy control bovine bone was also included. Most of the elements were analyzed by PIXE and a few by PIGE and PBS. The measurements were carried out at the Rossendorf nuclear microprobe with a 3.1 MeV proton beam focused to a ∼3-μm spot, using simultaneously three detectors. Element concentrations were determined by GUPIX calculations from the PIXE spectra. Most of the second main group elements were detected: Mg by PIGE and RBS, and Ca, Sr and Ba by PIXE. Divalent trace metals detected by PIXE included Cr, Mn, Fe, Ni, Cu, and Zn from the transition groups, as well as Pb (Cr, Fe, and Pb also occur in other oxidation states), but Cr, Mn and Cu were seen only in normal bones. A better spatial resolution for Fe, Zn, and Sr was obtained in mean line profiles of the number of counts normal to the surface. Thus near the outer surface of the bones, for most divalent metals the PIXE maps and profiles and the area concentrations showed features correlate to pathology, potentially relevant for a better understanding of osteoporosis mechanisms. (authors)

  2. Autophagy and intestinal homeostasis.

    Science.gov (United States)

    Patel, Khushbu K; Stappenbeck, Thaddeus S

    2013-01-01

    Nutrient absorption is the basic function that drives mammalian intestinal biology. To facilitate nutrient uptake, the host's epithelial barrier is composed of a single layer of cells. This constraint is problematic, as a design of this type can be easily disrupted. The solution during the course of evolution was to add numerous host defense mechanisms that can help prevent local and systemic infection. These mechanisms include specialized epithelial cells that produce a physiochemical barrier overlying the cellular barrier, robust and organized adaptive and innate immune cells, and the ability to mount an inflammatory response that is commensurate with a specific threat level. The autophagy pathway is a critical cellular process that strongly influences all these functions. Therefore, a fundamental understanding of the components of this pathway and their influence on inflammation, immunity, and barrier function will facilitate our understanding of homeostasis in the gastrointestinal tract. PMID:23216414

  3. The factors affecting outcome after non-vascular bone grafting and internal fixation for nonunion of the scaphoid.

    Science.gov (United States)

    Ramamurthy, C; Cutler, L; Nuttall, D; Simison, A J M; Trail, I A; Stanley, J K

    2007-05-01

    This study identified variables which influence the outcome of surgical management on 126 ununited scaphoid fractures managed by internal fixation and non-vascular bone grafting. The site of fracture was defined by a new method: the ratio of the length of the proximal fragment to the sum of the lengths of both fragments, calculated using specific views in the plain radiographs. Bone healing occurred in 71% (89) of cases. Only the site of nonunion (p = 1 x 10(-6)) and the delay to surgery (p = 0.001) remained significant on multivariate analysis. The effect of surgical delay on the probability of union increased as the fracture site moved proximally. A prediction model was produced by stepwise logistic regression analysis, enabling the surgeon to predict the success of surgery where the site of the nonunion and delay to surgery is known. PMID:17540748

  4. Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia.

    Science.gov (United States)

    Oliveri, M B; Wittich, A; Mautalen, C; Chaperon, A; Kizlansky, A

    2000-09-01

    Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/- 0.041 g/cm(2), P Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further. PMID:10954776

  5. Bone Health Should Be an Important Concern in the Care of Patients Affected by 21 Hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Dulon Jérome

    2010-09-01

    Full Text Available Osteoporosis has been an understandable concern for children and adult patients with congenital adrenal hyperplasia (CAH who may receive or have received supraphysiological doses of glucocorticoids. Some previous reports on bone mineral density (BMD in adult CAH patients showed no significant differences in BMD between patients with CAH and controls, but others have found lower BMD in CAH patients. In reports documenting the BMD reduction, this outcome has been attributed to an accumulated effect of prolonged exposure to excess glucocorticoids during infancy and childhood. We recently conducted a trial to establish the role of the total cumulative glucocorticoid dose on BMD. We established for the first time that there was a negative relationship between total cumulative glucocorticoid dose and lumbar and femoral BMD. Women might benefit from the preserving effect of estrogens compared to men. BMI (Body Mass Index also appeared to protect patients from bone loss. In light of this, physicians should bear in mind the potential consequences of glucocorticoids on bone and therefore adjust the treatment and improve clinical and biological surveillance from infancy. Furthermore, preventive measures against corticosteroid-induced osteoporosis should be discussed right from the beginning of glucocorticoid therapy.

  6. The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis

    Science.gov (United States)

    Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Kowalski, Artur; Rogala, Piotr; Strzyżewski, Wojciech; Łabędź, Wojciech; Uklejewski, Ryszard; Novotny, Karel; Kanicky, Viktor; Frankowski, Marcin

    2015-01-01

    The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID:26357659

  7. Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice.

    Science.gov (United States)

    Heveran, Chelsea M; Ortega, Alicia M; Cureton, Andrew; Clark, Ryan; Livingston, Eric W; Bateman, Ted A; Levi, Moshe; King, Karen B; Ferguson, Virginia L

    2016-05-01

    Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week-old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60μm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD. PMID:26860048

  8. BONE IN OSTEOPETROSIS

    Directory of Open Access Journals (Sweden)

    Ramkumar

    2014-04-01

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

  9. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    Directory of Open Access Journals (Sweden)

    Paola Maroni

    2016-03-01

    Full Text Available Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination.

  10. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages.

    Science.gov (United States)

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  11. Retinoic acid differentially affects in vitro proliferation, differentiation and mineralization of two fish bone-derived cell lines: different gene expression of nuclear receptors and ECM proteins.

    Science.gov (United States)

    Fernández, Ignacio; Tiago, Daniel M; Laizé, Vincent; Leonor Cancela, M; Gisbert, Enric

    2014-03-01

    Retinoic acid (RA), the main active metabolite of vitamin A, regulates vertebrate morphogenesis through signaling pathways not yet fully understood. Such process involves the specific activation of retinoic acid and retinoid X receptors (RARs and RXRs), which are nuclear receptors of the steroid/thyroid hormone receptor superfamily. Teleost fish are suitable models to study vertebrate development, such as skeletogenesis. Cell systems capable of in vitro mineralization have been developed for several fish species and may provide new insights into the specific cellular and molecular events related to vitamin A activity in bone, complementary to in vivo studies. This work aims at investigating the in vitro effects of RA (0.5 and 12.5 μM) on proliferation, differentiation and extracellular matrix (ECM) mineralization of two gilthead seabream bone-derived cell lines (VSa13 and VSa16), and at identifying molecular targets of its action through gene expression analysis. RA induced phenotypic changes and cellular proliferation was inhibited in both cell lines in a cell type-dependent manner (36-59% in VSa13 and 17-46% in VSa16 cells). While RA stimulated mineral deposition in VSa13 cell cultures (50-62% stimulation), it inhibited the mineralization of extracellular matrix in VSa16 cells (11-57% inhibition). Expression of hormone receptor genes (rars and rxrs), and extracellular matrix-related genes such as matrix and bone Gla proteins (mgp and bglap), osteopontin (spp1) and type I collagen (col1a1) were differentially regulated upon exposure to RA in proliferating, differentiating and mineralizing cultures of VSa13 and VSa16 cells. Altogether, our results show: (i) RA affects proliferative and mineralogenic activities in two fish skeletal cell types and (ii) that during phenotype transitions, specific RA nuclear receptors and bone-related genes are differentially expressed in a cell type-dependent manner. PMID:24291400

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

    Science.gov (United States)

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

    2014-03-01

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

  13. EPIDEMIOLOGICAL STUDY ON THE IMPLANT TREATMENT NEEDS IN CASES OF BONE AFFECTION IN PATIENTS WITH PERIODONTAL DISEASES

    Directory of Open Access Journals (Sweden)

    Diana Paula Radu

    2012-09-01

    Full Text Available The scope of the study is to critically evaluate and, implicitly, to establish a correlation among the status of edentation, the missing odonto-periodontal support and the necessary implantary therapy. Materials and method: The experimental group was formed of 179 patients, 93 women and 86 men, with ages between 18 and 72 years, who addressed the Clinics of Periodontology and some private consulting room between 2010-2012. The investigations involved both a minute clinical examination, by descriptive and canonic methods, and paraclinical exams: gnatophotostatic examinations on intra- and extra-oral (front and profile photos, patterns of study and radiological evaluation by OPT with markers. Results and discussion: The highest values were registered for III class Kennedy edentations, especially in the 31-50 years group of age, and mainly in women. This evaluation led to a higher number of implantary treatments. The necessary of implantary treatments was of 100% in IV, V and VI class Kennedy edentations, as well as in total edentations. Conclusions: The necessary number of interventions on bone structures for the optimization of the implantary field is of 43.92%, the highest ratios being represented by controlled bone regeneration.

  14. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

    Directory of Open Access Journals (Sweden)

    Emma L Duncan

    2011-04-01

    Full Text Available Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years, with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900, with replication in cohorts of women drawn from the general population (n = 20,898. The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

  15. Further studies on the intermediary metabolism of bone in vitro and a monoclonal cell line (MMB-1) derived from bone: effects of parathyroid hormone and acetazolamide

    International Nuclear Information System (INIS)

    The mechanism/mechanisms by which PTH affects Ca homeostasis between blood and bone have not been clearly established. Most studies of metabolic acid production in bone took place during the late 1950s and early 1960s. Since that time, assay techniques for metabolic acid production have been improved for greater sensitivity, more has been learned as to how PTH mediates its cellular responses, and techniques for cell isolation and culture have dramatically improved. These improvements have made possible new approaches to the study of short term effects of PTH on metabolic acid production in bone. Chapter 1 explores the potential of bone to utilize substrates other than glucose for metabolic energy transfer. Chapter 2 characterizes glucose metabolism in mouse calvaria in vitro and explores effects of PTH, acetazolamide, and C1 13,850 on calvaria oxidative metabolism. Chapter 3 describes PTH effects on glucose metabolism of MMB-1 cells, a monoclonal cell line reported to possess osteoblast-like characteristics

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

    Science.gov (United States)

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

    2016-08-01

    Due to older people's low sports participation rates, exercise frequency may be the most critical component for designing exercise protocols that address bone. The aims of the present article were to determine the independent effect of exercise frequency (ExFreq) and its corresponding changes on bone mineral density (BMD) and to identify the minimum effective dose that just relevantly affects bone. Based on the 16-year follow-up of the intense, consistently supervised Erlangen Fitness and Osteoporosis Prevention-Study, ExFreq was retrospectively determined in the exercise-group of 55 initially early-postmenopausal females with osteopenia. Linear mixed-effect regression analysis was conducted to determine the independent effect of ExFreq on BMD changes at lumbar spine and total hip. Minimum effective dose of ExFreq based on BMD changes less than the 90% quantile of the sedentary control-group (n=43). Cut-offs were determined after 4, 8, 12 and 16years using bootstrap with 5000 replications. After 16years, average ExFreq ranged between 1.02 and 2.96sessions/week (2.28±0.40sessions/week). ExFreq has an independent effect on LS-BMD (p<.001) and hip-BMD (p=.005) changes. Bootstrap analysis detected a minimum effective dose at about 2sessions/week/16years (cut-off LS-BMD: 2.11, 95% CI: 2.06-2.12; total hip-BMD: 2.22, 95% CI: 2.00-2.78sessions/week/16years). In summary, the minimum effective dose of exercise frequency that relevantly addresses BMD is quite high, at least compared with the low sport participation rate of older adults. This result might not be generalizable across all exercise types, protocols and cohorts, but it does indicate at least that even when applying high impact/high intensity programs, exercise frequency and its maintenance play a key role in bone adaptation. PMID:27108341

  17. Urinary calcium and oxalate excretion in healthy adult cats are not affected by increasing dietary levels of bone meal in a canned diet.

    Directory of Open Access Journals (Sweden)

    Nadine Passlack

    Full Text Available This study aimed to investigate the impact of dietary calcium (Ca and phosphorus (P, derived from bone meal, on the feline urine composition and the urinary pH, allowing a risk assessment for the formation of calcium oxalate (CaOx uroliths in cats. Eight healthy adult cats received 3 canned diets, containing 12.2 (A, 18.5 (B and 27.0 g Ca/kg dry matter (C and 16.1 (A, 17.6 (B and 21.1 g P/kg dry matter (C. Each diet was fed over 17 days. After a 7 dayś adaptation period, urine and faeces were collected over 2×4 days (with a two-day rest between, and blood samples were taken. Urinary and faecal minerals, urinary oxalate (Ox, the urinary pH and the concentrations of serum Ca, phosphate and parathyroid hormone (PTH were analyzed. Moreover, the urine was microscopically examined for CaOx uroliths. The results demonstrated that increasing levels of dietary Ca led to decreased serum PTH and Ca and increased faecal Ca and P concentrations, but did not affect the urinary Ca or Ox concentrations or the urinary fasting pH. The urinary postprandial pH slightly increased when the diet C was compared to the diet B. No CaOx crystals were detected in the urine of the cats. In conclusion, urinary Ca excretion in cats seems to be widely independent of the dietary Ca levels when Ca is added as bone meal to a typical canned diet, implicating that raw materials with higher contents of bones are of subordinate importance as risk factors for the formation of urinary CaOx crystals.

  18. Bone tumor

    Science.gov (United States)

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

  19. Bone Grafts

    Science.gov (United States)

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

  20. Basketball Affects Bone Mineral Density Accrual in Boys More Than Swimming and Other Impact Sports: 9-mo Follow-Up.

    Science.gov (United States)

    Agostinete, Ricardo R; Lynch, Kyle R; Gobbo, Luís A; Lima, Manoel Carlos Spiguel; Ito, Igor H; Luiz-de-Marco, Rafael; Rodrigues-Junior, Mario A; Fernandes, Romulo A

    2016-01-01

    The objective of this study was to analyze the effect of different sports on bone mineral density (BMD) accrual among male adolescents during a 9-mo follow-up. The sample was composed of 82 boys (control [n = 13], basketball [n = 14], karate [n = 9], soccer [n = 18], judo [n = 12], and swimming [n = 16]) who were followed up for 9 mo (from October 2013 to August 2014). BMD (gram per square centimeter) was assessed at baseline and follow-up using a dual-energy X-ray absorptiometry scanner, whereas somatic maturation was estimated through the use of the peak height velocity. Vitamin D consumption was assessed by questionnaire. After 9 mo of follow-up, all groups (including the control group) presented significant BMD accrual (overall sample: 4.5% in the whole body). On the other hand, the basketball group presented higher BMD accrual in the upper limbs (17.6%) than the control group (7.2%). A similar difference was observed in whole-body BMD (control group: 4.1% vs basketball group: 7.1%). The basketball group had significantly higher BMD gains than the control group and other sports groups. PMID:27174316

  1. Epididymis cholesterol homeostasis and sperm fertilizing ability

    Institute of Scientific and Technical Information of China (English)

    Fabrice Saez; Aurélia Ouvrier; Jo(e)l R Drevet

    2011-01-01

    Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

  2. From bone to breast and back - the bone cytokine RANKL and breast cancer

    OpenAIRE

    Hofbauer, Lorenz C; Rachner, Tilman D; Hamann, Christine

    2011-01-01

    Receptor activator of nuclear factor-κB ligand (RANKL) plays a pivotal role in regulating bone homeostasis. Osteoporosis and malignant bone disease secondary to breast cancer are characterized by enhanced RANKL production and increased bone turnover. Thus, denosumab, a monoclonal antibody to RANKL, has been developed and is now approved for various bone loss conditions. Recent results indicate that RANKL may also promote the development and osseous migration of breast cancer.

  3. Homeostasis of T Cell Diversity

    Institute of Scientific and Technical Information of China (English)

    Vinay S. Mahajan; Ilya B. Leskov; Jianzhu Chen

    2005-01-01

    T cell homeostasis commonly refers to the maintenance of relatively stable T cell numbers in the peripheral lymphoid organs. Among the large numbers of T cells in the periphery, T cells exhibit structural diversity, I.e., the expression of a diverse repertoire of T cell receptors (TCRs), and functional diversity, I.e., the presence of T cells at na(I)ve, effector, and memory developmental stages. Although the homeostasis of T cell numbers has been extensively studied, investigation of the mechanisms underlying the maintenance of structural and functional diversity of T cells is still at an early stage. The fundamental feature throughout T cell development is the interaction between the TCR and either self or foreign peptides in association with MHC molecules. In this review, we present evidence showing that homeostasis of T cell number and diversity is mediated through competition for limiting resources.The number of T cells is maintained through competition for limiting cytokines, whereas the diversity of T cells is maintained by competition for self-peptide-MHC complexes. In other words, diversity of the self-peptide repertoire limits the structural (TCR) diversity of a T cell population. We speculate that cognate low affinity self-peptides,acting as weak agonists and antagonists, regulate the homeostasis of T cell diversity whereas non-cognate or null peptides which are extremely abundant for any given TCR, may contribute to the homeostasis of T cell number by providing survival signals. Moreover, self-peptides and cytokines may form specialized niches for the regulation of T cell homeostasis.

  4. Homeostasis of T Cell Diversity

    Institute of Scientific and Technical Information of China (English)

    VinayS.Mahajan; IlyaB.Leskov; JianzhuChen

    2005-01-01

    T cell homeostasis commonly refers to the maintenance of relatively stable T cell numbers in the peripheral lymphoid organs. Among the large numbers of T cells in the periphery, T cells exhibit structural diversity, i.e., the expression of a diverse repertoire of T cell receptors (TCRs), and functional diversity, i.e., the presence of T cells at naive, effector, and memory developmental stages. Although the homeostasis of T cell numbers has been extensively studied, investigation of the mechanisms underlying the maintenance of structural and functional diversity of T cells is still at an early stage. The fundamental feature throughout T cell development is the interaction between the TCR and either self or foreign peptides in association with MHC molecules. In this review, we present evidence showing that homeostasis of T cell number and diversity is mediated through competition for limiting resources. The number of T cells is maintained through competition for limiting cytokines, whereas the diversity of T cells is maintained by competition for self-peptide-MHC complexes. In other words, diversity of the self-peptide repertoire limits the structural (TCR) diversity of a T cell population. We speculate that cognate low affinity self-peptides, acting as weak agonists and antagonists, regulate the homeostasis of T cell diversity whereas non-cognate or null peptides which are extremely abundant for any given TCR, may contribute to the homeostasis of T cell number by providing survival signals. Moreover, self-peptides and cytokines may form specialized niches for the regulation of T cell homeostasis. Cellular & Molecular Immunology. 2005;2(1): 1-10.

  5. The Hedgehog signalling pathway in bone formation

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  6. Leptin and Hormones: Energy Homeostasis.

    Science.gov (United States)

    Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

    2016-09-01

    Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. PMID:27519135

  7. Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

    OpenAIRE

    2015-01-01

    Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteopr...

  8. Wnt Signaling in Bone

    Science.gov (United States)

    Kubota, Takuo; Michigami, Toshimi; Ozono, Keiichi

    2010-01-01

    Wnt signaling is involved not only in embryonic development but also in maintenance of homeostasis in postnatal tissues. Multiple lines of evidence have increased understanding of the roles of Wnt signaling in bone since mutations in the LRP5 gene were identified in human bone diseases. Canonical Wnt signaling promotes mesenchymal progenitor cells to differentiate into osteoblasts. The canonical Wnt/β-catenin pathway possibly through Lrp6, a co-receptor for Wnts as well as Lrp5, in osteoblasts regulates bone resorption by increasing the OPG/RANKL ratio. However, endogenous inhibitors of Wnt signaling including sclerostin block bone formation. Regulation of sclerostin appears to be one of the mechanisms of PTH anabolic actions on bone. Since sclerostin is almost exclusively expressed in osteocytes, inhibition of sclerostin is the most promising design. Surprisingly, Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum, but not by directly promoting bone formation. Pharmacological intervention may be considered in many components of the canonical Wnt signaling pathway, although adverse effects and tumorigenicity to other tissues are important. More studies will be needed to fully understand how the Wnt signaling pathway actually influences bone metabolism and to assure the safety of new interventions. PMID:23926379

  9. Perturbed cholesterol homeostasis in aging spinal cord.

    Science.gov (United States)

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2016-09-01

    The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging. PMID:27459933

  10. Air pollution and genetic influences on bone mineral density and osteoporosis

    Directory of Open Access Journals (Sweden)

    Mariana CEVEI

    2010-05-01

    Full Text Available Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density, disrupted bone microarchitecture and alterations in the amount and variety of proteins in bones. Bone turnover is a very complex process, depending on genetic and non genetic factors, such as diet, lifestyle or air pollution. The aim of the study was to explore genetic and environmental risk factors that contribute to osteoporosis by quantifying several factors related to bone mineral density. We assessed family history, vitamin D status, bone mineral density in subjects seeking advice on osteoporosis. Air pollution data were also obtained. Average concentrations of NO2 and particulate matter PM10 were calculated. Due to their synergistic effect on the organism the maximum permissible concentration calculated for all air pollutants was exceeded. In our study total body bone mineral density was inversely associated with indicators of air pollution. The prevalence of vitamin D depletion was 64.76%. Genetic contribution to the etiology of osteoporosis was revealed by the positive family history for 36% affected subjects. Air pollution and vitamin D deficiency have a negative impact on bone mineral homeostasis.

  11. Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy.

    Science.gov (United States)

    Hartmann, Kerstin; Koenen, Mascha; Schauer, Sebastian; Wittig-Blaich, Stephanie; Ahmad, Mubashir; Baschant, Ulrike; Tuckermann, Jan P

    2016-04-01

    Cartilage and bone are severely affected by glucocorticoids (GCs), steroid hormones that are frequently used to treat inflammatory diseases. Major complications associated with long-term steroid therapy include impairment of cartilaginous bone growth and GC-induced osteoporosis. Particularly in arthritis, GC application can increase joint and bone damage. Contrarily, endogenous GC release supports cartilage and bone integrity. In the last decade, substantial progress in the understanding of the molecular mechanisms of GC action has been gained through genome-wide binding studies of the GC receptor. These genomic approaches have revolutionized our understanding of gene regulation by ligand-induced transcription factors in general. Furthermore, specific inactivation of GC signaling and the GC receptor in bone and cartilage cells of rodent models has enabled the cell-specific effects of GCs in normal tissue homeostasis, inflammatory bone diseases, and GC-induced osteoporosis to be dissected. In this review, we summarize the current view of GC action in cartilage and bone. We further discuss future research directions in the context of new concepts for optimized steroid therapies with less detrimental effects on bone. PMID:26842265

  12. Bone Biopsy

    Science.gov (United States)

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

  13. Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant

    International Nuclear Information System (INIS)

    Purpose: To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). Methods and Materials: Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. Results: At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first

  14. Nitric oxide and plant iron homeostasis.

    Science.gov (United States)

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. PMID:25612116

  15. RANKL, osteopontin, and osteoclast homeostasis in a hyperocclusion mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Cameron G.; Ito, Yoshihiro; Dangaria, Smit; Luan, Xianghong; Diekwisch, Thomas G.H. (UIC)

    2009-10-21

    The biological mechanisms that maintain the position of teeth in their sockets establish a dynamic equilibrium between bone resorption and apposition. In order to reveal some of the dynamics involved in the tissue responses towards occlusal forces on periodontal ligament (PDL) and alveolar bone homeostasis, we developed the first mouse model of hyperocclusion. Swiss-Webster mice were kept in hyperocclusion for 0, 3, 6, and 9 d. Morphological and histological changes in the periodontium were assessed using micro-computed tomography (micro-CT) and ground sections with fluorescent detection of vital dye labels. Sections were stained for tartrate-resistant acid phosphatase, and the expression of receptor activator of nuclear factor-{kappa}B ligand (RANKL) and osteopontin (OPN) was analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). Traumatic occlusion resulted in enamel surface abrasion, inhibition of alveolar bone apposition, significant formation of osteoclasts at 3, 6 and 9 d, and upregulation of OPN and RANKL. Data from this study suggest that both OPN and RANKL contribute to the stimulation of bone resorption in the hyperocclusive state. In addition, we propose that the inhibition of alveolar bone apposition by occlusal forces is an important mechanism for the control of occlusal height that might work in synergy with RANKL-induced bone resorption to maintain normal occlusion.

  16. Bone densitometer

    International Nuclear Information System (INIS)

    In an x-ray bone densitometer, special calibration techniques are employed to accommodate variations. In one aspect, a bone-like calibration material is interposed and the system determines the calibration data from rays passing only through flesh. In another aspect, a rotating device carries the calibration material through the beam. The specific densitometer shown uses an x-ray tube operated at two different voltages to generate a pencil beam, the energy levels of the x-ray photons being a function of the voltage applied. An integrating detector is timed to integrate the detected signal of the patient-attenuated beam over each pulse, the signals are converted to digital values and a digital computer converts the set of values produced by the raster scan into a representation of the bone density of the patient. Multiple reference detectors with differing absorbers are used by the system to continuously correct for variation in voltage and current of the x-ray tube. Calibration is accomplished by the digital computer on the basis of passing the pencil beam through known bone-representing substance as the densitometer scans portions of the patient having bone and adjacent portions having only flesh. A set of detected signals affected by the calibration substance in regions having only flesh is compared by the computer with a set of detected signals unaffected by the calibration material

  17. Neurohypophyseal hormones: novel actors of striated muscle development and homeostasis

    Directory of Open Access Journals (Sweden)

    Alessandra Costa

    2014-09-01

    Full Text Available Since the 1980's, novel functional roles of the neurohypophyseal hormones vasopressin and oxytocin have emerged. Several studies have investigated the effects of these two neurohormones on striated muscle tissues, both in vitro and in vivo. The effects of vasopressin on skeletal myogenic cells, developing muscle and muscle homeostasis have been documented. Oxytocin appears to have a greater influence on cardiomyocite differentiation and heart homeostasis. This review summarizes the studies on these novel roles of the two neurohypophyseal hormones, and open the possibility of new therapeutic approaches for diseases affecting striated muscle.

  18. Conditional deletion of cytochrome p450 reductase in osteoprogenitor cells affects long bone and skull development in mice recapitulating antley-bixler syndrome: role of a redox enzyme in development.

    Directory of Open Access Journals (Sweden)

    Satya P Panda

    Full Text Available NADPH-cytochrome P450 oxidoreductase (POR is the primary electron donor for cytochromes P450, dehydrocholesterol reductase, heme oxygenase, and squalene monooxygenase. Human patients with specific mutations in POR exhibit severe developmental malformations including disordered steroidogenesis, sexual ambiguities and various bone defects, similar to those seen in patients with Antley-Bixler syndrome (ABS. To probe the role of POR during bone development, we generated a conditional knockout mouse (CKO by cross breeding Por (lox/lox and Dermo1 Cre mice. CKO mice were smaller than their littermate controls and exhibited significant craniofacial and long bone abnormalities. Differential staining of the CKO mice skull bases shows premature fusion of the sphenooccipital and basioccipital-exoccipital synchondroses. Class III malocclusion was noted in adult knockout mice with an unusual overgrowth of the lower incisors. Shorter long bones were observed along with a reduction in the bone volume fraction, measured by microCT, in the Por-deleted mice compared to age- and sex-matched littermate controls. Concerted up- or down-regulation of proteins in the FGF signaling pathway observed by immunohistochemistry in the tibia samples of CKO mice compared to wild type controls shows a decrease in the FGF signaling pathway. To our knowledge, this is the first report of a mouse model that recapitulates both skull and long bone defects upon Por deletion, offering an approach to study the sequelae of POR mutations. This unique model demonstrates that P450 metabolism in bone itself is potentially important for proper bone development, and that an apparent link exists between the POR and FGF signaling pathways, begging the question of how an oxidation-reduction flavoprotein affects developmental and cellular signaling processes.

  19. Protein degradation and iron homeostasis.

    Science.gov (United States)

    Thompson, Joel W; Bruick, Richard K

    2012-09-01

    Regulation of both systemic and cellular iron homeostasis requires the capacity to sense iron levels and appropriately modify the expression of iron metabolism genes. These responses are coordinated through the efforts of several key regulatory factors including F-box and Leucine-rich Repeat Protein 5 (FBXL5), Iron Regulatory Proteins (IRPs), Hypoxia Inducible Factor (HIF), and ferroportin. Notably, the stability of each of these proteins is regulated in response to iron. Recent discoveries have greatly advanced our understanding of the molecular mechanisms governing iron-sensing and protein degradation within these pathways. It has become clear that iron's privileged roles in both enzyme catalysis and protein structure contribute to its regulation of protein stability. Moreover, these multiple pathways intersect with one another in larger regulatory networks to maintain iron homeostasis. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22349011

  20. Bone Metabolism in Anorexia Nervosa

    OpenAIRE

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in ...

  1. Sleeping, Waking, ... and Glucose Homeostasis

    OpenAIRE

    Rudic R. Daniel; McNamara Peter; Curtis Anne-Maria; Boston Raymond C; Panda Satchidananda; Hogenesch John B; FitzGerald Garret A

    2004-01-01

    Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and is depressed in Clock mutants, but the counte...

  2. Zinc bioavailability and homeostasis1234

    OpenAIRE

    Hambidge, K Michael; Miller, Leland V; Westcott, Jamie E; Sheng, Xiaoyang; Krebs, Nancy F.

    2010-01-01

    Zinc has earned recognition recently as a micronutrient of outstanding and diverse biological, clinical, and global public health importance. Regulation of absorption by zinc transporters in the enterocyte, together with saturation kinetics of the absorption process into and across the enterocyte, are the principal means by which whole-body zinc homeostasis is maintained. Several physiologic factors, most notably the quantity of zinc ingested, determine the quantity of zinc absorbed and the e...

  3. Bone Metabolism in Adolescents with Anorexia Nervosa

    OpenAIRE

    Misra, Madhusmita; Klibanski, Anne

    2011-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often ...

  4. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation.

    Science.gov (United States)

    Jansen, Jos C; Cirak, Sebahattin; van Scherpenzeel, Monique; Timal, Sharita; Reunert, Janine; Rust, Stephan; Pérez, Belén; Vicogne, Dorothée; Krawitz, Peter; Wada, Yoshinao; Ashikov, Angel; Pérez-Cerdá, Celia; Medrano, Celia; Arnoldy, Andrea; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; Quelhas, Dulce; Diogo, Luisa; Rymen, Daisy; Jaeken, Jaak; Guffon, Nathalie; Cheillan, David; van den Heuvel, Lambertus P; Maeda, Yusuke; Kaiser, Olaf; Schara, Ulrike; Gerner, Patrick; van den Boogert, Marjolein A W; Holleboom, Adriaan G; Nassogne, Marie-Cécile; Sokal, Etienne; Salomon, Jody; van den Bogaart, Geert; Drenth, Joost P H; Huynen, Martijn A; Veltman, Joris A; Wevers, Ron A; Morava, Eva; Matthijs, Gert; Foulquier, François; Marquardt, Thorsten; Lefeber, Dirk J

    2016-02-01

    Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal

  5. Role of FGF/FGFR signaling in skeletal development and homeostasis:learning from mouse models

    Institute of Scientific and Technical Information of China (English)

    Nan Su; Min Jin; Lin Chen

    2014-01-01

    Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis.

  6. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina;

    2004-01-01

    Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone form...

  7. The response of bone to unloading

    Science.gov (United States)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  8. Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency

    DEFF Research Database (Denmark)

    Haaber, Anne Birgitte; Rosenfalck, A M; Hansen, B;

    2000-01-01

    Calcium and vitamin D homeostasis seem to be abnormal in patients with exocrine pancreatic dysfunction resulting from cystic fibrosis. Only a few studies have evaluated and described bone mineral metabolism in patients with chronic pancreatitis and pancreatic insufficiency....

  9. Bone Grafts

    Science.gov (United States)

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

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

    OpenAIRE

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

    2013-01-01

    Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and f...

  11. Ascorbate Synthesis Pathway: DUAL ROLE OF ASCORBATE IN BONE HOMEOSTASIS*

    OpenAIRE

    Gabbay, Kenneth H.; Bohren, Kurt M.; Morello, Roy; Bertin, Terry; Liu, Jeff; Vogel, Peter

    2010-01-01

    Using mouse gene knock-out models, we identify aldehyde reductase (EC 1.1.1.2, Akr1a4 (GR)) and aldose reductase (EC 1.1.1.21, Akr1b3 (AR)) as the enzymes responsible for conversion of d-glucuronate to l-gulonate, a key step in the ascorbate (ASC) synthesis pathway in mice. The gene knock-out (KO) mice show that the two enzymes, GR and AR, provide ∼85 and ∼15% of l-gulonate, respectively. GRKO/ARKO double knock-out mice are unable to synthesize ASC (>95% ASC deficit) and develop scurvy. The G...

  12. Mechanical Loading Synergistically Increases Trabecular Bone Volume and Improves Mechanical Properties in the Mouse when BMP Signaling Is Specifically Ablated in Osteoblasts.

    Directory of Open Access Journals (Sweden)

    Ayaka Iura

    Full Text Available Bone homeostasis is affected by several factors, particularly mechanical loading and growth factor signaling pathways. There is overwhelming evidence to validate the importance of these signaling pathways, however, whether these signals work synergistically or independently to contribute to proper bone maintenance is poorly understood. Weight-bearing exercise increases mechanical load on the skeletal system and can improves bone quality. We previously reported that conditional knockout (cKO of Bmpr1a, which encodes one of the type 1 receptors for Bone Morphogenetic Proteins (BMPs, in an osteoblast-specific manner increased trabecular bone mass by suppressing osteoclastogenesis. The cKO bones also showed increased cortical porosity, which is expected to impair bone mechanical properties. Here, we evaluated the impact of weight-bearing exercise on the cKO bone phenotype to understand interactions between mechanical loading and BMP signaling through BMPR1A. Male mice with disruption of Bmpr1a induced at 9 weeks of age, exercised 5 days per week on a motor-driven treadmill from 11 to 16 weeks of age. Trabecular bone volume in cKO tibia was further increased by exercise, whereas exercise did not affect the trabecular bone in the control genotype group. This finding was supported by decreased levels of osteoclasts in the cKO tibiae. The cortical porosity in the cKO bones showed a marginally significant decrease with exercise and approached normal levels. Exercise increased ductility and toughness in the cKO bones. Taken together, reduction in BMPR1A signaling may sensitize osteoblasts for mechanical loading to improve bone mechanical properties.

  13. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    OpenAIRE

    2015-01-01

    Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, suc...

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

    Science.gov (United States)

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

    2010-08-01

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

  15. Alpha Klotho and phosphate homeostasis

    OpenAIRE

    Bian, Ao; Xing, Changying; Hu, Ming Chang

    2014-01-01

    The Klotho family consists of three single-pass transmembrane proteins—αKlotho, βKlotho and γKlotho. Each of them combines with fibroblast growth factor (FGF) receptors (FGFRs) to form receptor complexes for various FGF’s. αKlotho is a co-receptor for physiological FGF23 signaling and appears essential for FGF23-mediated regulation of mineral metabolism. αKlotho protein also plays a FGF23-independent role in phosphate homeostasis. Animal experimental studies and clinical observations have dem...

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

    Science.gov (United States)

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

    2013-10-01

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

  17. Mechanically loaded myotubes affect osteoclast formation.

    Science.gov (United States)

    Juffer, Petra; Jaspers, Richard T; Klein-Nulend, Jenneke; Bakker, Astrid D

    2014-03-01

    In response to mechanical loading skeletal muscle produces numerous growth factors and cytokines that enter the circulation. We hypothesized that myotubes produce soluble factors that affect osteoclast formation and aimed to identify which osteoclastogenesis-modulating factors are differentially produced by mechanically stimulated myotubes. C2C12 myotubes were subjected to mechanical loading by cyclic strain for 1 h, and postincubated with or without cyclic strain for 24 h. The effect of cyclic strain on gene expression in myotubes was determined by PCR. Conditioned medium (CM) was collected from cultures of unloaded and loaded myotubes and from MLO-Y4 osteocytes. CM was added to mouse bone marrow cells containing osteoclast precursors, and after 6 days osteoclasts were counted. Compared to unconditioned medium, CM from unloaded osteocytes increased osteoclast formation, while CM from unloaded myotubes decreased osteoclast formation. Cyclic strain strongly enhanced IL-6 expression in myotubes. CM from cyclically strained myotubes increased osteoclast formation compared to CM from unloaded myotubes, but this effect did not occur in the presence of an IL-6 antibody. In conclusion, mechanically loaded myotubes secrete soluble factors, among others IL-6, which affect osteoclast formation. These results suggest that muscle could potentially affect bone homeostasis in vivo via production of growth factors and/or cytokines. PMID:24264813

  18. The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study.

    Science.gov (United States)

    Armstrong, Linlea; Jett, Kimberly; Birch, Patricia; Kendler, David L; McKay, Heather; Tsang, Erica; Stevenson, David A; Hanley, David A; Egeli, Deetria; Burrows, Melonie; Friedman, J M

    2013-07-01

    People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling-matched case-control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X-ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT-derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25-OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1. PMID:23713011

  19. Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers

    International Nuclear Information System (INIS)

    Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect

  20. Bone metabolism during pregnancy.

    Science.gov (United States)

    Salles, Jean Pierre

    2016-06-01

    During pregnancy, mineral concentrations, of calcium and phosphorus in particular, are maintained at a high level in fetal blood so that the developing skeleton may accrete adequate mineral content. The placenta actively transports minerals for this purpose. Maternal intestinal absorption increases in order to meet the fetal demand for calcium, which is only partly dependent on calcitriol. Mineral regulation is essentially dependent on parathyroid hormone (PTH) and PTH-related protein (PTHrP). The calcium-sensing receptor (CaSR) regulates PTH and PTHrP production. If calcium intake is insufficient, the maternal skeleton will undergo resorption due to PTHrP. After birth, a switch from fetal to neonatal homeostasis occurs through increase in PTH and calcitriol, and developmental adaptation of the kidneys and intestines with bone turnover contributing additional mineral to the circulation. Calcium absorption becomes progressively active and dependent on calcitriol. The postnatal skeleton can transiently present with osteoposis but adequate mineral diet usually allows full restoration. Cases of primary osteoporosis must be identified. Loss of trabecular mineral content occurs during lactation in order to provide calcium to the newborn. This programmed bone loss is dependent on a "brain-breast-bone" circuit. The physiological bone resorption during reproduction does not normally cause fractures or persistent osteoporosis. Women who experience fracture are likely to have other causes of bone loss. PMID:27157104

  1. Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis.

    Science.gov (United States)

    Sharma, Ashish R; Jagga, Supriya; Lee, Sang-Soo; Nam, Ju-Suk

    2013-01-01

    Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients. PMID:24084727

  2. Interplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Ju-Suk Nam

    2013-09-01

    Full Text Available Osteoarthritis (OA is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients.

  3. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: A randomized, double-blind, placebo controlled study

    NARCIS (Netherlands)

    Brink, E.; Coxam, V.; Robins, S.; Wahala, K.; Cassidy, A.; Branca, F.

    2008-01-01

    Background: Osteoporosis is a major health problem. It was hypothesized that isoflavone-containing products may be a potential alternative to hormone replacement therapy for preventing bone loss during the menopausal transition. Objective: The objective was to investigate whether the consumption of

  4. Bone Targeted Therapies for Bone Metastasis in Breast Cancer

    OpenAIRE

    Wajeeha Razaq

    2013-01-01

    Cancer metastasis to the bone develops commonly in patients with various malignancies, and is a major cause of morbidity and diminished quality of life in many affected patients. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to the bone metastasis. The tendency of cancer cells to metastasize to bone is probably the end result of many factors including vascular pathways, the highly ...

  5. Dietary fructose and glucose differentially affect lipid and glucose homeostasis

    Science.gov (United States)

    Absorbed glucose and fructose differ in that glucose largely escapes first pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these two monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial trig...

  6. Epigenetic Regulation of Cholesterol Homeostasis

    Directory of Open Access Journals (Sweden)

    Steve eMeaney

    2014-09-01

    Full Text Available Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g. the Hedgehog system. A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more ‘traditional’ regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review.

  7. A non-synonymous coding change in the CYP19A1 gene Arg264Cys (rs700519 does not affect circulating estradiol, bone structure or fracture

    Directory of Open Access Journals (Sweden)

    Wang Jenny Z

    2011-12-01

    Full Text Available Abstract Background The biosynthesis of estrogens from androgens is catalyzed by aromatase P450 enzyme, coded by the CYP19A1 gene on chromosome 15q21.2. Genetic variation within the CYP19A1 gene sequence has been shown to alter the function of the enzyme. The aim of this study is to investigate whether a non-synonymous Arg264Cys (rs700519 single nucleotide polymorphism (SNP is associated with altered levels of circulating estradiol, areal bone mineral density or fracture. Methods This population- based study of 1,022 elderly Caucasian women (mean age 74.95 ± 2.60 years was genotyped for the rs700519 SNP were analyzed to detect any association with endocrine and bone phenotypes. Results The genotype frequencies were 997 wildtype (97.6%, 24 heterozygous (2.3% and 1 homozygous (0.1%. When individuals were grouped by genotype, there was no association between the polymorphism and serum estradiol (wildtype 27.5 ± 16.0; variants 31.2 ± 18.4, P = 0.27. There was also no association seen on hip bone mineral density (wildtype 0.81 ± 0.12; 0.84 ± 0.14 for variants, P = 0.48 or femoral neck bone mineral density (0.69 ± 0.10 for wildtype; 0.70 ± 0.12 for variants, P = 0.54 before or after correction of the data with age, height, weight and calcium therapy. There were also no associations with quantitative ultrasound measures of bone structure (broadband ultrasound attenuation, speed of sound and average stiffness. Conclusions In a cohort of 1,022 elderly Western Australian women, the presence of Arg264Cys (rs700519 polymorphism was not found to be associated with serum estradiol, bone structure or phenotypes.

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

    Science.gov (United States)

    Funck-Brentano, Thomas; Cohen-Solal, Martine

    2011-04-01

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

  9. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  10. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  11. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  12. Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bendtzen, Klaus; Beck-Nielsen, H

    1997-01-01

    flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no...

  13. Sire carcass breeding values affect body composition in lambs--2. Effects on fat and bone weight and their distribution within the carcass as measured by computed tomography.

    Science.gov (United States)

    Anderson, F; Williams, A; Pannier, L; Pethick, D W; Gardner, G E

    2016-06-01

    This study assessed the effect of paternal Australian Sheep Breeding Values for post weaning c-site eye muscle depth (PEMD) and fat depth (PFAT), and post weaning weight (PWWT) on the composition of lamb carcasses. Composition was measured using computed tomography scans of 1665 lambs which were progeny of 85 Maternal, 115 Merino and 155 Terminal sires. Reducing sire PFAT decreased carcass fat weight by 4.8% and increased carcass bone by 1.3% per unit of PFAT (range 5.1 mm). Increasing sire PEMD reduced carcass fat weight by 3.8% in Maternal and 2% in Terminal sired lambs per unit of PEMD (range 4.3 and 7.8 mm), with no impact on bone. Increasing sire PWWT reduced carcass fat weight, but only at some experimental locations. Differences in composition varied between sire types with Maternal sired lambs having the most fat and Merino sired lambs the greatest bone weight. Genetic effects on fatness were greater than the environmental or production factor effects, with the converse true of bone. PMID:26914513

  14. Short-term immunosuppressive therapy does not affect the density of the pre-existing bone around titanium implants placed in rabbits

    Directory of Open Access Journals (Sweden)

    Duarte Poliana Mendes

    2003-01-01

    Full Text Available The aim of this study was to evaluate the influence of the administration and withdrawal of cyclosporin A/nifedipine on the bone density in a lateral area adjacent to implants placed in rabbits. Two screw-type titanium implants were placed bilaterally in twenty-eight New Zealand rabbits. The animals were assigned to one of the following groups and received daily subcutaneous injections for 14 days: Groups A and C: vehicle (dimethyl sulfoxide; Groups B and D: CsA (10 mg/kg plus nifedipine (50 mg/kg. The animals in Groups A and B were sacrificed 14 days postoperatively and, in Groups C and D, 42 days postoperatively. After sacrifice, the tibiae were removed and undecalcified sections were obtained. Bone density was obtained in a 500 mm-wide zone lateral to the implant surface. Intergroup analysis showed no significant difference (p > 0.05 in the degree of bone density between control and test groups either on day 14 or on day 42. Thus, it appears that a short-term immunosuppressive therapy may not present a negative influence on the density of the pre-existing bone around titanium implants placed in rabbits.

  15. Relationship between nanoscale mineral properties and calcein labeling in mineralizing bone surfaces

    OpenAIRE

    Aido, Marta; Kerschnitzki, Michael; Hoerth, Rebecca; Burghammer, Manfred; Montero, Cédric; Checa, Sara; Fratzl, Peter; Duda, Georg; Willie, Bettina; Wagermaier, Wolfgang

    2014-01-01

    Bone's mineral properties, such as particle thickness and degree of alignment have been associated with bone quality. Bone formation, remodeling, aging of the tissue and mineral homeostasis influence mineral particle properties leading to specific patterns across bone. Scanning small angle X-ray scattering (sSAXS) with synchrotron radiation is a powerful tool, which allows us to study bone's nanoscale mineral properties in a position-resolved way. We used sSAXS, fluorescence light microscopy ...

  16. Osteobiology: newest bone organ topics and the platelet-rich plasma treatment.

    OpenAIRE

    Ananias García Cardona; Gérgory Alfonso García; Ómar Ramón Mejía; Mario Vittorino Mejía; Dianney Clavijo Grimaldi; Ciro Alfonso Casadiego Torrado

    2007-01-01

    The bone is a dynamic tissue taht provides mechanical support, physical protection, storage site for minerals, and enables genesis movement. The bone biology (osteobiology) is regulated by the balance betqeen osteoblastic formation and osteoclatic resorption. the skeletal bone homeostasis is influenced by components of the bone marrow organ, neuroendocrine system and hemato-inmmune system. The purpose of this review is to describe the biodynamic of the bone organ, and actual terapeutics with ...

  17. Probabilistic Perception, Empathy, and Dynamic Homeostasis: Insights in Autism Spectrum Disorders and Conduct Disorders

    OpenAIRE

    Guilé, Jean Marc

    2014-01-01

    Homeostasis is not a permanent and stable state but instead results from conflicting forces. Therefore, infants have to engage in dynamic exchanges with their environment, in biological, cognitive, and affective domains. Empathy is an adaptive response to these environmental challenges, which contributes to reaching proper dynamic homeostasis and development. Empathy relies on implicit interactive processes, namely probabilistic perception and synchrony, which will be reviewed in the article....

  18. Transport, signaling, and homeostasis of potassium and sodium in plants

    Institute of Scientific and Technical Information of China (English)

    Eri Adams; Ryoung Shin

    2014-01-01

    Potassium (Kþ) is an essential macronutrient in plants and a lack of Kþ significantly reduces the potential for plant growth and development. By contrast, sodium (Naþ), while beneficial to some extent, at high concentrations it disturbs and inhibits various physiological processes and plant growth. Due to their chemical similarities, some functions of Kþ can be undertaken by Naþ but Kþ homeostasis is severely affected by salt stress, on the other hand. Recent advances have highlighted the fascinating regulatory mechanisms of Kþ and Naþ transport and signaling in plants. This review summarizes three major topics:(i) the transport mechanisms of Kþ and Naþ from the soil to the shoot and to the cellular compartments; (i ) the mechanisms through which plants sense and respond to Kþ and Naþ availability; and (i i) the components involved in maintenance of Kþ/Naþ homeostasis in plants under salt stress.

  19. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    Science.gov (United States)

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-01-01

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis. PMID:25864946

  20. Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women: results of a two-year placebo-controlled trial.

    Science.gov (United States)

    Engelke, Klaus; Fuerst, Thomas; Dardzinski, Bernard; Kornak, John; Ather, Shabana; Genant, Harry K; de Papp, Anne

    2015-01-01

    Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral density (aBMD) at the spine and hip of postmenopausal women. To gain additional insight into the effects on trabecular and cortical bone, we analyzed quantitative computed tomography (QCT) data of postmenopausal women treated with odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical Physics, University of Erlangen, Erlangen, Germany). This international, randomized, double-blind, placebo-controlled, 2-year, phase 3 trial enrolled 214 postmenopausal women (mean age 64 years) with low aBMD. Subjects were randomized to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received calcium and vitamin D. Hip QCT scans at 24 months were available for 158 women (ODN: n = 78 women; PBO: n = 80 women). There were consistent and significant differential treatment effects (ODN-PBO) for total hip integral (5.4%), trabecular volumetric BMD (vBMD) (12.2%), and cortical vBMD (2.5%) at 24 months. There was no significant differential treatment effect on integral bone volume. Results for bone mineral content (BMC) closely matched those for vBMD for integral and trabecular compartments. However, with small but mostly significant differential increases in cortical volume (1.0% to 1.3%) and thickness (1.4% to 1.9%), the percentage cortical BMC increases were numerically larger than those of vBMD. With a total hip BMC differential treatment effect (ODN-PBO) of nearly 1000 mg, the proportions of BMC attributed to cortical gain were 45%, 44%, 52%, and 40% for the total, neck, trochanter, and intertrochanter subregions, respectively. In postmenopausal women treated for 2 years, odanacatib improved integral, trabecular, and cortical vBMD and BMC at all femur regions relative to placebo when assessed by MIAF. Cortical volume and thickness increased significantly in all regions except the femoral neck. The increase in cortical volume and BMC paralleled the increase in

  1. Pancreatic regulation of glucose homeostasis.

    Science.gov (United States)

    Röder, Pia V; Wu, Bingbing; Liu, Yixian; Han, Weiping

    2016-01-01

    In order to ensure normal body function, the human body is dependent on a tight control of its blood glucose levels. This is accomplished by a highly sophisticated network of various hormones and neuropeptides released mainly from the brain, pancreas, liver, intestine as well as adipose and muscle tissue. Within this network, the pancreas represents a key player by secreting the blood sugar-lowering hormone insulin and its opponent glucagon. However, disturbances in the interplay of the hormones and peptides involved may lead to metabolic disorders such as type 2 diabetes mellitus (T2DM) whose prevalence, comorbidities and medical costs take on a dramatic scale. Therefore, it is of utmost importance to uncover and understand the mechanisms underlying the various interactions to improve existing anti-diabetic therapies and drugs on the one hand and to develop new therapeutic approaches on the other. This review summarizes the interplay of the pancreas with various other organs and tissues that maintain glucose homeostasis. Furthermore, anti-diabetic drugs and their impact on signaling pathways underlying the network will be discussed. PMID:26964835

  2. Porous surface modified bioactive bone cement for enhanced bone bonding.

    Directory of Open Access Journals (Sweden)

    Qiang He

    Full Text Available BACKGROUND: Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth. MATERIALS AND METHODS: The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant-bone interface was also investigated by push-out tests. RESULTS: The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony

  3. Soy isoflavones do not affect bone resorption in postmenopausal women: A dose-response study using a novel approach with Ca-41

    OpenAIRE

    Cheong, J. M. K.; Martin, B R; Jackson, G.S.; Elmore, D.; McCabe, G. P.; Nolan, J R; Barnes, S.; Peacock, M.; Weaver, C. M.

    2007-01-01

    Introduction: The purpose of this 3-way crossover study was to identify the effective dose of soy protein isolate enriched with isoflavones for suppressing bone resorption in postmenopausal women using a novel, rapid assessment of antibone resorbing treatments. Methods: Thirteen postmenopausal women (>= 6 yr since menopause) were predosed with Ca-41 iv. After a 200-d baseline period, subjects were given 43 g soy p...

  4. Roles of hyaluronan in bone resorption

    Directory of Open Access Journals (Sweden)

    Prince Charles W

    2004-04-01

    Full Text Available Abstract Background Hyaluronan, an unsulfated glycosaminoglycan, while being closely linked to osteoclast function several years ago, has received little attention lately. Given recent new knowledge of hyaluronan's possible cell binding abilities, it is important to re-examine the role of this polysaccharide in bone homeostasis. Discussion Previously published data demonstrating a linkage between induction of hyaluronan synthesis and osteoclast-mediated bone resorption are reviewed. Suggestions are made involving the cell binding ability of hyaluronan and its potential to mediate osteoclast binding to bone surfaces and its potential to serve as a diffusion barrier and participate in the sealing zone required for osteoclast-mediated bone resorption. Summary This brief article summarizes previous studies linking HA to bone resorption and suggests roles for hyaluronan in the process of bone resorption.

  5. Updates in biological therapies for knee injuries: bone

    OpenAIRE

    Kfuri, Mauricio; de Freitas, Rafael Lara; Batista, Bruno Bellaguarda; Salim, Rodrigo; Castiglia, Marcello Teixeira; Tavares, Ricardo Antonio; Araújo, Paulo Henrique

    2014-01-01

    Bone is a unique tissue because of its mechanical properties, ability for self-repair, and enrollment in different metabolic processes such as calcium homeostasis and hematopoietic cell production. Bone barely tolerates deformation and tends to fail when overloaded. Fracture healing is a complex process that in particular cases is impaired. Osteoprogenitor cells proliferation, growth factors, and a sound tridimensional scaffold at fracture site are key elements for new bone formation and depo...

  6. Androgens and Bone

    OpenAIRE

    Clarke, Bart L.; Khosla, Sundeep

    2008-01-01

    Testosterone is the major gonadal sex steroid produced by the testes in men. Testosterone is also produced in smaller amounts by the ovaries in women. The adrenal glands produce the weaker androgens dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. These androgens collectively affect skeletal homeostasis throughout life in both men and women, particularly at puberty and during adult life. Because testosterone can be metabolized to estradiol by the aromatase enzyme, ...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  8. FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player?

    OpenAIRE

    RAZZAQUE, M. Shawkat

    2008-01-01

    Understanding the physiological regulation of mineral ion metabolism is essential for determining the pathomechanisms of skeletal, vascular, and renal diseases associated with an abnormal regulation of calcium and phosphate homeostasis. Normal calcium and phosphate balance is delicately maintained by endocrine factors that coordinate to influence the functions of the intestine, bone, parathyroid gland, and kidney. Under physiological conditions, the kidneys play an important role in maintaini...

  9. Impaired osteoclast homeostasis in the cystatin B-deficient mouse model of progressive myoclonus epilepsy

    Directory of Open Access Journals (Sweden)

    Otto Manninen

    2015-12-01

    Full Text Available Progressive myoclonus epilepsy of Unverricht–Lundborg type (EPM1 is an autosomal recessively inherited disorder characterized by incapacitating stimulus-sensitive myoclonus and tonic-clonic epileptic seizures with onset at the age of 6 to 16 years. EPM1 patients also exhibit a range of skeletal changes, e.g., thickened frontal cranial bone, arachnodactyly and scoliosis. Mutations in the gene encoding cystatin B (CSTB underlie EPM1. CSTB is an inhibitor of cysteine cathepsins, including cathepsin K, a key enzyme in bone resorption by osteoclasts. CSTB has previously been shown to protect osteoclasts from experimentally induced apoptosis and to modulate bone resorption in vitro. Nevertheless, its physiological function in bone and the cause of the bone changes in patients remain unknown. Here we used the CSTB-deficient mouse (Cstb−/− model of EPM1 to evaluate the contribution of defective CSTB protein function on bone pathology and osteoclast differentiation and function. Micro-computed tomography of hind limbs revealed thicker trabeculae and elevated bone mineral density in the trabecular bone of Cstb−/− mice. Histology from Cstb−/− mouse bones showed lower osteoclast count and thinner growth plates in long bones. Bone marrow-derived osteoclast cultures revealed lower osteoclast number and size in the Cstb−/− group. Cstb−/− osteoclasts formed less and smaller resorption pits in an in vitro assay. This impaired resorptive capacity was likely due to a decrease in osteoclast numbers and size. These data imply that the skeletal changes in Cstb−/− mice and in EPM1 patients are a result of CSTB deficiency leading to impaired osteoclast formation and consequently compromised resorptive capacity. These results suggest that the role of CSTB in osteoclast homeostasis and modulation of bone metabolism extends beyond cathepsin K regulation.

  10. Tarsal bone disintegration in leprosy

    International Nuclear Information System (INIS)

    Tarsal bone disintegration is characterised by fragmentation and progressive collapse of one or more tarsal bones. It occurs in 10% of leprosy patients, and is responsible for many severe foot deformities associated with this disease. The main cause is micro-traumata, but sensory impairment, sepsis and osteoporosis are predisposing factors. In this series of 400 consecutive patients the talus and navicular were involved most frequently (72% of 119 tarsal lesions). Treatment, including prolonged immobilisation of the foot, results in dense sclerosis of the affected bone, and leaves a functional limb. Initial radiological features include bone fragmentation, calcified fragments in adjacent soft tissues, linear fractures, progressive compression and deformity of the affected bone, loss of density of the affected bone and flattening of the longitudinal plantar arch. Illustrative case histories are presented, and the differential diagnosis discussed. (author)

  11. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  12. Biochemical markers of bone turnover

    International Nuclear Information System (INIS)

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

  13. The role of malate in plant homeostasis

    OpenAIRE

    Finkemeier, Iris; Sweetlove, Lee J.

    2009-01-01

    Malate is a central metabolite of the plant cell with important roles in plant physiology and metabolism. Here, we summarize the most recent advances in our understanding of malate homeostasis in central metabolism, guard cell functioning, and root exudation.

  14. The role of sirtuins in cellular homeostasis.

    Science.gov (United States)

    Kupis, Wioleta; Pałyga, Jan; Tomal, Ewa; Niewiadomska, Ewa

    2016-09-01

    Sirtuins are evolutionarily conserved nicotinamide adenine dinucleotide (NAD(+))-dependent lysine deacylases or ADP-ribosyltransferases. These cellular enzymes are metabolic sensors sensitive to NAD(+) levels that maintain physiological homeostasis in the animal and plant cells. PMID:27154583

  15. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd;

    2010-01-01

    expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  16. Bone mineral density and markers of bone turnover in patients with renal transplantation and regular hemodialysis

    OpenAIRE

    Samir M. Ibrahim,. Khalid H Abdel-Mageed, Magdi M El-Sharkawy

    2002-01-01

    Background: Decreased bone mineral density (BMD) is a known complication for the uremic state antedating dialysis / renal transplantation (RTx). The issue of stabilized versus continued decrease of BMD especially on long-term basis, continues to be unresolved. Patients and Methods: !"#"hemodialysis (HD-#" $% " &'( )&'(-group) had been evaluated for metabolic bone changes by calcium homeostasis parameters (serum calcium, phosphorus, alkaline phosphatase "ALP" and vitamin D "calcitriol"), marke...

  17. High-fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis through Alteration of the Bone Marrow Environment

    OpenAIRE

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael; Puzas, J. Edward; Boyce, F. Brendan; Mooney, A. Robert; Xing, Lianping

    2015-01-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks...

  18. Iron Homeostasis and Nutritional Iron Deficiency123

    OpenAIRE

    Theil, Elizabeth C.

    2011-01-01

    Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins enc...

  19. Leptin therapy, insulin sensitivity, and glucose homeostasis

    OpenAIRE

    Gilberto Paz-Filho; Claudio Mastronardi; Ma-Li Wong; Julio Licinio

    2012-01-01

    Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insu...

  20. Iron Homeostasis and the Inflammatory Response

    OpenAIRE

    Wessling-Resnick, Marianne

    2010-01-01

    Iron and its homeostasis are intimately tied to the inflammatory response. The adaptation to iron deficiency, which confers resistance to infection and improves the inflammatory condition, underlies what is probably the most obvious link: the anemia of inflammation or chronic disease. A large number of stimulatory inputs must be integrated to tightly control iron homeostasis during the inflammatory response. In order to understand the pathways of iron trafficking and how they are regulated, t...

  1. A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, H; Jensen, Ole N; Moiseeva, Elena P;

    2003-01-01

    , which induced hBMS cell proliferation by 3-fold. This effect was abolished by IGF-I. PC3 CM and galectin-1 in concentrations of 10 and 1000 ng/ml increased the alkaline phosphatase (ALP) activity of hBMS cells up to 175 +/- 27%, 137 +/- 8%, and 131 +/- 11%, respectively, compared with ALP activity of......Prostate cancer cells metastasize to bone causing a predominantly osteosclerotic response. It has been shown that cells from the human prostate cancer cell line PC3 secrete factors that influence the behavior of osteoblast-like cells. Some of these factors with mitogenic activity have been found to...

  2. Macrophages: Their Emerging Roles in Bone.

    Science.gov (United States)

    Sinder, Benjamin P; Pettit, Allison R; McCauley, Laurie K

    2015-12-01

    Macrophages are present in nearly all tissues and are critical for development, homeostasis, and regeneration. Resident tissue macrophages of bone, termed osteal macrophages, are recently classified myeloid cells that are distinct from osteoclasts. Osteal macrophages are located immediately adjacent to osteoblasts, regulate bone formation, and play diverse roles in skeletal homeostasis. Genetic or pharmacological modulation of macrophages in vivo results in significant bone phenotypes, and these phenotypes depend on which macrophage subsets are altered. Macrophages are also key mediators of osseous wound healing and fracture repair, with distinct roles at various stages of the repair process. A central function of macrophages is their phagocytic ability. Each day, billions of cells die in the body and efferocytosis (phagocytosis of apoptotic cells) is a critical process in both clearing dead cells and recruitment of replacement progenitor cells to maintain homeostasis. Recent data suggest a role for efferocytosis in bone biology and these new mechanisms are outlined. Finally, although macrophages have an established role in primary tumors, emerging evidence suggests that macrophages in bone support cancers which preferentially metastasize to the skeleton. Collectively, this developing area of osteoimmunology raises new questions and promises to provide novel insights into pathophysiologic conditions as well as therapeutic and regenerative approaches vital for skeletal health. PMID:26531055

  3. Low Bone Density

    Science.gov (United States)

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

  4. Sodium butyrate improved cognitive and affective disorder of PD model mice mainly via maintenance of histone acetylation homeostasis%丁酸钠通过维持乙酰化平衡改善帕金森病模型鼠认知功能和情感障碍

    Institute of Scientific and Technical Information of China (English)

    宋玫香; 张岩; 王芳; 王虹; 包金风

    2012-01-01

    . Conclusion MPTP decreased the expression of TH, and induced cognitive and affective disorder, which may interfere with the homeostasis of histone acetylation; sodium butyrate could increase TH protein expression and improve cognitive and affective disorder of PD model mice. The mechanism may be through protecting dopamine neurons and maintaining the ho -meostasis of histone acetylation and deacetylation .

  5. SGLT2 inhibitor therapy improves blood glucose but does not prevent diabetic bone disease in diabetic DBA/2J male mice.

    Science.gov (United States)

    Thrailkill, Kathryn M; Clay Bunn, R; Nyman, Jeffry S; Rettiganti, Mallikarjuna R; Cockrell, Gael E; Wahl, Elizabeth C; Uppuganti, Sasidhar; Lumpkin, Charles K; Fowlkes, John L

    2016-01-01

    Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by μCT analysis and a three-point bending test of the femur, and vertebral bone strength was determined by compression testing. In the femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical bone area, cortical thickness and minimal moment of inertia occurred in DM (p<0.0001, for all) while cortical porosity was increased (p<0.0001). These DM changes were associated with reduced fracture resistance (decreased material strength and toughness; decreased structural strength and rigidity; p<0.001 for all). Significant increases in PTH (p<0.0001), RatLAPs (p=0.0002), and urine calcium concentration (p<0.0001) were also seen in DM. Canagliflozin treatment improved BG in DM mice by ~35%, but did not improve microarchitectural parameters. Instead, in canagliflozin-treated diabetic mice, a further increase in RatLAPs was evident, possibly suggesting a drug-related intensification of bone resorption. Additionally, detrimental metaphyseal changes were noted in canagliflozin-treated control mice. Hence, diabetic bone disease was not favorably affected by canagliflozin treatment, perhaps due to insufficient glycemic improvement. Instead, in control mice, long-term exposure to SGLT2 inhibition was associated with

  6. Heterogeneous Glycation of Cancellous Bone and Its Association with Bone Quality and Fragility

    OpenAIRE

    Karim, Lamya; Vashishth, Deepak

    2012-01-01

    Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors ...

  7. Mechanical homeostasis regulating adipose tissue volume

    Directory of Open Access Journals (Sweden)

    Svedman Paul

    2007-09-01

    Full Text Available Abstract Background The total body adipose tissue volume is regulated by hormonal, nutritional, paracrine, neuronal and genetic control signals, as well as components of cell-cell or cell-matrix interactions. There are no known locally acting homeostatic mechanisms by which growing adipose tissue might adapt its volume. Presentation of the hypothesis Mechanosensitivity has been demonstrated by mesenchymal cells in tissue culture. Adipocyte differentiation has been shown to be inhibited by stretching in vitro, and a pathway for the response has been elucidated. In humans, intermittent stretching of skin for reconstructional purposes leads to thinning of adipose tissue and thickening of epidermis – findings matching those observed in vitro in response to mechanical stimuli. Furthermore, protracted suspension of one leg increases the intermuscular adipose tissue volume of the limb. These findings may indicate a local homeostatic adipose tissue volume-regulating mechanism based on movement-induced reduction of adipocyte differentiation. This function might, during evolution, have been of importance in confined spaces, where overgrowth of adipose tissue could lead to functional disturbance, as for instance in the turtle. In humans, adipose tissue near muscle might in particular be affected, for instance intermuscularly, extraperitoneally and epicardially. Mechanical homeostasis might also contribute to protracted maintainment of soft tissue shape in the face and neck region. Testing of the hypothesis Assessment of messenger RNA-expression of human adipocytes following activity in adjacent muscle is planned, and study of biochemical and volumetric adipose tissue changes in man are proposed. Implications of the hypothesis The interpretation of metabolic disturbances by means of adipose tissue might be influenced. Possible applications in the head and neck were discussed.

  8. Anabolic Vitamin D Analogs as Countermeasures to Bone Loss

    Science.gov (United States)

    Li, Wei; Duncan, Randall L.; Karin, Norman J.; Farach-Carson, Mary C.

    1997-01-01

    We demonstrated for the first time that vitamin D3 influences the effect of PTH on bone cell calcium ion levels. This is a rapid effect, taking place within seconds/minutes. This may prove to be a critical contribution to our understanding of bone physiology in that these two hormones are among the most potent regulators of bone calcium content and of systemic calcium homeostasis. Together with the data gathered from the study of astronauts exposed to microgravity for extended periods, these observations suggest the interaction of vitamin D3 and PTH as a possible therapeutic target in the treatment of bone loss disorders such as osteoporosis and disuse atrophy. Chronic exposure of cultured osteoblasts to vitamin D, altered the number of voltage-sensitive Ca(+2) channels expressed. Estrogen treatment yielded a similar result, suggesting that there is overlap in the mechanism by which these hormones elicit long-term effects on bone cell calcium homeostasis.

  9. Bone scanning in osteoporosis

    International Nuclear Information System (INIS)

    This paper reports on bone scanning in osteoporosis a diagnosis of osteoporosis most often follows fracture, and clearly this should be confirmed by x-ray. The bone scan therefore does not have an important role to play in the initial diagnosis of osteoporosis. While the exact mechanism by which the 99mTc-labeled diphosphonates localize in the skeleton is not fully understood, it is believed that they adsorb onto bone surfaces most probably via the calcium of hydroxyapatite crystals. Because the major factors that affect adsorption are osteoblastic activity and to a lesser extent skeletal vascularity, it is apparent that a bone scan image presents a functional display of skeletal metabolic activity. However, osteoporosis is a disorder in which gradual change in bone mass may occur over many years and, in keeping with this minor imbalance in skeletal metabolism, the bone scan appearances are usually normal. However, the scan images may appear of poor quality because of relatively low bone uptake of tracer with, on occasion, a washed-out pattern of activity in the axial and appendicular bone. It has been suggested that such a pattern occurs in severe or end-stage osteoporosis caused by markedly reduced osteoblastic activity. If kyphosis is observed on the bone scan or if there appears to be loss of spinal height with proximity of ribs to each other or increased closeness of rib cage to pelvis, then appearances suggest vertebral collapse and would be in keeping with a diagnosis of osteoporosis. Such evidence is, however, indirect and in practice a bone scan is an extremely unreliable means of diagnosing osteoporosis

  10. Bone metabolism in anorexia nervosa.

    Science.gov (United States)

    Fazeli, Pouneh K; Klibanski, Anne

    2014-03-01

    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 comorbidities 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

  11. Bone Metabolism in Anorexia Nervosa

    Science.gov (United States)

    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

  12. Zeolite A effect on calcium homeostasis in growing goats.

    Science.gov (United States)

    Schwaller, D; Wilkens, M R; Liesegang, A

    2016-04-01

    The purpose of this study was to investigate the influence of 2 different concentrations of zeolite A on calcium homeostasis. Seventeen growing goats were divided into 3 groups. Whereas the control group (5 animals) received no supplementation, 2 treatment groups were supplemented with zeolite A at either 1.2 (6 animals) or 1.6 g/kg BW (6 animals), respectively. Blood and urine samples were continually drawn and bone mineral density was measured weekly by peripheral quantitative computed tomography. After 3 wks, the animals were slaughtered and samples were taken from the rumen, duodenum, and kidneys. Plasma concentrations of phosphate ( Ussing chamber technique and quantification of RNA and protein expression of genes known to be involved in active calcium absorption did not reveal any stimulating effect of zeolite. Plasma calcium concentrations were not altered, probably because of the sufficient dietary calcium supply. However due to the effects of zeolite on 1,25 dihydroxycholecalciferol, bone metabolism and serum concentrations of phosphate and magenesium shown in the present study, potential negative long-termin effects on the animals should be considered whenever rations with zeolite are designed. PMID:27136016

  13. Fibroblast growth factor 23 and bone mineralisation

    Institute of Scientific and Technical Information of China (English)

    Yu-Chen Guo; Quan Yuan

    2015-01-01

    Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts in bone. The critical role of FGF23 in mineral ion homeostasis was first identified in human genetic and acquired rachitic diseases and has been further characterised in animal models. Recent studies have revealed that the levels of FGF23 increase significantly at the very early stages of chronic kidney disease (CKD) and may play a critical role in mineral ion disorders and bone metabolism in these patients. Our recent publications have also shown that FGF23 and its cofactor, Klotho, may play an independent role in directly regulating bone mineralisation instead of producing a systematic effect. In this review, we will discuss the new role of FGF23 in bone mineralisation and the pathophysiology of CKD-related bone disorders.

  14. Physiology and molecular characterization of metabolism related mouse models for bone disease

    OpenAIRE

    Chi, Shen

    2015-01-01

    Bone disorders are commonly associated with various metabolic diseases. Two ENU- induced mutant mouse lines were analyzed to explore the relationship between bone and metabolic phenotypes. SATB2 was proven to regulate bone development. In addition, a previously unknown role of the gene in energy metabolism was uncovered. Only a minor influence on bone homeostasis and energy metabolism could be attributed to the T720A mutation of DLL1.

  15. Implant-induced microdamage in osteoporotic bone

    Directory of Open Access Journals (Sweden)

    YU Zhi-feng

    2012-04-01

    Full Text Available 【Abstract】With the increase of elderly population, more and more implant operations need to be performed in osteoporotic bone, while different forms of microdamage will be produced in peri-implant bone intraoperatively, in-cluding high- and low-density diffuse damages, as well as linear cracks. The length and location of the microcracks are the main factors in affecting the biomechanical performance of bone. Suppression of bone remodeling by bisphosphonates may lead to microdamage accumulation, which is often accompanied with the decrease of bone strength and the increase of bone fragility. Microdamage can be repaired by bone remodeling or mineralization to maintain the strength and structural integrity. Both remo-deling and mineralization can affect the bone quality and long-term implant stability. In this paper, we make a brief summary of some important issues and research progresses in this field. Key words: Osteoporosis, postmenopausal; Bone remodeling; Aged

  16. Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling.

    Science.gov (United States)

    Kandyba, Eve; Kobielak, Krzysztof

    2014-04-01

    The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis, and progeny differentiation. During morphogenesis, Wnt signaling is well-characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previously, we described the function of the bone morphogenetic protein (BMP) signaling target gene WNT7a in intrinsic regulation of hfSCs homeostasis in vivo. Here, we investigated the role of Wnt7b, which was also intrinsically upregulated in hfSCs during physiological and precocious anagen after BMP inhibition in vivo. We demonstrated Wnt7b to be a direct target of canonical BMP signaling in hfSCs and using Wnt7b conditional gene targeting during HF morphogenesis revealed disrupted HF cycling including a shorter anagen, premature catagen onset with overall shorter hair production, and diminished HF differentiation marker expression. Additionally, we observed that postnatal ablation of Wnt7b resulted in delayed HF activation, affecting both the hair germ and bulge hfSCs but still maintaining a two-step sequence of HF stimulation. Interestingly, Wnt7b cKO hfSCs participated in reformation of the new HF bulge, but with slower self-renewal. These findings demonstrate the importance of intrinsic Wnt7b expression in hfSCs regulation and normal HF cycling and surprisingly reveal a nonredundant role for Wnt7b in the control of HF anagen length and catagen entry which was not compensated by other Wnt ligands. PMID:24222445

  17. Bone nutrients for vegetarians.

    Science.gov (United States)

    Mangels, Ann Reed

    2014-07-01

    The process of bone mineralization and resorption is complex and is affected by numerous factors, including dietary constituents. Although some dietary factors involved in bone health, such as calcium and vitamin D, are typically associated with dairy products, plant-based sources of these nutrients also supply other key nutrients involved in bone maintenance. Some research suggests that vegetarian diets, especially vegan diets, are associated with lower bone mineral density (BMD), but this does not appear to be clinically significant. Vegan diets are not associated with an increased fracture risk if calcium intake is adequate. Dietary factors in plant-based diets that support the development and maintenance of bone mass include calcium, vitamin D, protein, potassium, and soy isoflavones. Other factors present in plant-based diets such as oxalic acid and phytic acid can potentially interfere with absorption and retention of calcium and thereby have a negative effect on BMD. Impaired vitamin B-12 status also negatively affects BMD. The role of protein in calcium balance is multifaceted. Overall, calcium and protein intakes in accord with Dietary Reference Intakes are recommended for vegetarians, including vegans. Fortified foods are often helpful in meeting recommendations for calcium and vitamin D. Plant-based diets can provide adequate amounts of key nutrients for bone health. PMID:24898231

  18. Leptin therapy, insulin sensitivity, and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Gilberto Paz-Filho

    2012-01-01

    Full Text Available Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insulinemia and insulin resistance. The understanding of the effects of leptin on the glucose-insulin homeostasis will lead to the development of leptin-based therapies against diabetes and other insulin resistance syndromes. In these review, we summarize the interactions between leptin and insulin, and their effects on the glucose metabolism.

  19. Melanocortin-4 receptor-regulated energy homeostasis.

    Science.gov (United States)

    Krashes, Michael J; Lowell, Bradford B; Garfield, Alastair S

    2016-02-01

    The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular components--two antagonistically acting ligands and two cognate receptors--this phylogenetically conserved system serves as a prototype for hierarchical energy balance regulation. Over the last decade the application of conditional genetic techniques has facilitated the neuroanatomical dissection of the melanocortinergic network and identified the specific neural substrates and circuits that underscore the regulation of feeding behavior, energy expenditure, glucose homeostasis and autonomic outflow. In this regard, the melanocortin-4 receptor is a critical coordinator of mammalian energy homeostasis and body weight. Drawing on recent advances in neuroscience and genetic technologies, we consider the structure and function of the melanocortin-4 receptor circuitry and its role in energy homeostasis. PMID:26814590

  20. Bone mineral density and markers of bone turnover in patients with renal transplantation and regular hemodialysis

    Directory of Open Access Journals (Sweden)

    Samir M. Ibrahim,. Khalid H Abdel-Mageed, Magdi M El-Sharkawy

    2002-09-01

    Full Text Available Background: Decreased bone mineral density (BMD is a known complication for the uremic state antedating dialysis / renal transplantation (RTx. The issue of stabilized versus continued decrease of BMD especially on long-term basis, continues to be unresolved. Patients and Methods: !"#"hemodialysis (HD-#" $% " &'( &'(-group had been evaluated for metabolic bone changes by calcium homeostasis parameters (serum calcium, phosphorus, alkaline phosphatase "ALP" and vitamin D "calcitriol", markers of bone formation (bone alkaline phosphatase "BAP", osteocalcin "OC", N-terminal propeptide of collagen type I "PINP", bone resorption markers (pyridoline "PYL" and deoxypyridoline "DPYL", and intact parathyroid hormone (iPTH. Also, BMD had been assessed by dual energy x-ray absorptiometry (DEXA twice, at inclusion time and * ! "" Results: comparing both groups regarding calcium homeostasis, markers of bone turnover and iPTH showed non significant difference. However, there was a significant drop of BMD (as evidenced by T-score at follow up in the HD group, compared to stabilization of T-score for the RTx-group. Furthermore, annual T-score change was significantly more in HD-group, compared to RTx-group. Results also showed that, the best marker correlating with T-score annual changes and iPTH to be PINP. Irrespective of normal calcium homeostasis parameters, low BMD is a prevalent disorder among patients on regular HD and renal transplants.Conclusion: Follow up for * ! " %+ ,- ." % """"!to continued bone loss in patients on regular HD. This could raise recommendation for calcium and calcitriol supplementation, especially in the predialysis period, early post transplantation period, and continued guided replacement for those on maintenance HD. Serum PINP showed best correlations with BMD changes and iPTH and could be considered a reliable marker reflecting bone formation in those patients. Keywords: hemodialysis, renal transplantation, markers of bone

  1. Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura.

    Science.gov (United States)

    Callea, V; Comis, M; Iaria, G; Sculli, G; Morabito, F; Lombardo, V T

    1997-01-01

    In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder. PMID:9299867

  2. Regulating Subcellular Metal Homeostasis: The Key to Crop Improvement.

    Science.gov (United States)

    Bashir, Khurram; Rasheed, Sultana; Kobayashi, Takanori; Seki, Motoaki; Nishizawa, Naoko K

    2016-01-01

    Iron (Fe), zinc (Zn), manganese (Mn), and copper (Cu) are essential micronutrient mineral elements for living organisms, as they regulate essential cellular processes, such as chlorophyll synthesis and photosynthesis (Fe, Cu, and Mn), respiration (Fe and Cu), and transcription (Zn). The storage and distribution of these minerals in various cellular organelles is strictly regulated to ensure optimal metabolic rates. Alteration of the balance in uptake, distribution, and/or storage of these minerals severely impairs cellular metabolism and significantly affects plant growth and development. Thus, any change in the metal profile of a cellular compartment significantly affects metabolism. Different subcellular compartments are suggested to be linked through complex retrograde signaling networks to regulate cellular metal homeostasis. Various genes regulating cellular and subcellular metal distribution have been identified and characterized. Understanding the role of these transporters is extremely important to elaborate the signaling between various subcellular compartments. Moreover, modulation of the proteins involved in cellular metal homeostasis may help in the regulation of metabolism, adaptability to a diverse range of environmental conditions, and biofortification. Here, we review progress in the understanding of different subcellular metal transport components in plants and discuss the prospects of regulating cellular metabolism and strategies to develop biofortified crop plants. PMID:27547212

  3. The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis.

    Science.gov (United States)

    Razzaque, Mohammed S; Lanske, Beate

    2007-07-01

    Normal mineral ion homeostasis is tightly controlled by numerous endocrine factors that coordinately exert effects on intestine, kidney, and bone to maintain physiological balance. The importance of the fibroblast growth factor (FGF)-23-klotho axis in regulating mineral ion homeostasis has been proposed from recent research observations. Experimental studies suggest that 1) FGF23 is an important in vivo regulator of phosphate homeostasis, 2) FGF23 acts as a counter regulatory hormone to modulate the renal 1alpha-hydroxylase and sodium-phosphate cotransporter activities, 3) there is a trend of interrelationship between FGF23 and parathyroid hormone activities, 4) most of the FGF23 functions are conducted through the activation of FGF receptors, and 5) such receptor activation needs klotho, as a cofactor to generate downstream signaling events. These observations clearly suggest the emerging roles of the FGF23-klotho axis in maintaining mineral ion homeostasis. In this brief article, we will summarize how the FGF23-klotho axis might coordinately regulate normal mineral ion homeostasis, and how their abnormal regulation could severely disrupt such homeostasis to induce disease pathology. PMID:17592015

  4. The impact of skeletal unloading on bone formation

    Science.gov (United States)

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

    2003-01-01

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

  5. Treatment with bone marrow mesenchymal stem cells combined with plumbagin alleviates spinal cord injury by affecting oxidative stress, inflammation, apoptotis and the activation of the Nrf2 pathway.

    Science.gov (United States)

    Yang, Wencheng; Yang, Yan; Yang, Jian-Yi; Liang, Ming; Song, Jiangtao

    2016-04-01

    The aim of the present study was to investigate the protective effect exerted by bone marrow mesenchymal stem cells (BMSCs) in combination with plumbagin on spinal cord injury (SCI) and explore the mechanism behind this protective effect. Firstly, BMSCs were extracted from male Sprague-Dawley rats, cultured in vitro, and identified by hematoxylin. Sprague-Dawley rats were then randomly divided into a control group, SCI model group, BMSC-treated group, a plumbagin-treated group, and a BMSC and plumbagin-treated group. After treatment with BMSCs combined with plumbagin, a Basso, Beattie and Bresnahan (BBB) test was carried out and the spinal cord water content was examined in order to analyze the effect of BMSCs combined with plumbagin on SCI. The myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor-κB (NF-κB) p65 unit, tumor necrosis factor-α (TNF-α) levels were also detected. Moreover, nuclear factor erythroid 2‑related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)Akt, p-p38 mitogen-activated protein kinase (MAPK), and p-extracellular-signal-regulated kinase (ERK) protein expression levels were measured using western blot analysis. Treatment with BMSCs combined with plumbagin significantly improved locomotor recovery and reduced the spinal cord water content after SCI. The increased MPO, MDA, NF-κB p65 and TNF-α levels were significantly suppressed and the decreased SOD was significantly increased in SCI rats. The suppression of Nrf2, p-Akt and p-ERK, as well as the promotion of p-p38 MAPK, were reversed by treatment with BMSCs combined with plumbagin. These effects suggest that treatment with BMSCs combined with plumbagin alleviates SCI through its effects on oxidative stress, inflammation, apoptotis and activation of the Nrf2 pathway. PMID:26936518

  6. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Antonella Conforti

    Full Text Available Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs isolated from bone marrow (BM of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs at diagnosis (day+0 and during chemotherapy treatment (days: +15; +33; +78, the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs. ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001 and ability to support in vitro hematopoiesis (p = 0.04 as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.. ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present, nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment.

  7. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.

    Science.gov (United States)

    Conforti, Antonella; Biagini, Simone; Del Bufalo, Francesca; Sirleto, Pietro; Angioni, Adriano; Starc, Nadia; Li Pira, Giuseppina; Moretta, Francesca; Proia, Alessandra; Contoli, Benedetta; Genovese, Silvia; Ciardi, Claudia; Avanzini, Maria Antonietta; Rosti, Vittorio; Lo-Coco, Francesco; Locatelli, Franco; Bernardo, Maria Ester

    2013-01-01

    Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment. PMID:24244271

  8. Bone and energy metabolism parameters in professional cyclists during the Giro d'Italia 3-weeks stage race.

    Directory of Open Access Journals (Sweden)

    Giovanni Lombardi

    Full Text Available Cycling is a not weight-bearing activity and is known to induce bone resorption. Stage races are really strenuous endurance performances affecting the energy homeostasis. The recently highlighted link, in the co-regulation of bone and energy metabolism, demonstrates a central role for the equilibrium between carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to understand the acute physiological responses to a cycling stage race in terms of bone turnover and energy metabolism and the possible co-regulative mechanisms underlying their relationship. We studied nine professional cyclists engaged in 2011 Giro d'Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authority's recommendations. Bone and energy metabolism markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin and related hormones (cortisol and testosterone were measured, by Sandwich Enzyme Immunoassays, at days -1 (pre-race, 12 and 22 during the race. The power output and the energy expenditure (mean and accumulated were derived and correlated with the biochemical indexes. During the race, bone metabolism showed that an unbalance in behalf of resorption, which is enhanced, occurred along with a relative increase in the concentration of the undercarboxylated form of osteocalcin that was indirectly related to the enhanced energy expenditure, through adipokines modifications, with leptin decrease (high energy consumption and adiponectin increase (optimization of energy expenditure. The exertion due to heavy effort induced a decrease of cortisol, while testosterone levels resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism is pushed towards resorption. A possible relationship between the bone and the energy metabolisms is suggested by the relative correlations among absolute and relative concentrations

  9. RANKL, Osteopontin, and Osteoclast Homeostasis in a Hyper-Occlusion Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Cameron G.; Ito, Yoshihiro; Dangaria, Smit; Luan, Xianghong; Diekwisch, Thomas G.H. (UIC)

    2010-11-15

    The biological mechanisms that maintain the position of teeth in their sockets establish a dynamic equilibrium between bone resorption and apposition. In order to reveal some of the dynamics involved in the tissue responses towards occlusal forces on periodontal ligament (PDL) and alveolar bone homeostasis, we developed the first mouse model of hyperocclusion. Swiss-Webster mice were kept in hyperocclusion for 0, 3, 6, and 9 d. Morphological and histological changes in the periodontium were assessed using micro-computed tomography (micro-CT) and ground sections with fluorescent detection of vital dye labels. Sections were stained for tartrate-resistant acid phosphatase, and the expression of receptor activator of nuclear factor-{kappa}B ligand (RANKL) and osteopontin (OPN) was analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). Traumatic occlusion resulted in enamel surface abrasion, inhibition of alveolar bone apposition, significant formation of osteoclasts at 3, 6 and 9 d, and upregulation of OPN and RANKL. Data from this study suggest that both OPN and RANKL contribute to the stimulation of bone resorption in the hyperocclusive state. In addition, we propose that the inhibition of alveolar bone apposition by occlusal forces is an important mechanism for the control of occlusal height that might work in synergy with RANKL-induced bone resorption to maintain normal occlusion.

  10. Redox Homeostasis in Pancreatic beta Cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

    2012-01-01

    Roč. 2012, č. 2012 (2012), s. 932838. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204 Institutional support: RVO:67985823 Keywords : beta cells * reactive oxygen species homeostasis * mitochondria Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.393, year: 2012

  11. [Bone diseases].

    Science.gov (United States)

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  12. Implant-induced microdamage in osteoporotic bone.

    Science.gov (United States)

    Yu, Zhi-Feng; Tang, Ting-Ting; Qiu, Shi-Jing

    2012-01-01

    With the increase of elderly population, more and more implant operations need to be performed in osteoporotic bone, while different forms of microdamage will be produced in peri-implant bone intraoperatively, including high- and low-density diffuse damages, as well as linear cracks. The length and location of the microcracks are the main factors in affecting the biomechanical performance of bone. Suppression of bone remodeling by bisphosphonates may lead to microdamage accumulation, which is often accompanied with the decrease of bone strength and the increase of bone fragility. Microdamage can be repaired by bone remodeling or mineralization to maintain the strength and structural integrity. Both remo- deling and mineralization can affect the bone quality and long-term implant stability. In this paper, we make a brief summary of some important issues and research progresses in this field. PMID:22480676

  13. Bone Metabolism in Adolescents with Anorexia Nervosa

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often begins in the adolescent years, and decreased rates of bone mass accrual at this critical time are therefore also concerning for deficits in peak bone mass. Factors contributing to low bone density and decreased rates of bone accrual include alterations in body composition such as low BMI and lean body mass, and hormonal alterations such as hypogonadism, a nutritionally acquired resistance to growth hormone and low levels of IGF-1, relative hypercortisolemia, low levels of leptin, and increased adiponectin (for fat mass) and peptide YY. Therapeutic strategies include optimizing weight and menstrual recovery, and adequate calcium and vitamin D replacement. Oral estrogen-progesterone combination pills are not effective in increasing bone density in adolescents with AN. RhIGF-1 increases levels of bone formation markers in the short-term, while long-term effects remain to be determined. Bisphosphonates act by decreasing bone resorption, and are not optimal for use in adolescents with AN, in whom the primary defect is low bone formation. PMID:21301203

  14. Implant-induced microdamage in osteoporotic bone

    OpenAIRE

    YU Zhi-feng; Tang, Ting-ting; QIU Shi-jing

    2012-01-01

    【Abstract】With the increase of elderly population, more and more implant operations need to be performed in osteoporotic bone, while different forms of microdamage will be produced in peri-implant bone intraoperatively, in-cluding high- and low-density diffuse damages, as well as linear cracks. The length and location of the microcracks are the main factors in affecting the biomechanical performance of bone. Suppression of bone remodeling by bisphosphonates may lead...

  15. Gravity, calcium, and bone - Update, 1989

    Science.gov (United States)

    Arnaud, Sara B.; Morey-Holton, Emily

    1990-01-01

    Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

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

    Science.gov (United States)

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

    2014-05-01

    Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations. PMID:24626785

  17. Talking Bones.

    Science.gov (United States)

    Johnson, Jaclyn; Kassing, Sharon

    2002-01-01

    Describes cooperation with the Saint Louis Zoo to provide opportunities for elementary school students to learn about bones, how animals move, what they eat, and how much they grow. Uses biofacts which include bones, skulls, and other parts to make the laboratory a hands-on experience for students. (YDS)

  18. Bone Markers

    Science.gov (United States)

    ... bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is ... resorption include: N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal ...

  19. Temporal aspects of copper homeostasis and its crosstalk with hormones

    Directory of Open Access Journals (Sweden)

    Lola ePeñarrubia

    2015-04-01

    Full Text Available To cope with the dual nature of copper as being essential and toxic for cells, plants temporarily adapt the expression of copper homeostasis components to assure its delivery to cuproproteins while avoiding the interference of potential oxidative damage derived from both copper uptake and photosynthetic reactions during light hours. The circadian clock participates in the temporal organization of coordination of plant nutrition adapting metabolic responses to the daily oscillations. This timely control improves plant fitness and reproduction and holds biotechnological potential to drive increased crop yields. Hormonal pathways, including those of abscisic acid, gibberellins, ethylene, auxins, and jasmonates are also under direct clock and light control, both in mono and dicotyledons. In this review, we focus on copper transport in Arabidopsis thaliana and Oryza sativa and the presumable role of hormones in metal homeostasis matching nutrient availability to growth requirements and preventing metal toxicity. The presence of putative hormone-dependent regulatory elements in the promoters of copper transporters genes suggests hormonal regulation to match special copper requirements during plant development. Spatial and temporal processes that can be affected by hormones include the regulation of copper uptake into roots, intracellular trafficking and compartmentalisation, and long-distance transport to developing vegetative and reproductive tissues. In turn, hormone biosynthesis and signalling are also influenced by copper availability, which suggests reciprocal regulation subjected to temporal control by the central oscillator of the circadian clock. This transcriptional regulatory network, coordinates environmental and hormonal signalling with developmental pathways to allow enhanced micronutrient acquisition efficiency.

  20. Molecular Determinants of Magnesium Homeostasis: Insights from Human Disease

    Science.gov (United States)

    Alexander, R. Todd; Hoenderop, Joost G.; Bindels, René J.

    2016-01-01

    The past decade has witnessed multiple advances in our understanding of magnesium (Mg2+) homeostasis. The discovery that mutations in claudin-16/paracellin-1 or claudin-19 are responsible for familial hypomagnesemia with hypercalciuria and nephrocalcinosis provided insight into the molecular mechanisms governing paracellular transport of Mg2+. Our understanding of the transcellular movement of Mg2+ was similarly enhanced by the realization that defects in transient receptor potential melastatin 6 (TRPM6) cause hypomagnesemia with secondary hypocalcemia. This channel regulates the apical entry of Mg2+ into epithelia. In so doing, TRPM6 alters whole-body Mg2+ homeostasis by controlling urinary excretion. Consequently, investigation into the regulation of TRPM6 has increased. Acid-base status, 17β estradiol, and the immunosuppressive agents FK506 and cyclosporine affect plasma Mg2+ levels by altering TRPM6 expression. A mutation in epithelial growth factor is responsible for isolated autosomal recessive hypomagnesemia, and epithelial growth factor activates TRPM6. A defect in the γ-subunit of the Na,K-ATPase causes isolated dominant hypomagnesemia by altering TRPM6 activity through a decrease in the driving force for apical Mg2+ influx. We anticipate that the next decade will provide further detail into the control of the gatekeeper TRPM6 and, therefore, overall whole-body Mg2+ balance. PMID:18562569

  1. Development and characterization of an injectable dextrin-based hydrogel for bone regeneration

    OpenAIRE

    Dina M. Silva; Daniella L. Morgado; Delair, T; David, L; Rouif, S.; López-Lacomba, J. L.; A C Maurício; Santos, J. D.; Gama, F. M.

    2014-01-01

    Bone is a dynamic, highly vascularized tissue that remodels itself continuously over an individual ́s lifetime. It plays several important roles in maintaining homeostasis of the body systems [ 1 , 2 ] . However, this regenerative capac ity is limited and, as in the case of large bone defects, where the template for an orchestrated regeneration is absent, surgical proce dures are needed [ 2...

  2. Bone-targeted therapy for metastatic breast cancer—Where do we go from here? A commentary from the BONUS 8 meeting

    Directory of Open Access Journals (Sweden)

    Xiaofu Zhu

    2014-03-01

    Full Text Available The annual Bone and The Oncologist New Updates (BONUS 8 conference focuses on the current understanding and dilemmas in the treatment and prevention of bone metastasis in cancer, as well as novel research on bone homeostasis and cancer-induced bone loss. We present commentaries from experts for their own take on where they feel the field of bone-targeted therapies for metastatic breast cancer is moving, or needs to move, if we are to make further progress.

  3. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  4. microRNA Regulation of Peritoneal Cavity Homeostasis in Peritoneal Dialysis

    Directory of Open Access Journals (Sweden)

    Melisa Lopez-Anton

    2015-01-01

    Full Text Available Preservation of peritoneal cavity homeostasis and peritoneal membrane function is critical for long-term peritoneal dialysis (PD treatment. Several microRNAs (miRNAs have been implicated in the regulation of key molecular pathways driving peritoneal membrane alterations leading to PD failure. miRNAs regulate the expression of the majority of protein coding genes in the human genome, thereby affecting most biochemical pathways implicated in cellular homeostasis. In this review, we report published findings on miRNAs and PD therapy, with emphasis on evidence for changes in peritoneal miRNA expression during long-term PD treatment. Recent work indicates that PD effluent- (PDE- derived cells change their miRNA expression throughout the course of PD therapy, contributing to the loss of peritoneal cavity homeostasis and peritoneal membrane function. Changes in miRNA expression profiles will alter regulation of key molecular pathways, with the potential to cause profound effects on peritoneal cavity homeostasis during PD treatment. However, research to date has mainly adopted a literature-based miRNA-candidate methodology drawing conclusions from modest numbers of patient-derived samples. Therefore, the study of miRNA expression during PD therapy remains a promising field of research to understand the mechanisms involved in basic peritoneal cell homeostasis and PD failure.

  5. microRNA Regulation of Peritoneal Cavity Homeostasis in Peritoneal Dialysis

    Science.gov (United States)

    Lopez-Anton, Melisa; Bowen, Timothy; Jenkins, Robert H.

    2015-01-01

    Preservation of peritoneal cavity homeostasis and peritoneal membrane function is critical for long-term peritoneal dialysis (PD) treatment. Several microRNAs (miRNAs) have been implicated in the regulation of key molecular pathways driving peritoneal membrane alterations leading to PD failure. miRNAs regulate the expression of the majority of protein coding genes in the human genome, thereby affecting most biochemical pathways implicated in cellular homeostasis. In this review, we report published findings on miRNAs and PD therapy, with emphasis on evidence for changes in peritoneal miRNA expression during long-term PD treatment. Recent work indicates that PD effluent- (PDE-) derived cells change their miRNA expression throughout the course of PD therapy, contributing to the loss of peritoneal cavity homeostasis and peritoneal membrane function. Changes in miRNA expression profiles will alter regulation of key molecular pathways, with the potential to cause profound effects on peritoneal cavity homeostasis during PD treatment. However, research to date has mainly adopted a literature-based miRNA-candidate methodology drawing conclusions from modest numbers of patient-derived samples. Therefore, the study of miRNA expression during PD therapy remains a promising field of research to understand the mechanisms involved in basic peritoneal cell homeostasis and PD failure. PMID:26495316

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

    International Nuclear Information System (INIS)

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

  7. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  8. Homeostasis as the Mechanism of Evolution

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2015-09-01

    Full Text Available Homeostasis is conventionally thought of merely as a synchronic (same time servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology.

  9. Homeostasis as the Mechanism of Evolution.

    Science.gov (United States)

    Torday, John S

    2015-01-01

    Homeostasis is conventionally thought of merely as a synchronic (same time) servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time) mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology. PMID:26389962

  10. Thiol redox homeostasis in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Gethin J. McBean

    2015-08-01

    Full Text Available This review provides an overview of the biochemistry of thiol redox couples and the significance of thiol redox homeostasis in neurodegenerative disease. The discussion is centred on cysteine/cystine redox balance, the significance of the xc− cystine–glutamate exchanger and the association between protein thiol redox balance and neurodegeneration, with particular reference to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. The role of thiol disulphide oxidoreductases in providing neuroprotection is also discussed.

  11. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    OpenAIRE

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio; Hill, Joseph A.

    2014-01-01

    Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both tra...

  12. The cellular mechanisms of body iron homeostasis

    OpenAIRE

    MARCO T NUÑEZ; MARCO A GARATE; MIGUEL ARREDONDO; VICTORIA TAPlA; PATRICIA MUÑOZ

    2000-01-01

    Cells tightly regulate iron levels through the activity of iron regulatory proteins (IRPs) that bind to RNA motifs called iron responsive elements (IREs). When cells become iron-depleted, IRPs bind to IREs present in the mRNAs of ferritin and the transferrin receptor, resulting in diminished translation of the ferritin mRNA and increased translation of the transferrin receptor mRNA. Similarly, body iron homeostasis is maintained through the control of intestinal iron absorption. Intestinal ep...

  13. Epigenetic regulation of iron homeostasis in Arabidopsis.

    Science.gov (United States)

    Xing, Jiewen; Wang, Tianya; Ni, Zhongfu

    2015-01-01

    Iron (Fe) is one of the most important microelement required for plant growth and development because of its unique property of catalyzing oxidation/reduction reactions. Iron deficiency impairs fundamental processes which could lead to a decrease in chlorophyll production and pollen fertility, thus influencing crop productivity and quality. However, iron in excess is toxic to the cell and is harmful to the plant. To exactly control the iron content in all tissues, plants have evolved many strategies to regulate iron homeostasis, which refers to 2 successive steps: iron uptake at the root surface, and iron distribution in vivo. In the last decades, a number of transporters and regulatory factors involved in this process have been isolated and identified. To cope with the complicated flexible environmental conditions, plants apply diverse mechanisms to regulate the expression and activity of these components. One of the most important mechanisms is epigenetic regulation of iron homeostasis. This review has been presented to provide an update on the information supporting the involvement of histone modifications in iron homeostasis and possible future course of the field. PMID:26313698

  14. Regulation of energy homeostasis via GPR120

    Directory of Open Access Journals (Sweden)

    Atsuhiko eIchimura

    2014-07-01

    Full Text Available Free fatty acids (FFAs are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs, activate intracellular signaling and exert physiological functions via these GPCRs. GPR120 (also known as free fatty acid receptor 4, FFAR4 is activated by unsaturated medium- to long-chain FFAs and has a critical role in various physiological homeostasis mechanisms such as incretin hormone secretion, food preference, anti-inflammation and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat in white adipose tissue and regulates the whole body energy homeostasis in both humans and rodents. Genetic study in human identified the loss-of-functional mutation of GPR120 associated with obesity and insulin resistance. In addition, dysfunction of GPR120 has been linked as a novel risk factor for diet-induced obesity. This review aims to provide evidence from the recent development in physiological function of GPR120 and discusses its functional roles in regulation of energy homeostasis and its potential as drug targets.

  15. Epigenetic regulation of iron homeostasis in Arabidopsis

    Science.gov (United States)

    Xing, Jiewen; Wang, Tianya; Ni, Zhongfu

    2015-01-01

    Iron (Fe) is one of the most important microelement required for plant growth and development because of its unique property of catalyzing oxidation/reduction reactions. Iron deficiency impairs fundamental processes which could lead to a decrease in chlorophyll production and pollen fertility, thus influencing crop productivity and quality. However, iron in excess is toxic to the cell and is harmful to the plant. To exactly control the iron content in all tissues, plants have evolved many strategies to regulate iron homeostasis, which refers to 2 successive steps: iron uptake at the root surface, and iron distribution in vivo. In the last decades, a number of transporters and regulatory factors involved in this process have been isolated and identified. To cope with the complicated flexible environmental conditions, plants apply diverse mechanisms to regulate the expression and activity of these components. One of the most important mechanisms is epigenetic regulation of iron homeostasis. This review has been presented to provide an update on the information supporting the involvement of histone modifications in iron homeostasis and possible future course of the field. PMID:26313698

  16. TCR down-regulation controls T cell homeostasis

    DEFF Research Database (Denmark)

    Boding, Lasse; Bonefeld, Charlotte Menné; Nielsen, Bodil L;

    2009-01-01

    TCR and cytokine receptor signaling play key roles in the complex homeostatic mechanisms that maintain a relative stable number of T cells throughout life. Despite the homeostatic mechanisms, a slow decline in naive T cells is typically observed with age. The CD3gamma di-leucine-based motif...... was caused by the combination of reduced thymic output, decreased T cell apoptosis, and increased transition of naive T cells to memory T cells. Experiments with bone marrow chimeric mice confirmed that the CD3gammaLLAA mutation exerted a T cell intrinsic effect on T cell homeostasis that resulted in...... controls TCR down-regulation and plays a central role in fine-tuning TCR expression and signaling in T cells. In this study, we show that the age-associated decline of naive T cells is strongly accelerated in CD3gammaLLAA knock-in mice homozygous for a double leucine to alanine mutation in the CD3gamma di...

  17. Hypothalamic AMPK as a Regulator of Energy Homeostasis.

    Science.gov (United States)

    Huynh, My Khanh Q; Kinyua, Ann W; Yang, Dong Joo; Kim, Ki Woo

    2016-01-01

    Activated in energy depletion conditions, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and regulator in both central nervous system and peripheral organs. Hypothalamic AMPK restores energy balance by promoting feeding behavior to increase energy intake, increasing glucose production, and reducing thermogenesis to decrease energy output. Besides energy state, many hormones have been shown to act in concert with AMPK to mediate their anorexigenic and orexigenic central effects as well as thermogenic influences. Here we explore the factors that affect hypothalamic AMPK activity and give the underlying mechanisms for the role of central AMPK in energy homeostasis together with the physiological effects of hypothalamic AMPK on energy balance restoration. PMID:27547453

  18. Hypothalamic AMPK as a Regulator of Energy Homeostasis

    Science.gov (United States)

    Huynh, My Khanh Q.; Kinyua, Ann W.; Yang, Dong Joo

    2016-01-01

    Activated in energy depletion conditions, AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and regulator in both central nervous system and peripheral organs. Hypothalamic AMPK restores energy balance by promoting feeding behavior to increase energy intake, increasing glucose production, and reducing thermogenesis to decrease energy output. Besides energy state, many hormones have been shown to act in concert with AMPK to mediate their anorexigenic and orexigenic central effects as well as thermogenic influences. Here we explore the factors that affect hypothalamic AMPK activity and give the underlying mechanisms for the role of central AMPK in energy homeostasis together with the physiological effects of hypothalamic AMPK on energy balance restoration. PMID:27547453

  19. Impact of bone graft harvesting techniques on bone formation and graft resorption

    DEFF Research Database (Denmark)

    Saulacic, Nikola; Bosshardt, Dieter D; Jensen, Simon S;

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  1. Bone Tumor

    Science.gov (United States)

    ... the knee in either the femur (thigh) or tibia (shinbone). Other common locations include the hip and ... bone that is weakened by a tumor to fracture, or break. This may be severely painful. Occasionally, ...

  2. Your Bones

    Science.gov (United States)

    ... a fall! If you play sports like football, soccer, lacrosse, or ice hockey, always wear all the ... to strengthen your bones is through exercise like running, jumping, dancing, and playing sports. Take these steps ...

  3. Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration

    OpenAIRE

    Huber, Bruno C.; Grabmaier, Ulrich; Brunner, Stefan

    2014-01-01

    Parathyroid hormone (PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the...

  4. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    OpenAIRE

    Jean-Christophe Brisset; Hoff, Benjamin A.; Thomas L Chenevert; Jacobson, Jon A.; Boes, Jennifer L.; Stefanie Galbán; Alnawaz Rehemtulla; Timothy D. Johnson; Pienta, Kenneth J.; Galbán, Craig J.; Meyer, Charles R.; Timothy Schakel; Klaas Nicolay; Alva, Ajjai S.; Maha Hussain

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI a...

  5. Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/β-Catenin Dependent Mechanism

    OpenAIRE

    Francesca Wannenes; Vincenza Papa; Greco, Emanuela A.; Rachele Fornari; Chiara Marocco; Carlo Baldari; Luigi Di Luigi; Gian Pietro Emerenziani; Eleonora Poggiogalle; Laura Guidetti; Donini, Lorenzo M.; Andrea Lenzi; Silvia Migliaccio

    2014-01-01

    Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by...

  6. The molecular physiology of uric acid homeostasis.

    Science.gov (United States)

    Mandal, Asim K; Mount, David B

    2015-01-01

    Uric acid, generated from the metabolism of purines, has proven and emerging roles in human disease. Serum uric acid is determined by production and the net balance of reabsorption or secretion by the kidney and intestine. A detailed understanding of epithelial absorption and secretion of uric acid has recently emerged, aided in particular by the results of genome-wide association studies of hyperuricemia. Novel genetic and regulatory networks with effects on uric acid homeostasis have also emerged. These developments promise to lead to a new understanding of the various diseases associated with hyperuricemia and to novel, targeted therapies for hyperuricemia. PMID:25422986

  7. Granulocyte-macrophage colony-stimulating factor and pulmonary surfactant homeostasis.

    Science.gov (United States)

    Reed, J A; Whitsett, J A

    1998-01-01

    Pulmonary surfactant lining the alveolus of the lung is critical to postnatal adaptation to air breathing. Precise concentrations of surfactant proteins and lipids are maintained in the alveolar space by a careful balance among synthesis, recycling, and catabolism. Pulmonary alveolar proteinosis is a rare pulmonary disease associated with accumulation of surfactant lipids and proteins in the alveolar spaces. Recent work with transgenic mice demonstrated that disruption of the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) or the common beta-subunit of the GM-CSF receptor caused alveolar proteinosis that was histologically similar to that seen in human patients. The defect in surfactant homeostasis is caused by decreased surfactant clearance, mediated (at least in part) by dysfunction of the alveolar macrophage. Local production of GM-CSF corrects the alveolar proteinosis in the GM-CSF knockout mouse. Likewise, transplantation of wild-type bone marrow cells expressing the common beta-chain of the GM-CSF receptor restores surfactant homeostasis in the GM-CSF receptor knockout mouse. These studies demonstrate the previously unanticipated role of GM-CSF signaling in surfactant homeostasis, mediated (at least in part) by its actions on the clearance of surfactant lipids and proteins by the alveolar macrophage. These findings may have important implications for the diagnosis and treatment of pulmonary alveolar proteinosis syndromes in humans. PMID:9686680

  8. Pleiotropic activity of lysophosphatidic acid in bone metastasis.

    Science.gov (United States)

    Peyruchaud, Olivier; Leblanc, Raphael; David, Marion

    2013-01-01

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

  9. MAVS maintains mitochondrial homeostasis via autophagy.

    Science.gov (United States)

    Sun, Xiaofeng; Sun, Liwei; Zhao, Yuanyuan; Li, Ying; Lin, Wei; Chen, Dahua; Sun, Qinmiao

    2016-01-01

    Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS-mediated antiviral signalling contributes to mitochondrial homeostasis. Here we show that the activation of MAVS is sufficient to induce autophagic signalling, which may mediate the turnover of the damaged mitochondria. Importantly, we find MAVS directly interacts with LC3 through its LC3-binding motif 'YxxI', suggesting that MAVS might act as an autophagy receptor to mediate mitochondrial turnover upon excessive activation of RLR signalling. Furthermore, we provide evidence that both MAVS self-aggregation and its interaction with TRAF2/6 proteins are important for MAVS-mediated mitochondrial turnover. Collectively, our findings suggest that MAVS acts as a potential receptor for mitochondria-associated autophagic signalling to maintain mitochondrial homeostasis. PMID:27551434

  10. Apoptosis signaling pathways and lymphocyte homeostasis

    Institute of Scientific and Technical Information of China (English)

    Guangwu Xu; Yufang Shi

    2007-01-01

    It has been almost three decades since the term "apoptosis" was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways of apoptotic cell death induction: extrinsic signaling through death receptors that leads to the formation of the death-inducing signaling complex (DISC), and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.

  11. Plant transporters involved in heavy metal homeostasis

    Directory of Open Access Journals (Sweden)

    Dorina Podar

    2010-12-01

    Full Text Available Transition metal ions (predominately manganese, iron, cobalt, nickel, copper and zinc havean array of catalytic and regulatory roles in the growth and development of all living organisms.However, an excess of these metal ions can also be toxic to any life form and therefore every cell andwhole organism needs to maintain the concentration of these essential nutrient metals within a narrowrange: a process known as metal homeostasis. Heavy metal ions are taken up into cells by selectivetransporters and as they cannot be degraded, the “desired” levels of metal ions are achieved by anumber of strategies that involve: chelation, sequestration and export out of the cell. Cation DiffusionFacilitators (CDF is a large family of transporters involved in maintaining the cytosolic metalconcentration. They transport different heavy metal divalent ions, but exhibit main affinity for zinc, ironand manganese. Metal Tolerance Proteins (MTPs are a subfamily of the Cation Diffusion Facilitator (CDFfamily found in plants. There has been much interest in these heavy metal transporters in order toprovide an insight into plant metal homeostasis, which has significant implications in human health andphytoremediation. Although data regarding the CDFs/MTPs mechanism is gathering there is still littleinformation with respect to metal selectivity determinants.

  12. Regulation of neuronal chloride homeostasis by neuromodulators.

    Science.gov (United States)

    Mahadevan, Vivek; Woodin, Melanie A

    2016-05-15

    KCC2 is the central regulator of neuronal Cl(-) homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G-protein-coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn(2+) receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5-hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A-type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR-signals are novel endogenous Cl(-) extrusion enhancers that may regulate KCC2 function. PMID:26876607

  13. Consciousness, endogenous generation of goals and homeostasis

    Science.gov (United States)

    Tsitolovsky, Lev E.

    2015-08-01

    Behaviour can be both unpredictable and goal directed, as animals act in correspondence with their motivation. Motivation arises when neurons in specific brain areas leave the state of homeostatic equilibrium and are injured. The basic goal of organisms and living cells is to maintain their life and their functional state is optimal if it does not lead to physiological damage. This can somehow be sensed by neurons and the occurrence of damage elicits homeostatic protection to recover excitability and the ability to produces spikes. It can be argued that the neuron's activity is guided on the scale of "damage-protection" and it behaves as an object possessing minimum awareness. The approach of death increases cellular efforts to operate. Thus, homeostasis may evidently produce both maintenance of life and will. The question is - how does homeostasis reach the optimum? We have no possibility of determining how the cell evaluates its own states, e.g. as "too little free energy" or in terms of "threat" to life. In any case, the approach of death increases cellular efforts to operate. For the outside observer, this is reminiscent of intentional action and a manifestation of will.

  14. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  15. Transient Intermittent Hypoxia Exposure Disrupts Neonatal Bone Strength

    Science.gov (United States)

    Kim, Gyuyoup; Elnabawi, Omar; Shin, Daehwan; Pae, Eung-Kwon

    2016-01-01

    A brief intermittent hypoxia (IH, ambient O2 levels alternating between room air and 12% O2) for 1 h immediately after birth resulted in pancreatic islet dysfunction associated with zinc deficiency as previously reported. We hypothesized that IH exposure modulates zinc homeostasis in bone as well, which leads to increased bone fragility. To test this hypothesis, we used neonatal rats and human osteoblasts (HObs). To examine IH influences on osteoblasts devoid of neural influences, we quantified amounts of alkaline phosphatase and mineralization in IH-treated HObs. Bones harvested from IH-treated animals showed significantly reduced hardness and elasticity. The IH group also showed discretely decreased levels of alkaline phosphatase and mineralization amounts. The IH group showed a decreased expression of ZIP8 or Zrt and Irt-like protein 8 (a zinc uptake transporter), Runx2 (or Runt-related transcription factor 2, a master protein in bone formation), Collagen-1 (a major protein comprising the extracellular matrix of the bone), osteocalcin, and zinc content. When zinc was eliminated from the media containing HObs using a zinc chelate and added later with zinc sulfate, Runx2, ZIP8, and osteocalcin expression decreased first, and recovered with zinc supplementation. Adenovirus-mediated ZIP8 over-expression in osteoblasts increased mineralization significantly as well. We conclude that IH impairs zinc homeostasis in bones and osteoblasts, and that such disturbances decrease bone strength, which can be recovered by zinc supplementation. PMID:27014665

  16. Bone mass and bone metabolic indices in male master rowers.

    Science.gov (United States)

    Śliwicka, Ewa; Nowak, Alicja; Zep, Wojciech; Leszczyński, Piotr; Pilaczyńska-Szcześniak, Łucja

    2015-09-01

    The purpose of this study was to assess bone mass and bone metabolic indices in master athletes who regularly perform rowing exercises. The study was performed in 29 men: 14 master rowers and 15 non-athletic, body mass index-matched controls. Dual-energy X-ray absorptiometry measurements of the areal bone mineral density (aBMD) were performed for the total body, regional areas (arms, total forearms, trunk, thoracic spine, pelvis, and legs), lumbar spine (L1-L4), left hip (total hip and femoral neck), and forearm (33 % radius of the dominant and nondominant forearm). Serum concentrations of osteocalcin, collagen type I cross-linked C-telopeptide, visfatin, resistin, insulin, and glucose were determined. Comparative analyses showed significantly lower levels of body fat and higher lean body mass values in the rowers compared to the control group. The rowers also had significantly higher values of total and regional (left arm, trunk, thoracic spine, pelvis, and leg) BMD, as well as higher BMD values for the lumbar spine and the left hip. There were significant differences between the groups with respect to insulin, glucose, and the index of homeostasis model assessment insulin resistance. In conclusion, the systematic training of master rowers has beneficial effects on total and regional BMD and may be recommended for preventing osteoporosis. PMID:25224128

  17. Diabetes mellitus related bone metabolism and periodontal disease

    Institute of Scientific and Technical Information of China (English)

    Ying-Ying Wu; E Xiao; Dana T Graves

    2015-01-01

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

  18. Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness - A Case Study on Osteoporosis Rat Bone.

    Science.gov (United States)

    Wu, Yuchin; Adeeb, Samer; Doschak, Michael R

    2015-01-01

    Micro-computed tomography (Micro-CT) images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone microarchitectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA) can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of Micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived grayscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two- and three-dimensional bone microarchitecture from sham and ovariectomized (OVX) rats (n = 10/group). A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA, because Micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three-dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation, and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading. PMID:26042089

  19. Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness - A Case Study on Osteoporosis Rat Bone

    Directory of Open Access Journals (Sweden)

    Yuchin eWu

    2015-05-01

    Full Text Available Micro-computed tomography images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone micro-architectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived greyscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two and three dimensional bone microarchitecture from sham and ovariectomized (OVX rats (n=10/group. A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA because micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading.

  20. Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA.

    Science.gov (United States)

    Li, Shuai; Dislich, Bastian; Brakebusch, Cord H; Lichtenthaler, Stefan F; Brocker, Thomas

    2015-11-01

    Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation. PMID:26408665

  1. Bone lesion biopsy

    Science.gov (United States)

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

  2. What Is Bone?

    Science.gov (United States)

    ... by your browser. Home Bone Basics What Is Bone? Publication available in: PDF (57 KB) Related Resources ... Men, and Osteoporosis Osteoporosis Prevention For Your Information Bone Remodeling Throughout life, bone is constantly renewed through ...

  3. Calcium and bones

    Science.gov (United States)

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

  4. Facts about Broken Bones

    Science.gov (United States)

    ... White House Lunch Recipes The Facts About Broken Bones KidsHealth > For Kids > The Facts About Broken Bones ... through the skin . continue What Happens When a Bone Breaks? It hurts to break a bone! It's ...

  5. Bone biopsy (image)

    Science.gov (United States)

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

  6. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... is sent to a lab for examination. Bone biopsy may also be done under general anesthesia to ... remove the bone can be done if the biopsy exam shows that there is an abnormal growth ...

  7. Targeting one carbon metabolism with an antimetabolite disrupts pyrimidine homeostasis and induces nucleotide overflow

    OpenAIRE

    Ser, Zheng; GAO, XIA; Johnson, Christelle; Mehrmohamadi, Mahya; Liu, Xiaojing; Li, SiQi; Locasale, Jason W.

    2016-01-01

    Anti-metabolite agents that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used anti-metabolite therapeutic with varying efficacy, induces specific alterations to nucleotide metabolism by disrupting pyrimidine homeostasis. An integrative metabolomics analysis of ...

  8. Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

    OpenAIRE

    Olde Engberink, Rik H.G.; Rorije, Nienke M.G.; Homan van der Heide, Jaap J.; van den Born, Bert-Jan H.; Vogt, Liffert

    2014-01-01

    Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycos...

  9. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    DEFF Research Database (Denmark)

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K;

    2013-01-01

    Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derive...... to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway. DOI:http://dx.doi.org/10.7554/eLife.00953.001....

  10. Helicobacter pylori Colonization Ameliorates Glucose Homeostasis in Mice through a PPAR γ-Dependent Mechanism

    OpenAIRE

    Josep Bassaganya-Riera; Maria Gloria Dominguez-Bello; Barbara Kronsteiner; Adria Carbo; Pinyi Lu; Monica Viladomiu; Mireia Pedragosa; Xiaoying Zhang; Sobral, Bruno W.; Mane, Shrinivasrao P.; Mohapatra, Saroj K.; Horne, William T.; Guri, Amir J.; Michael Groeschl; Gabriela Lopez-Velasco

    2012-01-01

    Background: There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI) interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag− strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI stat...

  11. Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

    OpenAIRE

    Hipkiss, Alan R; Cartwright, Stephanie P.; Bromley, Clare; Gross, Stephane R.; Bill, Roslyn M.

    2013-01-01

    The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s ...

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

    Science.gov (United States)

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

  13. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    International Nuclear Information System (INIS)

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  14. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    Energy Technology Data Exchange (ETDEWEB)

    Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bretschi, Maren; Bäuerle, Tobias [Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Hillengass, Jens [Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Bendl, Rolf [Medical Informatics, Heilbronn University, Max-Planck-Strasse 39, 74081 Heilbronn, Germany and Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2013-12-15

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  15. Pathophysiologic basics and diagnostic limits of conventional bone scanning

    International Nuclear Information System (INIS)

    Normal bone scan demonstrates the physiological regional bone formation rate, which is related to bone remodeling and maintenance of calcium homeostasis. Osteotrope radiopharmaceuticals can be used as a perfusion marker as well as a marker of regional bone formation rate. Local hyperperfusion without increased bone formation is seen in disuse atrophy and reflex sympathic dystrophy, which are difficult to discriminate, local hypoperfusion is responsible for false negative results in osteomyelitis. A local increased bone formation rate is the substrate of a positive finding in bone fracture, inflammation, tumors, metastases and other lesions. In direct comparison with other imaging modalities (MRT, scintigraphy with non-osteotrope radiopharmaceutical and PET, but not CT and multislice-CT), planar bone scintigraphy shows an unexpected deficiency in sensitivity, which can be almost or completely overcome by using SPECT or even better 18F-fluoride PET. These techniques will also improve specificity, which still is a weak point of bone scanning, despite improved imaging performance and a huge experience in this field. The introduction of SPECT/CT und PET/CT in bone scanning will be even more desirable for this reason. (orig.)

  16. A Brief Review of Bone Adaptation to Unloading

    Institute of Scientific and Technical Information of China (English)

    Ping Zhang; Kazunori Hamamura; Hiroki Yokota

    2008-01-01

    Weight-bearing bone is constantly adapting its structure and function to mechanical environments. Loading through routine exercises stimulates bone formation and prevents bone loss, but unloading through bed rest and cast immobilization as well as exposure to weightlessness during spaceflight reduces its mass and strength. In order to elucidate the mechanism underlying unloading-driven bone adaptation, ground-based in vitro and in vivo analyses have been conducted using rotating cell culturing and hindlimb suspension. Focusing on gene expression studies in osteoblasts and hindlimb suspension studies, this minireview introduces our recent understanding on bone homeostasis under weightlessness in space. Most of the existing data indicate that unloading has the opposite effects to loading through common signaling pathways. However, a question remains as to whether any pathway unique to unloading (and not to loading) may exist.

  17. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  18. PACAP in the Defense of Energy Homeostasis.

    Science.gov (United States)

    Rudecki, Alexander P; Gray, Sarah L

    2016-09-01

    The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) mediates diverse physiology from neuroprotection to thermoregulation. PACAP is well established as a master regulator of the stress response, regulating psychological and physiological equilibrium via the autonomic nervous system. Neuroanatomical and functional evidence support a role for PACAP in energy metabolism, including thermogenesis, activity, mobilization of energy stores, and appetite. Through integration of this evidence we suggest PACAP be included in the growing list of neuropeptides that mediate energy homeostasis. Future work to uncover the intricacies of PACAP expression and the molecular pathways responsible for PACAP signaling may show potential for this neuropeptide as a therapeutic target as well as further elucidate the complex neuroanatomical networks involved in defending energy balance. PMID:27166671

  19. Environmental stresses disrupt telomere length homeostasis.

    Directory of Open Access Journals (Sweden)

    Gal Hagit Romano

    Full Text Available Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues.

  20. Iron homeostasis and nutritional iron deficiency.

    Science.gov (United States)

    Theil, Elizabeth C

    2011-04-01

    Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins encoded in iron responsive element (IRE)-mRNA. The noncoding IRE-mRNA structures bind protein repressors, IRP1 or 2, during iron deficiency. Integration of the IRE-RNA in translation regulators (near the cap) or turnover elements (after the coding region) increases iron uptake (DMT1/TRF1) or decreases iron storage/efflux (FTN/FPN) when IRP binds. An antioxidant response element in FTN DNA binds Bach1, a heme-sensitive transcription factor that coordinates expression among antioxidant response proteins like FTN, thioredoxin reductase, and quinone reductase. FTN, an antioxidant because Fe(2+) and O(2) (reactive oxygen species generators) are consumed to make iron mineral, is also a nutritional iron concentrate that is an efficiently absorbed, nonheme source of iron from whole legumes. FTN protein cages contain thousands of mineralized iron atoms and enter cells by receptor-mediated endocytosis, an absorption mechanism distinct from transport of nonheme iron salts (ferrous sulfate), iron chelators (ferric-EDTA), or heme. Recognition of 2 nutritional nonheme iron sources, small and large (FTN), will aid the solution of iron deficiency, a major public health problem, and the development of new policies on iron nutrition. PMID:21346101

  1. New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

    International Nuclear Information System (INIS)

    cortical bone. • TCDD does not affect the bones of Ahr–/– mice

  2. 应用骨减压治疗恢复小儿胫骨结节骨软骨病患儿下肢运动功能%Application of bone decompression in the treatment and repair of affected lower limbers after osteochondrosis of tibial tuberosity

    Institute of Scientific and Technical Information of China (English)

    马达; 薛克修

    2002-01-01

    @@ Background:Osteochondrosis of tibial tuberosity is common among older children esp.children loving sport.For children with light symptoms,osteochondrosis will recovery voluntarily after a long time.Activity should be restricted in children with severe symptoms.Therapeutic effect of fixation of lower limbers or surgery are ineffective.Children during active phase will be affected psychosomatically.Objective:To introduce application of bone decompression in the treatment of ostochondrosis of tibial tuberosity.

  3. Bone growth in electric fields

    International Nuclear Information System (INIS)

    Research performed in several laboratories has shown that artificially induced currents affect bone growth. Studies of various current characteristics produced by implanted electrodes indicate that continuous dc, interrupted dc, and asymmetric ac all increase osteogenesis at the cathode. Stimulation from an externally applied balanced ac field was reported to reduce bone loss from disuse. The purpose of the study being reported here was to examine the influence of a uniform ac electric field on the normal skeletal growth pattern of rats. Juvenile rats received whole body exposure to uniform, vertical 60-Hz electric fields at 100 kV/m for 30 days. There were no marked alterations in the general growth pattern of the exposed animals compared to controls maintained under similar conditions. Bone growth rate, measured by tetracycline labeling, morphology of lumbar vertebrae and tibias and cortical bone area and marrow space area of tibias were not disturbed by exposure to the electric fields. (author)

  4. Bone disease in anorexia nervosa.

    Science.gov (United States)

    Dede, Anastasia D; Lyritis, George P; Tournis, Symeon

    2014-01-01

    Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task. PMID:24722126

  5. ROS Homeostasis Regulates Somatic Embryogenesis via the Regulation of Auxin Signaling in Cotton.

    Science.gov (United States)

    Zhou, Ting; Yang, Xiyan; Guo, Kai; Deng, Jinwu; Xu, Jiao; Gao, Wenhui; Lindsey, Keith; Zhang, Xianlong

    2016-06-01

    Somatic embryogenesis (S.E.) is a versatile model for understanding the mechanisms of plant embryogenesis and a useful tool for plant propagation. To decipher the intricate molecular program and potentially to control the parameters affecting the frequency of S.E., a proteomics approach based on two-dimensional gel electrophoresis (2-DE) combined with MALDI-TOF/TOF was used. A total of 149 unique differentially expressed proteins (DEPs) were identified at different stages of cotton S.E. compared with the initial control (0 h explants). The expression profile and functional annotation of these DEPs revealed that S.E. activated stress-related proteins, including several reactive oxygen species (ROS)-scavenging enzymes. Proteins implicated in metabolic, developmental, and reproductive processes were also identified. Further experiments were performed to confirm the role of ROS-scavenging enzymes, suggesting the involvement of ROS homeostasis during S.E. in cotton. Suppressing the expression of specifically identified GhAPX proteins resulted in the inhibition of dedifferentiation. Accelerated redifferentiation was observed in the suppression lines of GhAPXs or GhGSTL3 in parallel with the alteration of endogenous ascorbate metabolism and accumulation of endogenous H2O2 content. Moreover, disrupting endogenous redox homeostasis through the application of high concentrations of DPI, H2O2, BSO, or GSH inhibited the dedifferentiation of cotton explants. Mild oxidation induced through BSO treatment facilitated the transition from embryogenic calluses (ECs) to somatic embryos. Meanwhile, auxin homeostasis was altered through the perturbation of ROS homeostasis by chemical treatments or suppression of ROS-scavenging proteins, along with the activating/suppressing the transcription of genes related to auxin transportation and signaling. These results show that stress responses are activated during S.E. and may regulate the ROS homeostasis by interacting with auxin signaling

  6. A conceptual framework for homeostasis: development and validation.

    Science.gov (United States)

    McFarland, Jenny; Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

    2016-06-01

    We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. PMID:27105740

  7. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Science.gov (United States)

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  8. Bone scintigraphy in drug addiction

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Majano, V.; Miskew, D.; Sansi, P.

    1981-01-01

    In 22 drug addicts, the clinical diagnosis of osteomyelitis and/or septic arthritis was suspected because of symptoms of sepsis and pain in various locations. All patients underwent bone scintigraphy with 17-20 mCi of /sup 99/sup(m)Tc labeling either pyrophosphate or methylene diphosphonate. Whole body and spot scans located the area of disease in most patients. This permitted biopsy of the affected area when the pathogen recurs. One of the two patients whose scintigrams were normal was on adequate treatment before the bone scintigram and the other was on oxacillin. Radiographs of the affected areas were normal, which indicates bone scintigraphy should be preferred to radiography in the early diagnosis of osseous infections.

  9. Bone scintigraphy in drug addiction

    International Nuclear Information System (INIS)

    In 22 drug addicts, the clinical diagnosis of osteomyelitis and/or septic arthritis was suspected because of symptoms of sepsis and pain in various locations. All patients underwent bone scintigraphy with 17-20 mCi of 99sup(m)Tc labeling either pyrophosphate or methylene diphosphonate. Whole body and spot scans located the area of disease in most patients. This permitted biopsy of the affected area when the pathogen recurs. One of the two patients whose scintigrams were normal was on adequate treatment before the bone scintigram and the other was on oxacillin. Radiographs of the affected areas were normal, which indicates bone scintigraphy should be preferred to radiography in the early diagnosis of osseous infections. (orig.)

  10. Fluoride inhibits the response of bone cells to mechanical loading

    NARCIS (Netherlands)

    H.M.E. Willems; E.G.H.M. van den Heuvel; S. Castelein; J. Keverling Buisman; A.L.J.J. Bronckers; A.D. Bakker; J. Klein-Nulend

    2011-01-01

    The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-respon

  11. Mechanisms involved in cellular ceramide homeostasis

    Directory of Open Access Journals (Sweden)

    Hussain M

    2012-07-01

    Full Text Available Abstract Sphingolipids are ubiquitous and critical components of biological membranes. Their biosynthesis starts with soluble precursors in the endoplasmic reticulum and culminates in the Golgi complex and plasma membrane. Ceramides are important intermediates in the biosynthesis of sphingolipids, such as sphingomyelin, and their overload in the membranes is injurious to cells. The major product of ceramide metabolism is sphingomyelin. We observed that sphingomyelin synthase (SMS 1 or SMS2 deficiencies significantly decreased plasma and liver sphingomyelin levels. However, SMS2 but not SMS1 deficiency increased plasma ceramides. Surprisingly, SMS1 deficiency significantly increased glucosylceramide and ganglioside GM3, but SMS2 deficiency did not. To explain these unexpected findings about modest to no significant changes in ceramides and increases in other sphingolipids after the ablation of SMS1, we hypothesize that cells have evolved several organelle specific mechanisms to maintain ceramide homeostasis. First, ceramides in the endoplasmic reticulum membranes are controlled by its export to Golgi by protein mediated transfer. Second, in the Golgi, ceramide levels are modulated by their enzymatic conversion to different sphingolipids such as sphingomyelin, and glucosylceramides. Additionally, these sphingolipids can become part of triglyceride-rich apolipoprotein B-containing lipoproteins and be secreted. Third, in the plasma membrane ceramide levels are maintained by ceramide/sphingomyelin cycle, delivery to lysosomes, and efflux to extracellular plasma acceptors. All these pathways might have evolved to ensure steady cellular ceramide levels.

  12. Breast milk, microbiota, and intestinal immune homeostasis.

    Science.gov (United States)

    Walker, W Allan; Iyengar, Rajashri Shuba

    2015-01-01

    Newborns adjust to the extrauterine environment by developing intestinal immune homeostasis. Appropriate initial bacterial colonization is necessary for adequate intestinal immune development. An environmental determinant of adequate colonization is breast milk. Although the full-term infant is developmentally capable of mounting an immune response, the effector immune component requires bacterial stimulation. Breast milk stimulates the proliferation of a well-balanced and diverse microbiota, which initially influences a switch from an intrauterine TH2 predominant to a TH1/TH2 balanced response and with activation of T-regulatory cells by breast milk-stimulated specific organisms (Bifidobacteria, Lactobacillus, and Bacteroides). As an example of its effect, oligosaccharides in breast milk are fermented by colonic bacteria producing an acid milieu for bacterial proliferation. In addition, short-chain fatty acids in breast milk activate receptors on T-reg cells and bacterial genes, which preferentially mediate intestinal tight junction expression and anti-inflammation. Other components of breast milk (defensins, lactoferrin, etc.) inhibit pathogens and further contribute to microbiota composition. The breast milk influence on initial intestinal microbiota also prevents expression of immune-mediated diseases (asthma, inflammatory bowel disease, type 1 diabetes) later in life through a balanced initial immune response, underscoring the necessity of breastfeeding as the first source of nutrition. PMID:25310762

  13. Gravity and positional homeostasis of the cell

    Science.gov (United States)

    Nace, G. W.

    1983-01-01

    The effect of gravity upon cytoplasmic aggregates of the size present in eggs and upon cells is investigated. An expression is developed to describe the tendency of torque to rotate the egg and reorganize its constituents. This expression provides the net torque resulting from buoyancy and gravity acting upon a dumbbell-shaped cell, with heavy and light masses at either end and floating in a medium. Torques of approximately 2.5 x 10 to the -13th to 0.85 dyne-cm are found to act upon cells ranging from 6.4 microns to 31 mm (chicken egg). It is noted that cells must expend energy to maintain positional homeostasis against gravity, as demonstrated by results from Skylab 3, where tissue cultures used 58 percent more glucose on earth than in space. The implications for developmental biology, physiology, genetics, and evolution are discussed. It is argued that at the cellular and tissue levels the concept of gravity receptors may be unnecessary.

  14. DYSREGULATION OF ION HOMEOSTASIS BY ANTIFUNGAL AGENTS

    Directory of Open Access Journals (Sweden)

    RajiniRao

    2012-04-01

    Full Text Available Ion signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose dependent Ca2+ burst and long lasting pH changes in the model yeast S. cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.

  15. Cellular Auxin Homeostasis:Gatekeeping Is Housekeeping

    Institute of Scientific and Technical Information of China (English)

    Michel Ruiz Rosquete; Elke Barbez; Jürgen Kleine-Vehn

    2012-01-01

    The phytohormone auxin is essential for plant development and contributes to nearly every aspect of the plant life cycle.The spatio-temporal distribution of auxin depends on a complex interplay between auxin metabolism and cell-to-cell auxin transport.Auxin metabolism and transport are both crucial for plant development;however,it largely remains to be seen how these processes are integrated to ensure defined cellular auxin levels or even gradients within tissues or organs.In this review,we provide a glance at very diverse topics of auxin biology,such as biosynthesis,conjugation,oxidation,and transport of auxin.This broad,but certainly superficial,overview highlights the mutual importance of auxin metabolism and transport.Moreover,it allows pinpointing how auxin metabolism and transport get integrated to jointly regulate cellular auxin homeostasis.Even though these processes have been so far only separately studied,we assume that the phytohormonal crosstalk integrates and coordinates auxin metabolism and transport.Besides the integrative power of the global hormone signaling,we additionally introduce the hypothetical concept considering auxin transport components as gatekeepers for auxin responses.

  16. Carbonic anhydrase 5 regulates acid-base homeostasis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ruben Postel

    Full Text Available The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5 mutation, collapse of fins (cof, which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.

  17. The role of biological clock in glucose homeostasis 

    Directory of Open Access Journals (Sweden)

    Piotr Chrościcki

    2013-06-01

    Full Text Available The mechanism of the biological clock is based on a rhythmic expression of clock genes and clock-controlled genes. As a result of their transcripto-translational associations, endogenous rhythms in the synthesis of key proteins of various physiological and metabolic processes are created. The major timekeeping mechanism for these rhythms exists in the central nervous system. The master circadian clock, localized in suprachiasmatic nucleus (SCN, regulates multiple metabolic pathways, while feeding behavior and metabolite availability can in turn regulate the circadian clock. It is also suggested that in the brain there is a food entrainable oscillator (FEO or oscillators, resulting in activation of both food anticipatory activity and hormone secretion that control digestion processes. Moreover, most cells and tissues express autonomous clocks. Maintenance of the glucose homeostasis is particularly important for the proper function of the body, as this sugar is the main source of energy for the brain, retina, erythrocytes and skeletal muscles. Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization. Deficiency of orexin action results in narcolepsy and weight gain, whereas glucose and amino acids can affect activity of the orexin cells. Large-scale genetic studies in rodents and humans provide evidence for the involvement of disrupted clock gene expression rhythms in the pathogenesis of obesity and type 2 diabetes. In general, the current lifestyle of the developed modern societies disturbs the action of biological clock. 

  18. LXR regulate cholesterol homeostasis in the proximal mouse epididymis.

    Directory of Open Access Journals (Sweden)

    Jean-Marc A Lobaccaro

    2010-01-01

    Full Text Available Oxysterol nuclear receptors liver x receptors (LXRalpha and LXRbeta regulate lipid homeostasis when cells have to face high amounts of cholesterol and/or fatty acids. Male mice invalidated for both lxr (LXR-/- are infertile by 5 months of age, and become sterile by the age of 9 months. The epididymis was previously shown to be affected by the gene invalidation, a phenotype specifically located in the two proximal segments of this organ. We demonstrate here that cholesteryl esters are accumulated in a specific cell type of the epididymal epithelium, the apical cells, in these two first segments, in LXR-/- male mice. These accumulations are correlated to a decrease in the amount of a specific membrane cholesterol transporter, ATP-binding cassette A1 (ABCA1 in the caput epididymidis of LXR-/- mice. This decrease is due to a transcriptional down-regulation, and we further demonstrate that ABCA1, in the two first segments of the caput epididymidis, is located in the apical cells, and that its accumulation is lost in these cells for LXR-/- male mice as soon as 4 months of age. These data bring new elements in the cholesterol trafficking pathways in the epididymis, and will help a better understanding of the molecular mechanisms occurring in this organ in relation to the sperm cells maturation process.

  19. Isolation of osteocytes from human trabecular bone.

    Science.gov (United States)

    Prideaux, Matthew; Schutz, Christine; Wijenayaka, Asiri R; Findlay, David M; Campbell, David G; Solomon, Lucian B; Atkins, Gerald J

    2016-07-01

    Osteocytes are essential regulators of bone homeostasis. However, they are difficult to study due to their location within the bone mineralised matrix. Although several techniques have been published for the isolation of osteocytes from mouse bone, no such technique has been described for human osteocytes. We have therefore developed a protocol for the isolation of osteocytes from human trabecular bone samples acquired during surgery. The cells were digested from the bone matrix by sequential collagenase and ethylenediaminetetraacetic acid (EDTA) digestions and the cells from later digests displayed characteristic dendritic osteocyte morphology when cultured ex vivo. Furthermore, the cells expressed characteristic osteocyte marker genes, such as E11, dentin matrix protein 1 (DMP1), SOST, matrix extracellular phosphoglycoprotein (MEPE) and phosphate regulating endopeptidase homologue, X-linked (PHEX). In addition, genes associated with osteocyte perilacunar remodelling, including matrix metallopeptidase-13 (MMP13), cathepsin K (CTSK) and carbonic anhydrase 2 (CAR2) were expressed. The cells also responded to parathyroid hormone (PTH) by downregulating SOST mRNA expression and to 1α,25-dihydroxyvitamin D3 (1,25D) by upregulating fibroblast growth factor 23 (FGF23) mRNA expression. Therefore, the cells behave in a similar manner to osteocytes in vivo. These cells represent an important tool in enhancing current knowledge in human osteocyte biology. PMID:27109824

  20. Macrophage Polarization and Bone Formation: A review.

    Science.gov (United States)

    Horwood, Nicole J

    2016-08-01

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

  1. Calcium and bone disorders in pregnancy

    Directory of Open Access Journals (Sweden)

    Shriraam Mahadevan

    2012-01-01

    Full Text Available Significant transplacental calcium transfer occurs during pregnancy, especially during the last trimester, to meet the demands of the rapidly mineralizing fetal skeleton. Similarly, there is an obligate loss of calcium in the breast milk during lactation. Both these result in considerable stress on the bone mineral homeostasis in the mother. The maternal adaptive mechanisms to conserve calcium are different in pregnancy and lactation. During pregnancy, increased intestinal absorption of calcium from the gut mainly due to higher generation of calcitriol (1,25 dihydroxy vitamin D helps in maintaining maternal calcium levels. On the other hand, during lactation, the main compensatory mechanism is skeletal resorption due to increased generation of parathormone related peptide (PTHrP from the breast. Previous studies suggest that in spite of considerable changes in bone mineral metabolism during pregnancy, parity and lactation are not significantly associated with future risk for osteoporosis. However, in India, the situation may not be the same as a significant proportion of pregnancies occur in the early twenties when peak bone mass is not yet achieved. Further, malnutrition, anemia and vitamin D deficiency are commonly encountered in this age group. This may have an impact on future bone health of the mother. It may also probably provide an opportunity for health care providers for prevention. Other metabolic bone diseases like hypoparathyroidism, hyperparathyroidism and pseudohypoparathyroidism are rarely encountered in pregnancy. Their clinical implications and management are also discussed.

  2. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C;

    1993-01-01

    Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found in...... lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  3. Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration.

    Science.gov (United States)

    Tang, Daniel; Tare, Rahul S; Yang, Liang-Yo; Williams, David F; Ou, Keng-Liang; Oreffo, Richard O C

    2016-03-01

    The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself. PMID:26803405

  4. Chondrosarcoma of the bones of the feet.

    Science.gov (United States)

    Patil, Sanjeev; de Silva, M V Chandu; Crossan, Jim; Reid, Robin

    2003-01-01

    Twelve chondrosarcomas of the bones of the feet from 11 patients in the Scottish Bone Tumor Registry were reviewed. One patient with diaphyseal aclasis (osteochondromatosis) developed 2 chondrosarcomas. The mean age of patients was 52.3 years (range, 17 to 83 years). Men were predominantly affected. Four tumors affected the tarsal bones; the rest involved the short tubular bones. The usual clinical presentation was a painful, progressively enlarging swelling. Radiologically, most showed some bone expansion, cortical destruction with indistinct margins, and soft-tissue extension. Histologically, the majority were middle-grade tumors. Treatment included curettage or local excision for 4 tumors and amputation or ray resection for 8 tumors. Follow-up varied from 6 months to 18 years (average, 5.8 years). Local recurrence after surgery was seen in 3 patients. All 3 died because of metastases to the lungs or brain. PMID:14566721

  5. Nasopharyngeal carcinoma with bone marrow metastasis.

    Science.gov (United States)

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  6. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  7. Bone changes in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Alcoholism has been associated with growth impairment,osteomalacia, delayed fracture healing, and asepticnecrosis (primarily necrosis of the femoral head), butthe main alterations observed in the bones of alcoholicpatients are osteoporosis and an increased risk offractures. Decreased bone mass is a hallmark of osteoporosis,and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanolmay affect both mechanisms. It is generally acceptedthat ethanol decreases bone synthesis, and most authorshave reported decreased osteocalcin levels (a "marker" ofbone synthesis), but some controversy exists regardingthe effect of alcohol on bone breakdown, and, indeed,disparate results have been reported for telopeptideand other biochemical markers of bone resorption.In addition to the direct effect of ethanol, systemicalterations such as malnutrition, malabsorption, liverdisease, increased levels of proinflammatory cytokines,alcoholic myopathy and neuropathy, low testosteronelevels, and an increased risk of trauma, play contributoryroles. The treatment of alcoholic bone disease should beaimed towards increasing bone formation and decreasingbone degradation. In this sense, vitamin D and calciumsupplementation, together with biphosphonates areessential, but alcohol abstinence and nutritional improvementare equally important. In this review we study thepathogenesis of bone changes in alcoholic liver diseaseand discuss potential therapies.

  8. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    Directory of Open Access Journals (Sweden)

    Jin Shao

    2015-01-01

    Full Text Available Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG, sclerostin (SOST, and Dickopf (DKK which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN, which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism.

  9. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    OpenAIRE

    Thobe, Megan N.; Rinker-Schaeffer, Carrie W.; Clark, Robert J; Bainer, Russell O.; Prasad, Sandip M.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules ...

  10. Bone microdamage, remodeling and bone fragility: how much damage is too much damage?

    OpenAIRE

    Seref-Ferlengez, Zeynep; Kennedy, Oran D; Schaffler, Mitchell B.

    2015-01-01

    Microdamage resulting from fatigue or ‘wear and tear' loading contributes to bone fragility; however, the full extent of its influence is not completely understood. Linear microcracks (∼50–100 μm) and diffuse damage (clusters of sublamellar-sized cracks) are the two major bone microdamage types, each with different mechanical and biological consequences. Healthy bone, due to its numerous microstructural interfaces and its ability to affect matrix level repair, deals effectively with microdama...

  11. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  12. The effects of bone density and crestal cortical bone thickness on micromotion and peri-implant bone strain distribution in an immediately loaded implant: a nonlinear finite element analysis

    Science.gov (United States)

    2016-01-01

    Purpose This study investigated the effects of bone density and crestal cortical bone thickness at the implant-placement site on micromotion (relative displacement between the implant and bone) and the peri-implant bone strain distribution under immediate-loading conditions. Methods A three-dimensional finite element model of the posterior mandible with an implant was constructed. Various bone parameters were simulated, including low or high cancellous bone density, low or high crestal cortical bone density, and crestal cortical bone thicknesses ranging from 0.5 to 2.5 mm. Delayed- and immediate-loading conditions were simulated. A buccolingual oblique load of 200 N was applied to the top of the abutment. Results The maximum extent of micromotion was approximately 100 μm in the low-density cancellous bone models, whereas it was under 30 μm in the high-density cancellous bone models. Crestal cortical bone thickness significantly affected the maximum micromotion in the low-density cancellous bone models. The minimum principal strain in the peri-implant cortical bone was affected by the density of the crestal cortical bone and cancellous bone to the same degree for both delayed and immediate loading. In the low-density cancellous bone models under immediate loading, the minimum principal strain in the peri-implant cortical bone decreased with an increase in crestal cortical bone thickness. Conclusions Cancellous bone density may be a critical factor for avoiding excessive micromotion in immediately loaded implants. Crestal cortical bone thickness significantly affected the maximum extent of micromotion and peri-implant bone strain in simulations of low-density cancellous bone under immediate loading. PMID:27382504

  13. Calcium homeostasis modulator (CALHM) ion channels.

    Science.gov (United States)

    Ma, Zhongming; Tanis, Jessica E; Taruno, Akiyuki; Foskett, J Kevin

    2016-03-01

    Calcium homeostasis modulator 1 (CALHM1), formerly known as FAM26C, was recently identified as a physiologically important plasma membrane ion channel. CALHM1 and its Caenorhabditis elegans homolog, CLHM-1, are regulated by membrane voltage and extracellular Ca(2+) concentration ([Ca(2+)]o). In the presence of physiological [Ca(2+)]o (∼1.5 mM), CALHM1 and CLHM-1 are closed at resting membrane potentials but can be opened by strong depolarizations. Reducing [Ca(2+)]o increases channel open probability, enabling channel activation at negative membrane potentials. Together, voltage and Ca(2+) o allosterically regulate CALHM channel gating. Through convergent evolution, CALHM has structural features that are reminiscent of connexins and pannexins/innexins/LRRC8 (volume-regulated anion channel (VRAC)) gene families, including four transmembrane helices with cytoplasmic amino and carboxyl termini. A CALHM1 channel is a hexamer of CALHM1 monomers with a functional pore diameter of ∼14 Å. CALHM channels discriminate poorly among cations and anions, with signaling molecules including Ca(2+) and ATP able to permeate through its pore. CALHM1 is expressed in the brain where it plays an important role in cortical neuron excitability induced by low [Ca(2+)]o and in type II taste bud cells in the tongue that sense sweet, bitter, and umami tastes where it functions as an essential ATP release channel to mediate nonsynaptic neurotransmitter release. CLHM-1 is expressed in C. elegans sensory neurons and body wall muscles, and its genetic deletion causes locomotion defects. Thus, CALHM is a voltage- and Ca(2+) o-gated ion channel, permeable to large cations and anions, that plays important roles in physiology. PMID:26603282

  14. Bone marrow biopsy

    Science.gov (United States)

    Biopsy - bone marrow ... A bone marrow biopsy may be done in the health care provider's office or in a hospital. The sample may be taken from the pelvic or breast bone. Sometimes, other areas are used. Marrow is removed ...

  15. Bone marrow aspiration

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003658.htm Bone marrow aspiration To use the sharing features on this page, please enable JavaScript. Bone marrow is the soft tissue inside bones that helps ...

  16. Effects of Spaceflight on Cells of Bone Marrow Origin

    Directory of Open Access Journals (Sweden)

    Engin Özçivici

    2013-03-01

    Full Text Available Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types.

  17. Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis.

    Science.gov (United States)

    Boparai, Ravneet K; Arum, Oge; Khardori, Romesh; Bartke, Andrzej

    2010-10-01

    In contrast to its stimulatory effects on musculature, bone, and organ development, and its lipolytic effects, growth hormone (GH) opposes insulin effects on glucose metabolism. Chronic GH overexposure is thought to result in insulin insensitivity and decreased blood glucose homeostatic control. Yet, despite the importance of this concept for basic biology, as well as human conditions of GH excess or deficiency, no systematic assessment of the impact of GH over- expression on glucose homeostasis and insulin sensitivity has been conducted. We report that male and female adult GH transgenic mice have enhanced glucose tolerance compared to littermate controls and this effect is not dependent on age or on the particular heterologous GH transgene used. Furthermore, increased glucose-stimulated insulin secretion, augmented insulin sensitivity, and muted gluconeogenesis were also observed in bovine GH overexpressing mice. These results show that markedly increased systemic GH concentration in GH-transgenic mice exerts unexpected beneficial effects on glucose homeostasis, presumably via a compensatory increase in insulin release. The counterintuitive nature of these results challenges previously held presumptions of the physiology of these mice and other states of GH overexpression or suppression. In addition, they pose intriguing queries about the relationships between GH, endocrine control of metabolism, and aging. PMID:20707609

  18. Anorexia Nervosa and Bone

    OpenAIRE

    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...

  19. Newly reported roles of thyroid-stimulating hormone and follicle-stimulating hormone in bone remodelling

    OpenAIRE

    Sendak, Rebecca A.; Sampath, T. Kuber; McPherson, John M.

    2007-01-01

    Thyroid-stimulating hormone (TSH) and follicle-stimulating hormone (FSH) have both been recently implicated in bone remodelling. Clinical evidence, as well as data from TSH receptor and thyroid hormone receptor knockout mice, suggest that TSH has a direct effect on skeletal homeostasis, although some data are conflicting. Recently, the exogenous administration of TSH has been shown to positively impact bone in oophrectomised rats. These data, along with their potential implications for the tr...

  20. Biology of the RANKL–RANK–OPG System in Immunity, Bone, and Beyond

    OpenAIRE

    Walsh, Matthew C.; Choi, Yongwon

    2014-01-01

    Discovery and characterization of the cytokine receptor-cytokine-decoy receptor triad formed by receptor activator of nuclear factor kappa-B ligand (RANKL)–receptor activator of NF-κB (RANK)–osteoprotegerin (OPG) have led not only to immense advances in understanding the biology of bone homeostasis, but have also crystalized appreciation of the critical regulatory relationship that exists between bone and immunity, resulting in the emergence of the burgeoning field of osteoimmunology. RANKL–R...

  1. Role of Bone Biopsy in Stages 3 to 4 Chronic Kidney Disease

    OpenAIRE

    Gal-Moscovici, Anca; Sprague, Stuart M.

    2008-01-01

    Secondary hyperparathyroidism develops relatively early in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. The disease state in chronic kidney disease, which includes the histologic features of bone disease, defined as renal osteodystrophy, and the hormonal and biochemical disturbances, have recently been redefined as a disease syndrome and is referred to as “chronic kidney disease–mineral and bone disorder.” As chronic kidney disease progres...

  2. Using glutamate homeostasis as a target for treating addictive disorders

    OpenAIRE

    Reissner, Kathryn J.; Kalivas, Peter W.

    2010-01-01

    Well-developed cellular mechanisms exist to preserve glutamate homeostasis and regulate extrasynaptic glutamate levels. Accumulating evidence indicates that disruptions in glutamate homeostasis are associated with addictive disorders. The disruptions in glutamate concentrations observed following prolonged exposure to drugs of abuse are associated with changes in the function and activity of several key components within the homeostatic control mechanism, including the cystine/glutamate excha...

  3. Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies

    OpenAIRE

    Paolo Bonaldo; Paolo Grumati

    2012-01-01

    Skeletal muscles are the agent of motion and one of the most important tissues responsible for the control of metabolism. The maintenance of muscle homeostasis is finely regulated by the balance between catabolic and anabolic process. Macroautophagy (or autophagy) is a catabolic process that provides the degradation of protein aggregation and damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagy flux is fundamental for the homeostasis o...

  4. Redox homeostasis: The Golden Mean of healthy living

    Directory of Open Access Journals (Sweden)

    Fulvio Ursini

    2016-08-01

    Full Text Available The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles

  5. Redox homeostasis: The Golden Mean of healthy living.

    Science.gov (United States)

    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-08-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  6. Plasticity and Dedifferentiation within the Pancreas: Development, Homeostasis, and Disease

    OpenAIRE

    Puri, Sapna; Folias, Alexandra E.; Hebrok, Matthias

    2014-01-01

    Cellular identity is established by genetic, epigenetic, and environmental factors that regulate organogenesis and tissue homeostasis. Although some flexibility in fate potential is beneficial to overall organ health, dramatic changes in cellular identity can have disastrous consequences. Emerging data within the field of pancreas biology are revising current beliefs about how cellular identity is shaped by developmental and environmental cues under homeostasis and stress conditions. Here, we...

  7. The GARP complex is required for cellular sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Fröhlich, Florian; Petit, Constance; Kory, Nora;

    2015-01-01

    (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation...... the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2....

  8. Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease

    OpenAIRE

    Leeman, Kristen T.; Fillmore, Christine M.; Kim, Carla F.

    2014-01-01

    The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of c...

  9. Sex differences in metabolic homeostasis, diabetes, and obesity

    OpenAIRE

    Mauvais-Jarvis, Franck

    2015-01-01

    There are fundamental aspects of the control of metabolic homeostasis that are regulated differently in males and females. This sex asymmetry represents an evolutionary paradigm for females to resist the loss of energy stores. This perspective discusses the most fundamental sex differences in metabolic homeostasis, diabetes, and obesity. Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puber...

  10. Bone strength: more than just bone density.

    Science.gov (United States)

    Ott, Susan M

    2016-01-01

    The following bone density measurements have limited utility in determining bone strength because they do not include bone quality: microarchitecture, mineralization, ability to repair damage, collagen structure, crystal size, or marrow composition. Patients with kidney disease have poor bone quality. Newman et al. now describe beneficial effects with raloxifene in an animal model of progressive kidney disease. These biomechanical measurements will be important in the development of medications to decrease fractures in patients. PMID:26759040

  11. Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats

    International Nuclear Information System (INIS)

    Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of 137Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with 137Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to 137Cs on Vitamin D3 metabolism, a hormone essential in bone homeostasis. Rats were exposed to 137Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D3 metabolism, related nuclear receptors and Vitamin D3 target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p 137Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D3) plasma level (53%, p = 0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p 137Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of 137Cs affects Vitamin D3 active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders

  12. Sex steroids and bone: current perspectives.

    Science.gov (United States)

    Balasch, Juan

    2003-01-01

    Although the process of bone remodelling or its control has not yet been fully elucidated there is, at present, sufficient information available to conclude that ovarian steroids (estrogens, androgens, progesterone) play an essential role in skeletal homeostasis. The mechanism of action of sex steroids on the skeleton is still not entirely clear, but it has traditionally included indirect effects on systemic hormones that regulate calcium balance and a direct receptor-mediated action. More recently, changes in cytokine production within the bone marrow, as well as pro-apoptotic and anti-apoptotic effects in the osteoblastic cells, have been proposed as new perspectives on the cellular and molecular mechanisms by which sex steroids influence adult bone homeostasis. Mechanical loading, when combined with estrogens or androgens, results in a greater osteogenic response than either condition separately. Women are especially at risk for osteoporosis if they have had a premature or surgical menopause and have not received hormone replacement therapy (HRT). Other reproductive factors that can help to identify women with osteopenia and emphasize the role of sex steroids in preserving bone mass in premenopausal women include: age at menarche, menstrual history and irregularities (including those associated with excessive exercise), age at menopause, previous hysterectomy, hyperprolactinaemia, anorexia nervosa, scoliosis, ovarian dysgenesis, pregnancy and lactation, and pharmacological ovarian suppression. The prevention of osteoporosis starts with the onset of the menarche. A combination of exercise, appropriate nutrition and a healthy lifestyle all maximize bone mineral accrual and result in optimal peak bone mass; normal ovarian function is essential to this process. Unfortunately, many women actually become aware of the need for osteoporosis prevention much later in life, usually after they have already become menopausal. HRT, however, has important limitations for

  13. Bone development

    DEFF Research Database (Denmark)

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

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram...... at 146 days of life and five left and right ribs (fourth to eighth) were removed for analysis. The influence of AKG on skeletal system development was evaluated in relation to both geometrical and mechanical properties, as well as quantitative computed tomography (QCT). No significant differences between...... has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development...

  14. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    Full Text Available We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR, however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25 and sphingolipid biosynthesis (AUR1 and SCS7 genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron

  15. NF-κB in the regulation of epithelial homeostasis and inflammation

    Institute of Scientific and Technical Information of China (English)

    Andy Wullaert; Marion C Bonnet; Manolis Pasparakis

    2011-01-01

    Aging-Associated Diseases(CECAD),University of Cologne,Zülpicher Strasse 47a,50674 Cologne,Germany The IκB kinase/NF-κB signaling pathway has been implicated in the pathogenesis of several inflammatory diseases.Increased activation of NF-κB is often detected in both immune and non-immune cells in tissues affected by chronic inflammation,where it is believed to exert detrimental functions by inducing the expression of proinflammatory mediators that orchestrate and sustain the inflammatory response and cause tissue damage.Thus,increased NF-κB activation is considered an important pathogenic factor in many acute and chronic inflammatory disorders,raising hopes that NF-κB inhibitors could be effective for the treatment of inflammatory diseases.However,ample evidence has accumulated that NF-κB inhibition can also be harmful for the organism,and in some cases trigger the development of inflammation and disease.These findings suggested that NF-κB signaling has important functions for the maintenance of physiological immune homeostasis and for the prevention of inflammatory diseases in many tissues.This beneficial function of NF-κB has been predominantly observed in epithelial cells,indicating that NF-κB signaling has a particularly important role for the maintenance of immune homeostasis in epithelial tissues.It seems therefore that NF-κB displays two faces in chronic inflammation: on the one hand increased and sustained NF-κB activation induces inflammation and tissue damage,but on the other hand inhibition of NF-κB signaling can also disturb immune homeostasis,triggering inflammation and disease.Here,we discuss the mechanisms that control these apparently opposing functions of NF-κB signaling,focusing particularly on the role of NF-κB in the regulation of immune homeostasis and inflammation in the intestine and the skin.

  16. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    Science.gov (United States)

    Hameed, Saif; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Goswami, Shyamal K; Prasad, Rajendra

    2011-01-01

    We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR), however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS) based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25) and sphingolipid biosynthesis (AUR1 and SCS7) genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron deprived Candida

  17. Modelling the role of the Hsp70/Hsp90 system in the maintenance of protein homeostasis.

    Directory of Open Access Journals (Sweden)

    Carole J Proctor

    Full Text Available Neurodegeneration is an age-related disorder which is characterised by the accumulation of aggregated protein and neuronal cell death. There are many different neurodegenerative diseases which are classified according to the specific proteins involved and the regions of the brain which are affected. Despite individual differences, there are common mechanisms at the sub-cellular level leading to loss of protein homeostasis. The two central systems in protein homeostasis are the chaperone system, which promotes correct protein folding, and the cellular proteolytic system, which degrades misfolded or damaged proteins. Since these systems and their interactions are very complex, we use mathematical modelling to aid understanding of the processes involved. The model developed in this study focuses on the role of Hsp70 (IPR00103 and Hsp90 (IPR001404 chaperones in preventing both protein aggregation and cell death. Simulations were performed under three different conditions: no stress; transient stress due to an increase in reactive oxygen species; and high stress due to sustained increases in reactive oxygen species. The model predicts that protein homeostasis can be maintained during short periods of stress. However, under long periods of stress, the chaperone system becomes overwhelmed and the probability of cell death pathways being activated increases. Simulations were also run in which cell death mediated by the JNK (P45983 and p38 (Q16539 pathways was inhibited. The model predicts that inhibiting either or both of these pathways may delay cell death but does not stop the aggregation process and that eventually cells die due to aggregated protein inhibiting proteasomal function. This problem can be overcome if the sequestration of aggregated protein into inclusion bodies is enhanced. This model predicts responses to reactive oxygen species-mediated stress that are consistent with currently available experimental data. The model can be used to

  18. O-GlcNAcase expression is sensitive to changes in O-GlcNAc homeostasis

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    ZHEN eZHANG

    2014-12-01

    Full Text Available O-linked N-acetylglucosamine (O-GlcNAc is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT and O-GlcNAcase (OGA, which add and remove the modification respectively. The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. Disruptions in O-GlcNAc homeostasis are proposed to lead to the development of diseases such as cancer, diabetes, and Alzheimer’s disease. O-GlcNAc homeostasis is correlated with the expression of OGT and OGA. We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. Pretreating cells with protein translation inhibitor cycloheximide (CHX did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D (AMD. Finally, we performed RNA Polymerase II chromatin immunoprecipitation (ChIP at the OGA promoter and found RNA Pol II occupancy at the transcription start site (TSS was lower after prolonged TMG treatment. Together, these data suggest that OGA transcription was sensitive to changes in O-GlcNAc homeostasis and was potentially regulated by O-GlcNAc.

  19. Exercise, lifestyle, and your bones

    Science.gov (United States)

    Osteoporosis - exercise; Low bone density - exercise ... Osteoporosis is a disease that causes bones to become brittle and more likely to fracture (break). With osteoporosis, the bones lose density. Bone density is the amount of bone ...

  20. Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone.

    Directory of Open Access Journals (Sweden)

    Grażyna E Sroga

    Full Text Available Despite our extensive knowledge of insulin-like growth factor 1 (IGF1 action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN contents and mechanical tests (crack initiation and propagation using compact tension specimens. Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN predict propensity of bone to fracture (initiation and propagation independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones.

  1. Eosinophilic granuloma of temporal bone

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    2016-01-01

    Full Text Available Eosinophilic granuloma is an uncommon granulomatous disease which can affect the temporal bone. Also known as Langerhans cell histiocytosis, the lesion is characterized by uncontrolled proliferation of Langerhans cells. Although initially silent, the disease may erode the mastoid cortex, destroy the tegmen, and extend into the cranial vault, as well as erode the semicircular canals or cochlea. These lesions almost always become infected and can be confused with chronic otomastoiditis. Equally important, temporal bone involvement may represent only one manifestation of a multifocal disease. This report describes a case of 40-year-old male with eosinophilic granuloma involving the right temporal bone extending into midbrain region causing focal compression and displacement of part of the temporal lobe.

  2. Magnetic resonance imaging of the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Baur-Melnyk, Andrea (ed.) [Klinikum der Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2013-08-01

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  3. Magnetic resonance imaging of the bone marrow

    International Nuclear Information System (INIS)

    The first book devoted to MRI of the bone marrow. Describes the MRI appearances of normal bone marrows and the full range of bone marrow disorders. Discusses the role of advanced MRI techniques and contrast enhancement. On account of its unrivalled imaging capabilities and sensitivity, magnetic resonance imaging (MRI) is considered the modality of choice for the investigation of physiologic and pathologic processes affecting the bone marrow. This book describes the MRI appearances of both the normal bone marrow, including variants, and the full range of bone marrow disorders. Detailed discussion is devoted to malignancies, including multiple myeloma, lymphoma, chronic myeloproliferative disorders, leukemia, and bone metastases. Among the other conditions covered are benign and malignant compression fractures, osteonecrosis, hemolytic anemia, Gaucher's disease, bone marrow edema syndrome, trauma, and infective and non-infective inflammatory disease. Further chapters address the role of MRI in assessing treatment response, the use of contrast media, and advanced MRI techniques. Magnetic Resonance Imaging of the Bone Marrow represents an ideal reference for both novice and experienced practitioners.

  4. Matrix metalloproteinases in bone marrow: roles of gelatinases in physiological hematopoiesis and hematopoietic malignancies

    OpenAIRE

    Yu, X.F.; Han, Z. C.

    2006-01-01

    Turnover balance of extracellular matrix (ECM) is a prerequisite for the structural and functional homeostasis of bone marrow (BM) microenvironment. The role of ECM in physiologic hematopoiesis and its pathologic change in hematopoietic malignancies are very important and under extensive investigation. Accumulating evidence suggests that matrix metalloproteinases (MMPs), a family of zinc-dependent proteinases, take an active part in the physiological and pa...

  5. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    NARCIS (Netherlands)

    Brisset, Jean-Christophe; Hoff, Benjamin A.; Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galban, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galban, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.; Schakel, Tim

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellul

  6. Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone loss during vitamin D-deficiency.

    Science.gov (United States)

    Lam, Nga N; Triliana, Rahma; Sawyer, Rebecca K; Atkins, Gerald J; Morris, Howard A; O'Loughlin, Peter D; Anderson, Paul H

    2014-10-01

    There are several lines of evidence that demonstrate the ability of 1,25-dihydroxyvitamin D (1,25(OH)2D3), acting via the vitamin D receptor (VDR) to mediate negative or positive effects in bone. Transgenic over-expression of VDR in osteoblasts and osteocytes in a mouse model (OSVDR) has been previously shown to inhibit processes of bone resorption and enhance bone formation, under conditions of adequate calcium intake. While these findings suggest that vitamin D signalling in osteoblasts and osteocytes promotes bone mineral accrual, the vitamin D requirement for this action is not well understood. In this study, 4 week old female OSVDR and wild-type (WT) mice were fed either a vitamin D-replete (1000IU/kg diet, D+) or vitamin D-deficient (D-) diet for 4 months to observe changes to bone mineral homeostasis. Tibial bone mineral volume was analysed by micro-CT and changes to bone cell activities were measured using standard dynamic histomorphometric techniques. While vitamin D-deplete WT mice demonstrated a reduction in periosteal bone accrual and overall bone mineral volume, OSVDR mice, however, displayed increased cortical and cancellous bone volume in mice which remained higher during vitamin D-depletion due to a reduced osteoclast number and increased bone formation rate. These data suggest that increased VDR-mediated activity in osteoblast and osteocytes prevents bone loss due to vitamin D-deficiency. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24434283

  7. Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Gao Shu-guang

    2012-06-01

    Full Text Available Abstract Background Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF. However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Methods Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC, bone mineral density (BMD, bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Results Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption, affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface, and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. Conclusion The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

  8. Effects of obesity on bone metabolism

    Directory of Open Access Journals (Sweden)

    Cao Jay J

    2011-06-01

    Full Text Available Abstract Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely

  9. The Role of GH/IGF-I Axis in Muscle Homeostasis During Weightlessness

    Science.gov (United States)

    Schwartz, Robert J.

    1997-01-01

    Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.

  10. Misregulation of iron homeostasis in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Gajowiak, Anna; Styś, Agnieszka; Starzyński, Rafał R; Staroń, Robert; Lipiński, Paweł

    2016-01-01

    Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS) requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood-cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1) gene. Mutations in the SOD1 gene constitute one of the most common genetic causes of the inherited form of ALS. However, it should be considered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymatic activity, a condition which does not occur in human pathology and which may itself change the expression of iron metabolism genes. PMID:27356602

  11. Chinese herbal compound affects osteoblast proliferation and bone mineral density%中药复方对成骨细胞增殖及骨密度的影响*

    Institute of Scientific and Technical Information of China (English)

    颜军礼; 李蒙; 李瑞玉; 吴立萍; 孙艳浮; 李会龙

    2013-01-01

      背景:复方中药是由多种矿物植物动物等物质组成的复方药物,在治疗骨代谢疾病方面,能通过多途径,多靶点发挥综合治疗作用。  目的:研究复方中药对成骨细胞增殖及骨密度的影响,探讨复方中药对骨质疏松症的药理作用。  方法:回顾性分析以往经实验研究证实的某些复方中药对骨质疏松症动物模型成骨细胞增殖分化及骨密度的影响,分析影响复方中药促进骨形成的因素,通过对成骨细胞体外培养方法进行筛选,找出促进细胞增殖分化、提高骨密度的药物适宜剂量,与化学药物结果进行对照研究。  结果与结论:复方中药能够促进成骨细胞增殖分化、提高骨密度,在治疗骨质疏松症方面具有标本兼治、毒副作用小等优点,但复方中药在改善骨密度水平方面不及化学药物,并且应通过长期、大样本的临床研究,降低骨质疏松性骨折风险的干预作用。%BACKGROUND:Compound Chinese medicine is a kind of compound drugs with the combination of minerals, plants and animals, which play the multi-target integrated treatment effects in the treatment of bone metabolic disease through various methods. OBJECTIVE:To research the effect of compound traditional Chinese medicine on the proliferation and bone mineral density of osteoblasts, and to explore the pharmacological effect of compound traditional Chinese medicine in the treatment of osteoporosis. METHODS: A retrospective analysis was performed to analyze the effect of some compound traditional Chinese medicines on the proliferation and bone mineral density of osteoblasts that identified in the previous studies, in order to analyze the factors of compound traditional Chinese medicines that can promote the bone formation. The appropriate dose of the drugs that can promote cel proliferation and differentiation and improve the bone mineral density was screened out

  12. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

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

  13. Bone scan in rheumatology

    International Nuclear Information System (INIS)

    In this chapter a revision is made concerning different uses of bone scan in rheumatic diseases. These include reflex sympathetic dystrophy, osteomyelitis, spondyloarthropaties, metabolic bone diseases, avascular bone necrosis and bone injuries due to sports. There is as well some comments concerning pediatric pathology and orthopedics. (authors). 19 refs., 9 figs

  14. Bone Marrow Diseases

    Science.gov (United States)

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

  15. Bone Marrow Transplantation

    Science.gov (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a ...

  16. Bone grafts in dentistry

    OpenAIRE

    Prasanna Kumar; Belliappa Vinitha; Ghousia Fathima

    2013-01-01

    Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

  17. Bone grafts in dentistry

    Directory of Open Access Journals (Sweden)

    Prasanna Kumar

    2013-01-01

    Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

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

    OpenAIRE

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

    2010-01-01

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

  19. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Science.gov (United States)

    Brisset, Jean-Christophe; Hoff, Benjamin A; Chenevert, Thomas L; Jacobson, Jon A; Boes, Jennifer L; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D; Pienta, Kenneth J; Galbán, Craig J; Meyer, Charles R; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S; Hussain, Maha; Ross, Brian D

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (pprostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. PMID:25859981

  20. A comparative study of calcium sulfate artificial bone graft versus allograft in the reconstruction of bone defect after tumor curettage

    Institute of Scientific and Technical Information of China (English)

    Yang Yongkun; Niu Xiaohui; Zhang Qing; Hao Lin; Ding Yi; Xu Hairong

    2014-01-01

    Background Cavity reconstruction after benign bone tumor removal is varied and controversial.AIIograft is widely used but is associated with complications.New bone substitutes,such as calcium sulfate artificial bone,have been introduced for bone tumor operation.However,the bone healing response of artificial bone has not been compared with allograft bone.We therefore compared calcium sulfate grafts (study group) with bone allografts (control group) for the treatment of benign bone tumors.Methods We retrospectively reviewed 50 patients who underwent calcium sulfate reconstruction and 50 patients who underwent allograft cancellous bone reconstruction.The two groups were well matched.The mean follow-up time of the study group was 19.9 (12-55) months.We investigated bone healing response,complications,and factors affecting bone healing.Results At the last follow-up,84% (42/50) of cases in the study group and 62% (31/50) of cases in the control group had achieved clinical healing (P=0.013).The initial healing rate showed no significant difference between the two groups (100% vs.96%,P=0.153).The mean healing times for calcium sulfate and allograft bone were 9.6 (3-42) months and 13.8 (3-36) months,respectively (P <0.01).Complications in the study group were minor and resolved.Implant volume was a significant factor affecting bone healing.Conclusion The calcium sulfate bone substitute showed a satisfactory healing outcome and safety profile in reconstruction of bone defects after benign bone tumor curettage,especially in smaller cavities.

  1. Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus

    DEFF Research Database (Denmark)

    Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa; Saito, Hiroaki; Yin, Min; Green, Thomas A; Lotinun, Sutada; Kveiborg, Marie; Horne, William C; Nestler, Eric J; Baron, Roland

    2012-01-01

    The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention due to its potential relevance to osteoporosis, obesity and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the......-antagonistic properties, have increased energy expenditure and bone mass. Since these mice express ¿FosB in bone, fat and hypothalamus, we sought to determine 1) whether overexpression of ¿FosB within the hypothalamus was sufficient to regulate energy expenditure and whether it would also regulate bone mass, and 2......) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ¿FosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass...

  2. Relationship between nanoscale mineral properties and calcein labeling in mineralizing bone surfaces.

    Science.gov (United States)

    Aido, Marta; Kerschnitzki, Michael; Hoerth, Rebecca; Burghammer, Manfred; Montero, Cédric; Checa, Sara; Fratzl, Peter; Duda, Georg N; Willie, Bettina M; Wagermaier, Wolfgang

    2014-08-01

    Bone's mineral properties, such as particle thickness and degree of alignment have been associated with bone quality. Bone formation, remodeling, aging of the tissue and mineral homeostasis influence mineral particle properties leading to specific patterns across bone. Scanning small angle X-ray scattering (sSAXS) with synchrotron radiation is a powerful tool, which allows us to study bone's nanoscale mineral properties in a position-resolved way. We used sSAXS, fluorescence light microscopy and backscattered electron (BSE) imaging to study bone's mineral properties at the tibial midshaft of in vivo-loaded mice. By combining these techniques, we could detect local changes in mineral properties. Regions labeled with calcein fluorochrome have lower mean mineral thickness and degree of mineral alignment. We also observed thinner and less aligned mineral particles near blood vessels. We conclude that mineral properties (i) are altered by fluorochrome labeling and (ii) depend on the proximity to blood vessels. PMID:25158172

  3. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility.

    Directory of Open Access Journals (Sweden)

    Lamya Karim

    Full Text Available Non-enzymatic glycation (NEG and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC. Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks. The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage.

  4. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility.

    Science.gov (United States)

    Karim, Lamya; Vashishth, Deepak

    2012-01-01

    Non-enzymatic glycation (NEG) and enzymatic biochemical processes create crosslinks that modify the extracellular matrix (ECM) and affect the turnover of bone tissue. Because NEG affects turnover and turnover at the local level affects microarchitecture and formation and removal of microdamage, we hypothesized that NEG in cancellous bone is heterogeneous and accounts partly for the contribution of microarchitecture and microdamage on bone fragility. Human trabecular bone cores from 23 donors were subjected to compression tests. Mechanically tested cores as well as an additional 19 cores were stained with lead-uranyl acetate and imaged to determine microarchitecture and measure microdamage. Post-yield mechanical properties were measured and damaged trabeculae were extracted from a subset of specimens and characterized for the morphology of induced microdamage. Tested specimens and extracted trabeculae were quantified for enzymatic and non-enzymatic crosslink content using a colorimetric assay and Ultra-high Performance Liquid Chromatography (UPLC). Results show that an increase in enzymatic crosslinks was beneficial for bone where they were associated with increased toughness and decreased microdamage. Conversely, bone with increased NEG required less strain to reach failure and were less tough. NEG heterogeneously modified trabecular microarchitecture where high amounts of NEG crosslinks were found in trabecular rods and with the mechanically deleterious form of microdamage (linear microcracks). The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage. PMID:22514706

  5. Bone Marrow Cell Transfer into Fetal Circulation Can Ameliorate Genetic Skin Diseases by Providing Fibroblasts to the Skin and Inducing Immune Tolerance

    OpenAIRE

    Chino, Takenao; Tamai, Katsuto; Yamazaki, Takehiko; Otsuru, Satoru; Kikuchi, Yasushi; Nimura, Keisuke; Endo, Masayuki; Nagai, Miki; Uitto, Jouni; Kitajima, Yasuo; Kaneda, Yasufumi

    2008-01-01

    Recent studies have shown that skin injury recruits bone marrow-derived fibroblasts (BMDFs) to the site of injury to accelerate tissue repair. However, whether uninjured skin can recruit BMDFs to maintain skin homeostasis remains uncertain. Here, we investigated the appearance of BMDFs in normal mouse skin after embryonic bone marrow cell transplantation (E-BMT) with green fluorescent protein-transgenic bone marrow cells (GFP-BMCs) via the vitelline vein, which traverses the uterine wall and ...

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

    OpenAIRE

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

    2013-01-01

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

  7. The controversy of cranial bone motion.

    Science.gov (United States)

    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. PMID:9243408

  8. PPARα: A Master Regulator of Bilirubin Homeostasis

    OpenAIRE

    Cyril Bigo; Jenny Kaeding; Diala El Husseini; Iwona Rudkowska; Mélanie Verreault; Marie Claude Vohl; Olivier Barbier

    2014-01-01

    Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR) α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC) and coronary artery smooth muscle cells (CASMC) were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin...

  9. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    International Nuclear Information System (INIS)

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

  10. Anorexia nervosa and bone.

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2014-06-01

    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 additional concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, and 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, physiological 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

  11. Anorexia Nervosa and Bone

    Science.gov (United States)

    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

  12. Impact of estradiol, ER subtype specific agonists and genistein on energy homeostasis in a rat model of nutrition induced obesity.

    Science.gov (United States)

    Weigt, Carmen; Hertrampf, Torsten; Zoth, Nora; Fritzemeier, Karl Heinrich; Diel, Patrick

    2012-04-01

    Estrogens are known to be involved in the control of energy homeostasis. Here we investigated the role of ER alpha and ER beta in a model of nutrition induced obesity. Ovariectomized Wistar rats were fed a high fat diet and received either vehicle, E2, ER subtype selective agonists (Alpha and Beta) or genistein. After 10 weeks, body weight, visceral fat, serum leptin, blood lipids, and in the soleus muscle anabolic markers were determined. Treatment with E2 and Alpha decreased body weight, total cholesterol and VLDL. Visceral fat mass, adipocyte size, and serum leptin were reduced by E2, Alpha and Beta. In the soleus muscle, treatment with E2 and Beta modulated Igf1 and Pax7 gene expression and resulted in larger muscle fibers. Our data indicate that blood lipids are affected via ER alpha, whereas activation of ER beta results in an increase of soleus muscle mass. Adipose tissue homeostasis seems to be affected via both ERs. PMID:22230815

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

    Science.gov (United States)

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

    2013-12-01

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

  14. Bone Adaptation and Regeneration - New Developments

    Science.gov (United States)

    Klein-Nulend, Jenneke; Bacabac, Rommel Gaud

    osteocytes sensing different canalicular flow patterns around cutting cone and reversal zone during loading, thus determining the bone's structure. Disturbances in architecture and permeability of the 3D porous network will affect transduction of mechanical loads to the mechanosensors. Uncovering the cellular and mechanical basis of the osteocyte's response to loading represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. In view of the importance of mechanical stress for maintaining bone strength, mechanical stimuli have great potential for providing a therapeutic approach for bone (re)generation.

  15. Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

    Directory of Open Access Journals (Sweden)

    Ling Binbing

    2012-07-01

    Full Text Available Abstract Background The conditionally essential nutrient, L-carnitine, plays a critical role in a number of physiological processes vital to normal neonatal growth and development. We conducted a systematic evaluation of the developmental changes in key L-carnitine homeostasis mechanisms in the postnatal rat to better understand the interrelationship between these pathways and their correlation to ontogenic changes in L-carnitine levels during postnatal development. Methods mRNA expression of heart, kidney and intestinal L-carnitine transporters, liver γ-butyrobetaine hydroxylase (Bbh and trimethyllysine hydroxylase (Tmlh, and heart carnitine palmitoyltransferase (Cpt were measured using quantitative RT-PCR. L-Carnitine levels were determined by HPLC-UV. Cpt and Bbh activity were measured by a spectrophotometric method and HPLC, respectively. Results Serum and heart L-carnitine levels increased with postnatal development. Increases in serum L-carnitine correlated significantly with postnatal increases in renal organic cation/carnitine transporter 2 (Octn2 expression, and was further matched by postnatal increases in intestinal Octn1 expression and hepatic γ-Bbh activity. Postnatal increases in heart L-carnitine levels were significantly correlated to postnatal increases in heart Octn2 expression. Although cardiac high energy phosphate substrate levels remained constant through postnatal development, creatine showed developmental increases with advancing neonatal age. mRNA levels of Cpt1b and Cpt2 significantly increased at postnatal day 20, which was not accompanied by a similar increase in activity. Conclusions Several L-carnitine homeostasis pathways underwent significant ontogenesis during postnatal development in the rat. This information will facilitate future studies on factors affecting the developmental maturation of L-carnitine homeostasis mechanisms and how such factors might affect growth and development.

  16. Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2012-07-01

    Full Text Available Skeletal muscles are the agent of motion and one of the most important tissues responsible for the control of metabolism. The maintenance of muscle homeostasis is finely regulated by the balance between catabolic and anabolic process. Macroautophagy (or autophagy is a catabolic process that provides the degradation of protein aggregation and damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagy flux is fundamental for the homeostasis of skeletal muscles during physiological situations and in response to stress. Defective as well as excessive autophagy is harmful for muscle health and has a pathogenic role in several forms of muscle diseases. This review will focus on the role of autophagy in muscle homeostasis and diseases.

  17. Bioelectrical homeostasis as a component of acupuncture mechanism.

    Science.gov (United States)

    Zukauskas, G; Dapsys, K

    1991-01-01

    Low frequency electrical current and super-high frequency electromagnetic field were applied to acupuncture points of stomach meridian in dogs. The stimulation effect on Bioelectrical potentials of 5 acupuncture points of stomach, spleen, liver, kidney, small intestine meridians and non-acupuncture skin zones was studied in conditions of blocked autonomic ganglia or neuro-muscular junctions of the dog. The influence of ganglioblockading and myorelaxating drugs on Bioelectrical potentials of acupuncture points was also researched. The results are discussed from the neurohumoural and bioelectrical hypotheses points of view. The conclusion that both mechanisms of acupuncture supplement each other is drawn. The principle of bioelectrical homeostasis as a component of acupuncture mechanism is proposed. Bioelectrical homeostasis along with other kinds of homeostasis forms a system of first level homeostats which is united into second level homeostat by the autonomic nervous system. PMID:1685620

  18. Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB’WHU Chronically Infected Chinese Rhesus Macaque

    OpenAIRE

    Zhang, Gao-Hong; Wu, Run-Dong; Zheng, Hong-Yi; Zhang, Xiao-Liang; Zhang, Ming-Xu; Tian, Ren-Rong; Liu, Guang-Ming; Pang, Wei; Zheng, Yong-Tang

    2015-01-01

    Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB'WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study....

  19. Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB'WHU Chronically Infected Chinese Rhesus Macaque

    OpenAIRE

    Gao-Hong Zhang; Run-Dong Wu; Hong-Yi Zheng; Xiao-Liang Zhang; Ming-Xu Zhang; Ren-Rong Tian; Guang-Ming Liu; Wei Pang; Yong-Tang Zheng

    2015-01-01

    Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB’WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study....

  20. Combinatory effects of siRNA‐induced myostatin inhibition and exercise on skeletal muscle homeostasis and body composition

    OpenAIRE

    Mosler, Stephanie; Relizani, Karima,; Mouisel, Etienne; Amthor, Helge; Diel, Patrick

    2014-01-01

    Abstract Inhibition of myostatin (Mstn) stimulates skeletal muscle growth, reduces body fat, and induces a number of metabolic changes. However, it remains unexplored how exercise training modulates the response to Mstn inhibition. The aim of this study was to investigate how siRNA‐mediated Mstn inhibition alone but also in combination with physical activity affects body composition and skeletal muscle homeostasis. Adult mice were treated with Mstn‐targeting siRNA and subjected to a treadmill...

  1. Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo.

    Science.gov (United States)

    Holen, I; Walker, M; Nutter, F; Fowles, A; Evans, C A; Eaton, C L; Ottewell, P D

    2016-03-01

    Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, post-menopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER+ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth. ER+ve (MCF7, T47D) or ER-ve (MDA-MB-231) cells were administered by inter-mammary or inter-cardiac injection into female nude mice ± estradiol. Mice were administered saline or 100 μg/kg ZOL weekly. Tumour growth, dissemination of tumour cells in blood, bone and bone turnover were monitored by luciferase imaging, histology, flow cytometry, two-photon microscopy, micro-CT and TRAP/P1NP ELISA. Estradiol induced metastasis of ER+ve cells to bone in 80-100 % of animals whereas bone metastases from ER-ve cells were unaffected. Administration of ZOL had no effect on tumour growth in the fat pad but significantly inhibited dissemination of ER+ve tumour cells to bone and frequency of bone metastasis. Estradiol and ZOL increased bone volume via different mechanisms: Estradiol increased activity of bone forming osteoblasts whereas administration of ZOL to estradiol supplemented mice decreased osteoclast activity and returned osteoblast activity to levels comparable to that of saline treated mice. ER-ve cells require increased osteoclast activity to grow in bone whereas ER+ve cells do not. Zol does not affect ER+ve tumour growth in soft tissue, however, inhibition of bone turnover by ZOL reduced dissemination and growth of ER+ve breast cancer cells in bone. PMID:26585891

  2. The utility of bone scans in rheumatology

    International Nuclear Information System (INIS)

    Full text: Introduction: Bone scans are the commonest diagnostic imaging services requested by Australian rheumatologists. Medicare figures suggest that an average rheumatologist orders about $50 000 (AUS) of bone scans annually. Aims: To ascertain the reasons why rheumatologists request bone scans and how it affects their patient management. Methods: A two-part prospective survey was administered before and after every bone scan ordered by four rheumatologists over a six-month period in 1996. Results: A total of 136 bone scans were requested (66.2% whole body; 33.8% regional; 6% SPECT). The primary indications for scanning were (1) to confirm a clinical diagnosis (38%); (2) to exclude a diagnosis (34%); (3) to localize site of pain (17%); and (4) to assist in management (6%). The common diseases that rheumatologists were attempting to confirm/exclude with bone scanning were inflammatory arthritis, malignancy, and fracture. However, the commonest provisional and final diagnosis was soft tissue rheumatism (18%) followed by inflammatory arthritis (15%) and osteoarthritis (11%). In 24% of patients with a provisional diagnosis of soft tissue rheumatism the diagnosis was changed by the bone scan. The scan was successful in excluding a diagnosis in 88 per cent where this was the primary indication for the test. It was successful in confirming a diagnosis in 79 per cent where this was the primary indication. In 32 per cent the bone scan altered the clinical diagnosis and in 43 per cent it altered management. The bone scan result prevented further investigations in 60 per cent. Conclusions: The commonest pre-scan and post-scan diagnosis is soft tissue rheumatism. Rheumatologists predominantly request bone scanning to confirm or exclude their clinical suspicion of inflammatory arthritis, malignancy, and fracture. Bone scans were successful in achieving these objectives in at least 79 per cent of cases

  3. Artificial Gravity: Effects on Bone Turnover

    Science.gov (United States)

    Heer, M.; Zwart, S /R.; Baecker, N.; Smith, S. M.

    2007-01-01

    The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

  4. Bone-density changes after stroke.

    Science.gov (United States)

    Beaupre, Gary S; Lew, Henry L

    2006-05-01

    It has been many years since bone loss and fracture risk were first recognized as serious complications of stroke. Hip fracture is associated with a substantial increase in morbidity and mortality for stroke survivors, and therefore, assessing and maintaining skeletal health after stroke should be an important clinical goal. Recent long-term, prospective studies have illustrated a highly nonuniform pattern of bone changes after stroke. In general, there is significant bone loss on the paretic side, which is greatest in those patients with the most severe functional deficits. In some patients, bone loss in the paretic arm during the first year after stroke is the equivalent of >20 yrs of bone loss in healthy individuals of comparable age. Bone density in the nonparetic upper limb can actually increase after stroke, consistent with an increase in habitual use of the nonparetic hand. Bone density in the paretic lower limb can decrease by >10% in 12 mos poststroke are needed to determine how long excess bone loss continues after stroke. Studies with more subjects and with more varied disability levels are needed to better understand the relationships between functional deficits and bone loss. New metrics are needed to quantify the intensity and duration of physical activity in the upper and lower limbs that are consistent with previous research on the role of mechanical stimuli in bone adaptation. Finally, an assessment of skeletal health and the factors that affect bone quantity and quality should be a standard component in the clinical management of all survivors of stroke. PMID:16628156

  5. [Microdestruction of the bone].

    Science.gov (United States)

    Iankovskiĭ, V É

    2014-01-01

    The objective of the present study was the detection of microcracks in the compact bone tissue surrounding the fracture and in deformed bone undergoing subcritical loading. The portions of deformed bone tissue and terminal fragments of broken bones were obtained in the form of blocks longitudinally sawcut from the regions of primary and secondary bone rupture. A total of 300 such blocks were available for the examination. All portions of the deformed bone tissue and terminal fragments of broken bones showed up microcracks commensurate with the bone structures. They were actually hardened traces of deformation that preceded the fracture and reflected the volume of the destroyed bone tissue; moreover, in certain cases they allowed to identify the kind of the object that exerted the external action (either a blow or slow bending). PMID:25269164

  6. Transient bone marrow oedema of the foot

    OpenAIRE

    Radke, S.; Vispo-Seara, J.; Walther, M; Ettl, V; Eulert, J

    2001-01-01

    We treated ten patients who on the basis of MRI were suspected to have transient bone marrow oedema. In eight cases the talus was affected, in one the cuboid and in one the navicular bone. All patients had acute onset pain at the ankle. Four were treated with core decompression and had an immediate pain relief. Six were treated conservatively and became also pain-free but with considerable delay.

  7. RARE PRESENTATION OF MELORHEOSTEOSIS INVOLVING CARPAL BONES

    OpenAIRE

    Ramana; Srinivas,; Reddy; Harshad; Guruvardhan

    2014-01-01

    Melorheostosis is a rare sclerosing bone dysplasia, known as Leri disease characterized by a “flowing” hyperostosis of the cortex. Classically, melorheostosis affects the long bones of the skeleton, especially those in the lower extremities . Involvement of wrist is rare. The radiographic appearance has been likened to “dripping wax down the side of a candle.” The clinical and the radiographic manifestations of melorheostosis have been encountered in a 12 - year ...

  8. PPARα: A Master Regulator of Bilirubin Homeostasis

    Directory of Open Access Journals (Sweden)

    Cyril Bigo

    2014-01-01

    Full Text Available Hypolipidemic fibrates activate the peroxisome proliferator-activated receptor (PPAR α to modulate lipid oxidation and metabolism. The present study aimed at evaluating how 3 PPARα agonists, namely, fenofibrate, gemfibrozil, and Wy14,643, affect bilirubin synthesis and metabolism. Human umbilical vein epithelial cells (HUVEC and coronary artery smooth muscle cells (CASMC were cultured in the absence or presence of the 3 activators, and mRNA, protein, and/or activity levels of the bilirubin synthesizing heme oxygenase- (HO- 1 and biliverdin reductase (BVR enzymes were determined. Human hepatocytes (HH and HepG2 cells sustained similar treatments, except that the expression of the bilirubin conjugating UDP-glucuronosyltransferase (UGT 1A1 enzyme and multidrug resistance-associated protein (MRP 2 transporter was analyzed. In HUVECs, gemfibrozil, fenofibrate, and Wy14,643 upregulated HO-1 mRNA expression without affecting BVR. Wy14,643 and fenofibrate also caused HO-1 protein accumulation, while gemfibrozil and fenofibrate favored the secretion of bilirubin in cell media. Similar positive regulations were also observed with the 3 PPARα ligands in CASMCs where HO-1 mRNA and protein levels were increased. In HH and HepG2 cells, both UGT1A1 and MRP2 transcripts were also accumulating. These observations indicate that PPARα ligands activate bilirubin synthesis in vascular cells and metabolism in liver cells. The clinical implications of these regulatory events are discussed.

  9. Glutathione and Transition-Metal Homeostasis in Escherichia coli▿

    OpenAIRE

    Helbig, Kerstin; Bleuel, Corinna; Krauss, Gerd J.; Nies, Dietrich H.

    2008-01-01

    Glutathione (GSH) and its derivative phytochelatin are important binding factors in transition-metal homeostasis in many eukaryotes. Here, we demonstrate that GSH is also involved in chromate, Zn(II), Cd(II), and Cu(II) homeostasis and resistance in Escherichia coli. While the loss of the ability to synthesize GSH influenced metal tolerance in wild-type cells only slightly, GSH was important for residual metal resistance in cells without metal efflux systems. In mutant cells without the P-typ...

  10. The Relationship Between Lower Limb Bone and Muscle in Military Recruits, Response to Physical Training, and Influence of Smoking Status

    OpenAIRE

    Puthucheary, Z; Kordi, M.; Rawal, J.; Eleftheriou, K I; Payne, J.; Montgomery, H. E.

    2015-01-01

    The relationship between bone and skeletal muscle mass may be affected by physical training. No studies have prospectively examined the bone and skeletal muscle responses to a short controlled exercise-training programme. We hypothesised that a short exercise-training period would affect muscle and bone mass together. Methods: Femoral bone and Rectus femoris Volumes (RFVOL) were determined by magnetic resonance imaging in 215 healthy army recruits, and bone mineral density (BMD) by Dual X-Ray...

  11. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  12. PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

    Directory of Open Access Journals (Sweden)

    Dan Cheng

    Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

  13. Serum PBDE levels in exposed rats in relation to effects on thyroxine homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Darnerud, P.O.; Aune, M.; Larsson, L.; Hallgren, S. [National Food Administration, Uppsala (Sweden)

    2004-09-15

    Brominated flame retardants (BFRs) is a group of environmental chemicals for which lately both interest and knowledge have increased considerably. Among the BFRs, the polybrominated diphenyl ethers (PBDEs) have attained special interest. Much data on environmental and human levels have been presented and several toxicological reviews are now published. Among interesting results is the difference in human PBDE levels that seem to exist between U.S.A. and Europe, results that suggest differences in exposure but without being able to pin-point the exact sources. In experimental studies PBDEs alter serum thyroxin levels, an effect seen both in rats and in mice. The mechanism(s) are still not completely clarified, but are thought to include alterations in serum transport, induced enzymatic degradation and possibly also direct effects on the thyroid gland. As perinatal alterations in thyroid homeostasis could affect brain development, early effects on thyroid hormones may be of special concern. Indeed, PBDEs have been shown to affect behaviour and learning in mice, when given neonatally. The aim of the present study was to relate the serum levels of PBDEs in rats to effects of these compounds on thyroxine homeostasis in these animals. Specifically, the relation between serum PBDE levels and effects on serum thyroxine levels was investigated, after two weeks of daily oral exposure. The result may have consequences for the future risk assessment activities on PBDE and specifically in finding the critical serum PBDE concentration at which the effect on thyroid hormone levels begin to occur.

  14. Measurement of Ca/sup 2 +/ effluxes from bone

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, W.F.; Brommage, R.; Myers, C.R.

    1977-01-01

    To facilitate the study of membrane function in the control of the flow of ions into and out of bone, it was desirable to develop a system for the direct quantitation of unidirectional effluxes of calcium and phosphate from bones. Based on a mathematical analysis of the problem, a specially designed Ussing chamber was developed which proved successful. Calvaria from 2-day-old rat pups, 3-day chicks and adult mice were evaluated. Calcium influxes which exceeded the corresponding effluxes were observed in the neonatal calvaria but not with those from adult mice. Also, an asymmetry in efflux was observed in rat calvaria, the inner side of the skull showed a higher efflux than did the external side. No such asymmetry was seen with calvaria from chicks or mice. This new technology should permit a further exploration of the role of the bone membrane in electrolyte homeostasis.

  15. Horizontal alveolar bone loss: A periodontal orphan

    Directory of Open Access Journals (Sweden)

    Jayakumar A

    2010-01-01

    Full Text Available Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician′s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs (of patients diagnosed with chronic periodontitis and seeking periodontal care, which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36% OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2% teeth, and vertical defects were found only in 264 (7.8% of the teeth, which was statistically significant (P<.001. Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3% have addressed vertical bone loss, and 18 (3.7% have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment

  16. Infant dietary patterns and bone mass in childhood: the Generation R Study

    OpenAIRE

    van den Hooven, E. H.; Heppe, D. H. M.; Kiefte-de Jong, J.C.; Medina-Gomez, C; Moll, H.A.; Hofman, A.; Jaddoe, V. W. V.; Rivadeneira, F.; Franco, O. H.

    2015-01-01

    Summary Early life nutrition affects peak bone mass attainment. In this prospective cohort study, children with high adherence to a “dairy and whole grains” pattern in infancy had higher bone mineral density at the age of 6 years. Although the observed effects are small, our study provides insight into mechanisms linking early nutrition to bone acquisition in childhood. Introduction Nutrition in early life may affect peak bone mass attainment. Previous studies on childhood nutrition and skele...

  17. Bone marrow (stem cell) donation

    Science.gov (United States)

    ... lymphoma , and myeloma can be treated with a bone marrow transplant . This is now often called a stem cell ... are two types of bone marrow donation: Autologous bone marrow transplant is when people donate their own bone marrow. " ...

  18. The effect of altitude hypoxia on glucose homeostasis in men

    DEFF Research Database (Denmark)

    Larsen, J J; Hansen, J M; Olsen, Niels Vidiendal;

    1997-01-01

    1. Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia...

  19. Calcium and phosphate homeostasis: concerted interplay of new regulators.

    NARCIS (Netherlands)

    Renkema, K.Y.R.; Alexander, R.T.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2008-01-01

    Calcium (Ca(2+)) and phosphate (P(i)) are essential to many vital physiological processes. Consequently the maintenance of Ca(2+) and P(i) homeostasis is essential to a healthy existence. This occurs through the concerted action of intestinal, renal, and skeletal regulatory mechanisms. Ca(2+) and P(

  20. nfluence of antidepressants on glucose homeostasis : effects and mechanisms

    NARCIS (Netherlands)

    Derijks, H.J.

    2009-01-01

    Depression has shown to be a common morbidity in patients with diabetes mellitus and comorbid depression in diabetes mellitus patients is frequently treated with antidepressants. It has been postulated that antidepressants may interfere with glucose homeostasis and that the interference of antidepre

  1. Renal renin secretion as regulator of body fluid homeostasis

    DEFF Research Database (Denmark)

    Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane;

    2013-01-01

    The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

  2. Activating transcription factor 3 regulates immune and metabolic homeostasis

    Czech Academy of Sciences Publication Activity Database

    Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

    2012-01-01

    Roč. 32, č. 19 (2012), s. 3949-3962. ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

  3. A lysosome-centered view of nutrient homeostasis.

    Science.gov (United States)

    Mony, Vinod K; Benjamin, Shawna; O'Rourke, Eyleen J

    2016-04-01

    Lysosomes are highly acidic cellular organelles traditionally viewed as sacs of enzymes involved in digesting extracellular or intracellular macromolecules for the regeneration of basic building blocks, cellular housekeeping, or pathogen degradation. Bound by a single lipid bilayer, lysosomes receive their substrates by fusing with endosomes or autophagosomes, or through specialized translocation mechanisms such as chaperone-mediated autophagy or microautophagy. Lysosomes degrade their substrates using up to 60 different soluble hydrolases and release their products either to the cytosol through poorly defined exporting and efflux mechanisms or to the extracellular space by fusing with the plasma membrane. However, it is becoming evident that the role of the lysosome in nutrient homeostasis goes beyond the disposal of waste or the recycling of building blocks. The lysosome is emerging as a signaling hub that can integrate and relay external and internal nutritional information to promote cellular and organismal homeostasis, as well as a major contributor to the processing of energy-dense molecules like glycogen and triglycerides. Here we describe the current knowledge of the nutrient signaling pathways governing lysosomal function, the role of the lysosome in nutrient mobilization, and how lysosomes signal other organelles, distant tissues, and even themselves to ensure energy homeostasis in spite of fluctuations in energy intake. At the same time, we highlight the value of genomics approaches to the past and future discoveries of how the lysosome simultaneously executes and controls cellular homeostasis. PMID:27050453

  4. The role of CDX2 in intestinal homeostasis and inflammation

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen

    2011-01-01

    , including luminal bacteria. The Caudal-related homeobox transcription factor 2 (CDX2) is critical in early intestinal differentiation and has been implicated as a master regulator of the intestinal homeostasis and permeability in adults. When expressed, CDX2 modulates a diverse set of processes including...

  5. 7-Rhamnosylated Flavonols Modulate Homeostasis of the Plant Hormone Auxin and Affect Plant Development

    Czech Academy of Sciences Publication Activity Database

    Kuhn, B.M.; Errafi, S.; Bucher, R.; Dobrev, Petre; Geisler, M.; Bigler, L.; Zažímalová, Eva; Ringli, Ch.

    2016-01-01

    Roč. 291, č. 10 (2016), s. 5385-5395. ISSN 0021-9258 R&D Projects: GA ČR(CZ) GAP305/11/0797 Institutional support: RVO:61389030 Keywords : Arabidopsis thaliana * auxin * flavonoid Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.573, year: 2014

  6. Fumonisins affect the intestinal microbial homeostasis in broiler chickens, predisposing to necrotic enteritis.

    Science.gov (United States)

    Antonissen, Gunther; Croubels, Siska; Pasmans, Frank; Ducatelle, Richard; Eeckhaut, Venessa; Devreese, Mathias; Verlinden, Marc; Haesebrouck, Freddy; Eeckhout, Mia; De Saeger, Sarah; Antlinger, Birgit; Novak, Barbara; Martel, An; Van Immerseel, Filip

    2015-01-01

    Fumonisins (FBs) are mycotoxins produced by Fusarium fungi. This study aimed to investigate the effect of these feed contaminants on the intestinal morphology and microbiota composition, and to evaluate whether FBs predispose broilers to necrotic enteritis. One-day-old broiler chicks were divided into a group fed a control diet, and a group fed a FBs contaminated diet (18.6 mg FB1+FB2/kg feed). A significant increase in the plasma sphinganine/sphingosine ratio in the FBs-treated group (0.21 ± 0.016) compared to the control (0.14 ± 0.014) indicated disturbance of the sphingolipid biosynthesis. Furthermore, villus height and crypt depth of the ileum was significantly reduced by FBs. Denaturing gradient gel electrophoresis showed a shift in the microbiota composition in the ileum in the FBs group compared to the control. A reduced presence of low-GC containing operational taxonomic units in ileal digesta of birds exposed to FBs was demonstrated, and identified as a reduced abundance of Candidatus Savagella and Lactobaccilus spp. Quantification of total Clostridium perfringens in these ileal samples, previous to experimental infection, using cpa gene (alpha toxin) quantification by qPCR showed an increase in C. perfringens in chickens fed a FBs contaminated diet compared to control (7.5 ± 0.30 versus 6.3 ± 0.24 log10 copies/g intestinal content). After C. perfringens challenge, a higher percentage of birds developed subclinical necrotic enteritis in the group fed a FBs contaminated diet as compared to the control (44.9 ± 2.22% versus 29.8 ± 5.46%). PMID:26394675

  7. Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

    Directory of Open Access Journals (Sweden)

    Deep Kwatra

    2013-01-01

    Full Text Available Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW and skin (BMSk extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.

  8. Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

    Directory of Open Access Journals (Sweden)

    Ellen B. Fung

    2015-06-01

    Full Text Available Up to 20% of adult patients with Thalassemia major (Thal live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05 and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048. Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL, showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL and insulin to glucose ratios at 120 min post glucose dose (p = 0.05. Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

  9. Bone Graft Alternatives

    Science.gov (United States)

    ... cadavers. The types of allograft bone used for spine surgery include fresh frozen and lyophilized (freeze dried). The ... the most common uses of bone grafts in spine surgery is during spinal fusion. The use of autogenous ...

  10. Bone Loss in IBD

    Science.gov (United States)

    ... DENSITY? Although bone seems as hard as a rock, it’s actually living tissue. Throughout your life, old ... available Bone Loss (.pdf) File: 290 KB 733 Third Avenue, Suite 510, New York, NY 10017 | 800- ...

  11. Bone mineral density test

    Science.gov (United States)

    ... Paula FJA, Black DM, Rosen CJ. Osteoporosis and bone biology.In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, ... Bone-density testing interval and transition to osteoporosis in ...

  12. Bone mineral density test

    Science.gov (United States)

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

  13. Smoking and Bone Health

    Science.gov (United States)

    ... It has been called a childhood disease with old age consequences because building healthy bones in youth helps ... stronger. Weight-bearing exercise that forces you to work against gravity is the best exercise for bone. ...

  14. Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

    DEFF Research Database (Denmark)

    Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels;

    2015-01-01

    , whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing for a...

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

    Science.gov (United States)

    Singh, Atul Kumar; Gajiwala, Astrid Lobo; Rai, Ratan Kumar; Khan, Mohd Parvez; Singh, Chandan; Barbhuyan, Tarun; Vijayalakshmi, S; Chattopadhyay, Naibedya; Sinha, Neeraj; Kumar, Ashutosh; Bellare, Jayesh R

    2016-05-01

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

  16. Bone regeneration in dentistry

    OpenAIRE

    Tonelli, Paolo; Duvina, Marco; Barbato, Luigi; Biondi, Eleonora; Nuti, Niccolò; Brancato, Leila; Rose, Giovanna Delle

    2011-01-01

    The edentulism of the jaws and the periodontal disease represent conditions that frequently leads to disruption of the alveolar bone. The loss of the tooth and of its bone of support lead to the creation of crestal defects or situation of maxillary atrophy. The restoration of a functional condition involves the use of endosseous implants who require adequate bone volume, to deal with the masticatory load. In such situations the bone need to be regenerated, taking advantage of the biological p...

  17. Eating disorders and bone.

    Science.gov (United States)

    Tomlinson, Dale; Morgan, Sarah L

    2013-01-01

    Low bone mineral density (BMD) is a frequent and often-overlooked consequence of eating disorders, in particular anorexia nervosa and eating disorders associated with the female athlete triad. The causes of low BMD are multifactorial and include low peak bone mass accrual, accelerated bone resorption, and changes in bone microarchitecture. Early diagnosis and interventions focused on nutritional rehabilitation and weight gain reduce the risk of further BMD deficits and fractures. PMID:24094471

  18. Bone densitometry and osteoporosis

    International Nuclear Information System (INIS)

    The purpose of this book is to provide a perspective on the current status of bone densitometry and its relevance to osteoporosis diagnosis and management. Therefore, this book will give the reader an introduction to the nature of osteoporosis, its pathophysiology and epidemiology, and the clinical consequences of performing bone densitometry. Aside from standard bone densitometry, newer technologies such as quantitative ultrasound techniques, magnetic resonance imaging and bone structure analysis are discussed in the context of diagnosing osteoporosis. (orig.)

  19. BONE MECHANOTRANSDUCTION: A REVIEW

    OpenAIRE

    Reis, Joana; Capela e Silva, Fernando; Queiroga, Cristina; Lucena, Sónia; Potes, José

    2011-01-01

    This review focus on the bone physiology and mechanotransduction elements and mechanisms. Bone biology and architecture is deeply related to the mechanical environment. Orthopaedic implants cause profound changes in the biomechanics and electrophysiology of the skeleton. In the context of biomedical engineering, a deep reflexion on bone physiology and electromechanics is needed. Strategic development of new biomaterials and devices that respect and promote continuity with bone str...

  20. Three-dimensional geometric analysis of felid limb bone allometry.

    Directory of Open Access Journals (Sweden)

    Michael Doube

    Full Text Available BACKGROUND: Studies of bone allometry typically use simple measurements taken in a small number of locations per bone; often the midshaft diameter or joint surface area is compared to body mass or bone length. However, bones must fulfil multiple roles simultaneously with minimum cost to the animal while meeting the structural requirements imposed by behaviour and locomotion, and not exceeding its capacity for adaptation and repair. We use entire bone volumes from the forelimbs and hindlimbs of Felidae (cats to investigate regional complexities in bone allometry. METHOD/PRINCIPAL FINDINGS: Computed tomographic (CT images (16435 slices in 116 stacks were made of 9 limb bones from each of 13 individuals of 9 feline species ranging in size from domestic cat (Felis catus to tiger (Panthera tigris. Eleven geometric parameters were calculated for every CT slice and scaling exponents calculated at 5% increments along the entire length of each bone. Three-dimensional moments of inertia were calculated for each bone volume, and spherical radii were measured in the glenoid cavity, humeral head and femoral head. Allometry of the midshaft, moments of inertia and joint radii were determined. Allometry was highly variable and related to local bone function, with joint surfaces and muscle attachment sites generally showing stronger positive allometry than the midshaft. CONCLUSIONS/SIGNIFICANCE: Examining whole bones revealed that bone allometry is strongly affected by regional variations in bone function, presumably through mechanical effects on bone modelling. Bone's phenotypic plasticity may be an advantage during rapid evolutionary divergence by allowing exploitation of the full size range that a morphotype can occupy. Felids show bone allometry rather than postural change across their size range, unlike similar-sized animals.

  1. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

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

    2002-01-01

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

  2. Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength.

    Science.gov (United States)

    Zhang, Minjie; Feigenson, Marina; Sheu, Tzong-jen; Awad, Hani A; Schwarz, Edward M; Jonason, Jennifer H; Loiselle, Alayna E; O'Keefe, Regis J

    2015-03-01

    PGE2 exerts anabolic and catabolic effects on bone through the discrete actions of four prostanoid receptors (EP1-4). We have previously demonstrated that loss EP1 accelerates fracture repair by enhancing bone formation. In the present study we defined the role of EP1 in bone maintenance and homeostasis during aging and in response to ovariectomy. The femur and L4 vertebrae of wild type (WT) and EP1(-/-) mice were examined at 2-months, 6-months, and 1-year of age, and in WT and EP1(-/-) mice following ovariectomy (OVX) or sham surgery. Bone volume fraction, trabecular architecture and mechanical properties were maintained during aging in EP1(-/-) mice to a greater degree than age-matched WT mice. Moreover, significant increases in bone formation rate (BFR) (+60%) and mineral apposition rate (MAR) (+50%) were observed in EP1(-/-), relative to WT, while no change in osteoclast number and osteoclast surface were observed. Following OVX, loss of EP1 was protective against bone loss in both femur and L4 vertebrae, with increased bone volume/total volume (BV/TV) (+32% in femur) and max load at failure (+10% in femur) relative to WT OVX, likely resulting from the increased bone formation rate that was observed in these mice. Taken together these studies identify inhibition of EP1 as a potential therapeutic approach to suppress bone loss in aged or post-menopausal patients. PMID:25446888

  3. Oxidative stress homeostasis in grapevine (Vitis vinifera L.

    Directory of Open Access Journals (Sweden)

    Luisa C Carvalho

    2015-03-01

    Full Text Available Plants can maintain growth and reproductive success by sensing changes in the environment and reacting through mechanisms at molecular, cellular, physiological and developmental levels. Each stress condition prompts a unique response although some overlap between the reactions to abiotic stress (drought, heat, cold, salt or high light and to biotic stress (pathogens does occur. A common feature in the response to all stresses is the onset of oxidative stress, through the production of reactive oxygen species (ROS. As hydrogen peroxide and superoxide are involved in stress signaling, a tight control in ROS homeostasis requires a delicate balance of systems involved in their generation and degradation. If the plant lacks the capacity to generate scavenging potential, this can ultimately lead to death. In grapevine, antioxidant homeostasis can be considered at whole plant levels and during the development cycle. The most striking example lies in berries and their derivatives, such as wine, with nutraceutical properties associated with their antioxidant capacity. Antioxidant homeostasis is tightly regulated in leaves, assuring a positive balance between photosynthesis and respiration, explaining the tolerance of many grapevine varieties to extreme environments.In this review we will focus on antioxidant metabolites, antioxidant enzymes, transcriptional regulation and cross-talk with hormones prompted by abiotic stress conditions. We will also discuss three situations that require specific homeostasis balance: biotic stress, the oxidative burst in berries at veraison and in vitro systems. The genetic plasticity of the antioxidant homeostasis response put in evidence by the different levels of tolerance to stress presented by grapevine varieties will be addressed. The gathered information is relevant to foster varietal adaptation to impending climate changes, to assist breeders in choosing the more adapted varieties and to suitable viticulture

  4. Disruption of iron homeostasis in mesothelial cells after talc pleurodesis.

    Science.gov (United States)

    Ghio, Andrew J; Soukup, Joleen M; Dailey, Lisa A; Richards, Judy H; Turi, Jennifer L; Pavlisko, Elizabeth N; Roggli, Victor L

    2012-01-01

    The mechanism for biological effects after exposure to particles is incompletely understood. One postulate proposed to explain biological effects after exposure to particles involves altered iron homeostasis in the host. The fibro-inflammatory properties of mineral oxide particles are exploited therapeutically with the instillation of massive quantities of talc into the pleural space, to provide sclerosis. We tested the postulates that (1) in vitro exposure to talc induces a disruption in iron homeostasis, oxidative stress, and a biological effect, and (2) talc pleurodesis in humans alters iron homeostasis. In vitro exposures of both mesothelial and airway epithelial cells to 100 μg/ml talc significantly increased iron importation and concentrations of the storage protein ferritin. Using dichlorodihydrofluorescein, exposure to talc was associated with a time-dependent and concentration-dependent generation of oxidants in both cell types. The expression of proinflammatory mediators was also increased after in vitro exposures of mesothelial and airway epithelial cells to talc. Relative to control lung tissue, lung tissue from patients treated with sclerodesis demonstrated an accumulation of iron and increased expression of iron-related proteins, including ferritin, the importer divalent metal transport-1 and the exporter ferroportin-1. Talc was also observed to translocate to the parenchyma, and changes in iron homeostasis were focally distributed to sites of retention. We conclude that exposure to talc disrupts iron homeostasis, is associated with oxidative stress, and results in a biological effect (i.e., a fibro-inflammatory response). Talc pleurodesis can function as a model of the human response to mineral oxide particle exposure, albeit a massive one. PMID:22210826

  5. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

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

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy. PMID:25579825

  6. Menopause and Bone Loss

    Science.gov (United States)

    Fact Sheet & Menopause Bone Loss How are bone loss and menopause related? Throughout life your body keeps a balance between the loss ... The sooner you take steps to prevent bone loss, the lower your risk of osteoporosis later in life. If you are skipping menstrual periods, have had ...

  7. What's a Funny Bone?

    Science.gov (United States)

    ... Help White House Lunch Recipes What's a Funny Bone? KidsHealth > For Kids > What's a Funny Bone? Print A A A Text Size Have you ... prickly kind of dull pain? That's your funny bone! It doesn't really hurt as much as ...

  8. A unified theory of bone healing and nonunion: BHN theory.

    Science.gov (United States)

    Elliott, D S; Newman, K J H; Forward, D P; Hahn, D M; Ollivere, B; Kojima, K; Handley, R; Rossiter, N D; Wixted, J J; Smith, R M; Moran, C G

    2016-07-01

    This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91. PMID:27365465

  9. Can Endocrine disrupters interfere with Ca2+ homeostasis in invertebrate cells?

    Directory of Open Access Journals (Sweden)

    L. Canesi

    2010-01-01

    Full Text Available A wide range of environmental chemicals have been shown to alter the endocrine system of both wildlife and humans. There is increasing evidence that many of these endocrine disruptors (EDs, in particular estrogenic chemicals, can rapidly affect cellular homeostasis and signaling in mammalian Ca2+ systems. In this work, in vitro and in vivo data are summarised on the effects of different compounds known or suspected as EDs on homeostasis in Ca2+ marine invertebrate, the blue mussel Mytilus spp. Both synthetic estrogens and different EDs (DES, BPA, NP, PCB congeners, etc. rapidly increased sytosolic [Ca2+] in mussel hemosytes, as evaluated by FURA2 single cell fluorescence microscopy. The observed [Ca2+] increase was unaffected by the antiestrogen Tamoxifen and was due to either increased influx or release from Ca2+ intracellular stores, depending on the compound. Moreover, different ED,s including the brominated flame retardant TBBPA (tetrabromo bisphenol A induced a dose-dependent inhibition of the plasma membrane Ca2+ -ATPase (PMCA activity from mussel gills in vitro, this supporting a direct effect on membrane pumps. The in vitro effects of EDs were observed at concentrations generally higher than those of E2. However, in vivo, mussel exposure to environmetal concentrations of Bisphenol A (BPA and of the polybrominated diphenyl ether TBDE-47 resulted in large inhibition of PMCA activity in the digestive gland. The results indicate that, in invertebrate like in mammalian systems, interference with Ca2+ homeostasis may represent a significant mode of action of a variety of EDs.

  10. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Josep Bassaganya-Riera

    Full Text Available BACKGROUND: There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(- strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM and increased adipose tissue regulatory T cells (Treg cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4 in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. CONCLUSIONS/SIGNIFICANCE: Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.

  11. Intermittent negative pressure affects tendon-bone healing after anterior cruciate ligament reconstruction%间歇性负压干预前交叉韧带重建后的腱-骨愈合

    Institute of Scientific and Technical Information of China (English)

    孙正明; 凌鸣; 冯伟楼; 董向辉; 刘时璋; 易智

    2013-01-01

    背景:间歇性负压被证实可以促进软组织修复及骨愈合,但其对交叉韧带重建后腱-骨愈合的影响尚未见报道。  目的:观察间歇性负压对兔前交叉韧带重建后腱-骨愈合及肌腱移植物生物力学的影响。  方法:取24只新西兰大白兔制备自体半腱肌前交叉韧带重建模型,随机取一侧后腿作为负压侧,负压侧关节通过引流管接微型负压吸引器,并维持低强度、间歇性负压;对侧后腿作为对照,接普通引流管。5d后两侧同时拔除吸引管。造模后6周,取关节液检测白细胞介素1β的表达水平;取股骨-韧带-胫骨复合体行肌腱移植物拉力测定和腱-骨界面组织学观察。  结果与结论:1只兔关节感染,最终23只兔进入结果分析。拉力测定结果显示,负压组完全断裂所需拉力显著大于对照组(P OBJECTIVE:To research the effect of intermittent negative pressure on tendon-bone healing after anterior cruciate ligament reconstruction and on the biomechanics of tendon grafts. METHODS:A total of 24 New Zealand white rabbits were randomly selected to establish the models of anterior cruciate ligament reconstruction of autogenous semitendinosus. The hind leg of one side was selected randomly as the negative pressure group, and the joint of the negative pressure side was connected with the micro-negative pressure aspirator through drainage tube and maintained a low-intensity and intermittent negative pressure;the contralateral hind leg was as the control and connected with ordinary drainage tube. Drainage tubes of both sides were removed at the same time after 5 days. At 6 weeks after modeling, the joint fluid was drawn to detect the expression levels of interleukin-1β;femur-ligament-tibia complex was used for tension measurement of tendon graft, and histological observation of tendon-bone interface. RESULTS AND CONCLUSION:One rabbit had joint infection, and final y 23

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

    Science.gov (United States)

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

    2016-08-01

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

  13. Vitamin D interactions with soy isoflavones on bone after menopause: a review.

    Science.gov (United States)

    Park, Clara Y; Weaver, Connie M

    2012-11-01

    Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women. PMID:23201836

  14. Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis.

    Directory of Open Access Journals (Sweden)

    Ting-Wei Mu

    2008-02-01

    Full Text Available A lysosomal storage disease (LSD results from deficient lysosomal enzyme activity, thus the substrate of the mutant enzyme accumulates in the lysosome, leading to pathology. In many but not all LSDs, the clinically most important mutations compromise the cellular folding of the enzyme, subjecting it to endoplasmic reticulum-associated degradation instead of proper folding and lysosomal trafficking. A small molecule that restores partial mutant enzyme folding, trafficking, and activity would be highly desirable, particularly if one molecule could ameliorate multiple distinct LSDs by virtue of its mechanism of action. Inhibition of L-type Ca2+ channels, using either diltiazem or verapamil-both US Food and Drug Administration-approved hypertension drugs-partially restores N370S and L444P glucocerebrosidase homeostasis in Gaucher patient-derived fibroblasts; the latter mutation is associated with refractory neuropathic disease. Diltiazem structure-activity studies suggest that it is its Ca2+ channel blocker activity that enhances the capacity of the endoplasmic reticulum to fold misfolding-prone proteins, likely by modest up-regulation of a subset of molecular chaperones, including BiP and Hsp40. Importantly, diltiazem and verapamil also partially restore mutant enzyme homeostasis in two other distinct LSDs involving enzymes essential for glycoprotein and heparan sulfate degradation, namely alpha-mannosidosis and type IIIA mucopolysaccharidosis, respectively. Manipulation of calcium homeostasis may represent a general strategy to restore protein homeostasis in multiple LSDs. However, further efforts are required to demonstrate clinical utility and safety.

  15. The child with bone pain: malignancies and mimickers

    OpenAIRE

    McCarville, M. Beth

    2009-01-01

    Abstract Bone pain in children is common. The cause may be as benign as growing pains or as life-threatening as a malignancy. When a cause cannot be established by laboratory tests, physical examination or patient history, imaging of the affected body part is often obtained. Distinguishing benign from malignant processes involving the bones of children, based on imaging findings, can be challenging. The most common benign conditions that mimic pediatric bone tumors on imaging are Langerhan's ...

  16. Adverse Effects of Hyperlipidemia on Bone Regeneration and Strength

    OpenAIRE

    Pirih, F; J. Lu; Ye, F; Bezouglaia, O.; Atti, E.; Ascenzi, MG; Tetradis, S; Demer, LL; Aghaloo, T; Tintut, Y

    2012-01-01

    Hyperlipidemia increases the risk for generation of lipid oxidation products, which accumulate in the subendothelial spaces of vasculature and bone. Atherogenic high-fat diets increase serum levels of oxidized lipids, which are known to attenuate osteogenesis in culture and to promote bone loss in mice. In this study, we investigated whether oxidized lipids affect bone regeneration and mechanical strength. Wild type and hyperlipidemic (Ldlr−/−) mice were placed on a high-fat (HF) diet for 13 ...

  17. T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis

    OpenAIRE

    Cinalli, Ryan M.; Herman, Catherine E.; Lew, Brian O.; Wieman, Heather L.; Thompson, Craig B.; Rathmell, Jeffrey C.

    2005-01-01

    Signals that regulate T cell homeostasis are not fully understood. G protein-coupled receptors (GPCR), such as the chemokine receptors, may affect homeostasis by direct signaling or by guiding T cell migration to distinct location-restricted signals. Here, we show that blockade of Gαi-associated GPCR signaling by treatment with pertussis toxin led to T cell atrophy and shortened life-span in T cell-replete hosts and prevented T cell homeostatic growth and proliferation in T cell-deficient hos...

  18. Augmentation of tendon-to-bone healing.

    Science.gov (United States)

    Atesok, Kivanc; Fu, Freddie H; Wolf, Megan R; Ochi, Mitsuo; Jazrawi, Laith M; Doral, M Nedim; Lubowitz, James H; Rodeo, Scott A

    2014-03-19

    Tendon-to-bone healing is vital to the ultimate success of the various surgical procedures performed to repair injured tendons. Achieving tendon-to-bone healing that is functionally and biologically similar to native anatomy can be challenging because of the limited regeneration capacity of the tendon-bone interface. Orthopaedic basic-science research strategies aiming to augment tendon-to-bone healing include the use of osteoinductive growth factors, platelet-rich plasma, gene therapy, enveloping the grafts with periosteum, osteoconductive materials, cell-based therapies, biodegradable scaffolds, and biomimetic patches. Low-intensity pulsed ultrasound and extracorporeal shockwave treatment may affect tendon-to-bone healing by means of mechanical forces that stimulate biological cascades at the insertion site. Application of various loading methods and immobilization times influence the stress forces acting on the recently repaired tendon-to-bone attachment, which eventually may change the biological dynamics of the interface. Other approaches, such as the use of coated sutures and interference screws, aim to deliver biological factors while achieving mechanical stability by means of various fixators. Controlled Level-I human trials are required to confirm the promising results from in vitro or animal research studies elucidating the mechanisms underlying tendon-to-bone healing and to translate these results into clinical practice. PMID:24647509

  19. Fibrous dysplasia of bone: a clinicopathologic review

    Directory of Open Access Journals (Sweden)

    Mohan H

    2011-11-01

    Full Text Available Harsh Mohan1, Preeti Mittal1, Irneet Mundi1, Sudhir Kumar21Department of Pathology, 2Department of Orthopedics, Government Medical College, Sector 32, Chandigarh, IndiaAbstract: Fibrous dysplasia of the bones is an uncommon congenital skeletal disorder that is found equally in both genders and is not inherited. Its etiology has been linked to an activating mutation of Gsα and the downstream effects of the resultant increase in cAMP. Fibrous dysplasia is categorized as either monostotic or polyostotic, and may occur as a component of McCune-Albright syndrome or the rare Mazabraud syndrome. Long bones, skull bones, and ribs are the most commonly affected bones. The radiological picture is somewhat variable, including a ground-glass appearance, expansion of the bone, and sclerosis surrounding the lesion. Histologically, fibrous dysplasia shows irregularly-shaped trabeculae of immature, woven bone in a background of variably cellular, loosely arranged fibrous stroma. It may be complicated by pathologic fracture, and rarely by malignant transformation. This review examines interesting issues surrounding the etiology of fibrous dysplasia, its clinical and laboratory manifestations, radiological picture, utility of bone biopsy, gross and microscopic pathology, complications, and its differential diagnostic considerations.Keywords: fibrous dysplasia, McCune-Albright syndrome, monostotic form, polyostotic form

  20. Cisplatin inhibits bone healing during distraction osteogenesis.

    Science.gov (United States)

    Stine, Kimo C; Wahl, Elizabeth C; Liu, Lichu; Skinner, Robert A; Vanderschilden, Jacquelyn; Bunn, Robert C; Montgomery, Corey O; Suva, Larry J; Aronson, James; Becton, David L; Nicholas, Richard W; Swearingen, Christopher J; Lumpkin, Charles K

    2014-03-01

    Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non-cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five-dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p CDP regimen were observed in TNFR1KO mice. The two-dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri-operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP. PMID:24259375

  1. Enzymatic maceration of bone

    DEFF Research Database (Denmark)

    Uhre, Marie-Louise; Eriksen, Anne Marie; Simonsen, Kim Pilkjær;

    2015-01-01

    afterwards macerated by one of the two methods. DNA extraction was performed to see the effect of the macerations on DNA preservation. Furthermore, the bone pieces were examined in a stereomicroscope to assess for any bone damage. The results demonstrated that both methods removed all flesh/soft tissue from...... the bones. The DNA analysis showed that DNA was preserved on all the pieces of bones which were examined. Finally, the investigation suggests that enzyme maceration could be gentler on the bones, as the edges appeared less frayed. The enzyme maceration was also a quicker method; it took three hours...

  2. Tin in Human Bones

    OpenAIRE

    Jambor, Jaroslav; Smreka, Vâclav

    1993-01-01

    TIN IN HUMAN BONES. The tin content in the bones of 149 skeletons from the 1st - 5th centuries A.D., and of 11 individuals of the recent population was determined. The bone samples were carbonized and analyzed through emission spectroscopy with a.c. excitation. The tin content in bones of recent populations not exposed to extra tin supply is about one order of magnitude higher than is the case with the bones od some populations that lived at the beginning of our era. The distribut...

  3. New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

    Energy Technology Data Exchange (ETDEWEB)

    Herlin, Maria, E-mail: maria.herlin@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: p.zioupos@cranfield.ac.uk [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: antti.aula@gmail.com [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: juha.risteli@ppshp.fi [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: timo.jamsa@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: juha.tuukkanen@oulu.fi [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: merja.korkalainen@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: Helen.Hakansson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: matti.viluksela@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)

    2013-11-15

    results in increased trabecular bone and softer cortical bone. • TCDD does not affect the bones of Ahr{sup –/–} mice.

  4. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis.

    Science.gov (United States)

    Salahudeen, Ameen A; Thompson, Joel W; Ruiz, Julio C; Ma, He-Wen; Kinch, Lisa N; Li, Qiming; Grishin, Nick V; Bruick, Richard K

    2009-10-30

    Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of genes responsible for iron uptake, release, use, and storage through the actions of the iron regulatory proteins IRP1 and IRP2. However, the manner in which iron levels are sensed to affect IRP2 activity is poorly understood. We found that an E3 ubiquitin ligase complex containing the FBXL5 protein targets IRP2 for proteasomal degradation. The stability of FBXL5 itself was regulated, accumulating under iron- and oxygen-replete conditions and degraded upon iron depletion. FBXL5 contains an iron- and oxygen-binding hemerythrin domain that acted as a ligand-dependent regulatory switch mediating FBXL5's differential stability. These observations suggest a mechanistic link between iron sensing via the FBXL5 hemerythrin domain, IRP2 regulation, and cellular responses to maintain mammalian iron homeostasis. PMID:19762597

  5. Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S; Schousboe, Arne;

    2010-01-01

    Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affected...... by these conditions. [1-(13)C]glucose was administered to Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats. Sprague-Dawley (SprD), Zucker lean (ZL), and ZDF lean rats were used as controls. Several brain regions were analyzed for glycogen levels along with (13)C-labeling and content of....... The MCL ratios of glutamine and glutamate were decreased in the cerebellum of the ZO and the ZDF rats. Glycogen levels were also lower in this region. These results suggest that the obese and type 2 diabetic models were associated with lower brain glucose metabolism. Glucose metabolism through the TCA...

  6. Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling.

    Science.gov (United States)

    Zheng, Xi; Lee, Sun-Kyeong; Chun, Ock K

    2016-01-01

    Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

  7. A potential kidney-bone axis involved in the rapid minute-to-minute regulation of plasma Ca2+

    DEFF Research Database (Denmark)

    Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Olgaard, Klaus; Lewin, Ewa

    2015-01-01

    BACKGROUND: Understanding the regulation of mineral homeostasis and function of the skeleton as buffer for Calcium and Phosphate has regained new interest with introduction of the syndrome "Chronic Kidney Disease-Mineral and Bone Disorder"(CKD-MBD). The very rapid minute-to-minute regulation of p...

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

    Directory of Open Access Journals (Sweden)

    Agata Witkowska

    2014-10-01

    at which most guinea pigs have reached full weight. This study is the first to show the high abundance (100% in this study of the supratrochlear foramen within the guinea pig humerus and the complete absence of a supracondylar foramen, which is different to many other species and may also affect potential fracture points and frequencies. Understanding bone morphology and growth is essential in not only understanding the requirements of the healthy guinea pig, but also necessary in order to investigate disease states.

  9. Periprosthetic fracture fixation in osteoporotic bone.

    Science.gov (United States)

    Lenz, Mark; Lehmann, Wolfgang; Wähnert, Dirk

    2016-06-01

    Fixation techniques of periprosthetic fractures are far from ideal although the number of this entity is rising. The presence of an intramedullary implant generates its own fracture characteristics since stiffness is altered along the bone shaft and certain implant combinations affect load resistance of the bone. Influencing factors are cement fixation of the implant, intramedullary locking and extramedullary or intramedullary localization of the implant and the cortical thickness of the surrounding bone. Cerclage wires are ideally suited to fix radially displaced fragments around an intramedullary implant but they are susceptible to axial and torsional load. Screws should be added if these forces have to be neutralized. Stability of the screw fixation itself can be enhanced by embracement configuration around the intramedullary implant. Poor bone stock quality, often being present in metaphyseal areas limits screw fixation. Cement augmentation is an attractive option in this field to enhance screw purchase. PMID:27338227

  10. Bone pain: current and future treatments.

    Science.gov (United States)

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

    2016-06-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities. PMID:26940053

  11. Bone stress injuries

    International Nuclear Information System (INIS)

    Bone stress injuries are due to cyclical overuse of the bone. They are relatively common in athletes and military recruits but also among otherwise healthy people who have recently started new or intensive physical activity. Diagnosis of bone stress injuries is based on the patient's history of increased physical activity and on imaging findings. The general symptom of a bone stress injury is stress-related pain. Bone stress injuries are difficult to diagnose based only on a clinical examination because the clinical symptoms may vary depending on the phase of the pathophysiological spectrum in the bone stress injury. Imaging studies are needed to ensure an early and exact diagnosis, because if the diagnosis is not delayed most bone stress injuries heal well without complications

  12. Nuclear Localised MORE SULPHUR ACCUMULATION1 Epigenetically Regulates Sulphur Homeostasis in Arabidopsis thaliana.

    Science.gov (United States)

    Huang, Xin-Yuan; Chao, Dai-Yin; Koprivova, Anna; Danku, John; Wirtz, Markus; Müller, Steffen; Sandoval, Francisco J; Bauwe, Hermann; Roje, Sanja; Dilkes, Brian; Hell, Rüdiger; Kopriva, Stanislav; Salt, David E

    2016-09-01

    Sulphur (S) is an essential element for all living organisms. The uptake, assimilation and metabolism of S in plants are well studied. However, the regulation of S homeostasis remains largely unknown. Here, we report on the identification and characterisation of the more sulphur accumulation1 (msa1-1) mutant. The MSA1 protein is localized to the nucleus and is required for both S-adenosylmethionine (SAM) production and DNA methylation. Loss of function of the nuclear localised MSA1 leads to a reduction in SAM in roots and a strong S-deficiency response even at ample S supply, causing an over-accumulation of sulphate, sulphite, cysteine and glutathione. Supplementation with SAM suppresses this high S phenotype. Furthermore, mutation of MSA1 affects genome-wide DNA methylation, including the methylation of S-deficiency responsive genes. Elevated S accumulation in msa1-1 requires the increased expression of the sulphate transporter genes SULTR1;1 and SULTR1;2 which are also differentially methylated in msa1-1. Our results suggest a novel function for MSA1 in the nucleus in regulating SAM biosynthesis and maintaining S homeostasis epigenetically via DNA methylation. PMID:27622452

  13. The dual oxidase gene BdDuox regulates the intestinal bacterial community homeostasis of Bactrocera dorsalis.

    Science.gov (United States)

    Yao, Zhichao; Wang, Ailin; Li, Yushan; Cai, Zhaohui; Lemaitre, Bruno; Zhang, Hongyu

    2016-05-01

    The guts of metazoans are in permanent contact with the microbial realm that includes beneficial symbionts, nonsymbionts, food-borne microbes and life-threatening pathogens. However, little is known concerning how host immunity affects gut bacterial community. Here, we analyze the role of a dual oxidase gene (BdDuox) in regulating the intestinal bacterial community homeostasis of the oriental fruit fly Bactrocera dorsalis. The results showed that knockdown of BdDuox led to an increased bacterial load, and to a decrease in the relative abundance of Enterobacteriaceae and Leuconostocaceae bacterial symbionts in the gut. The resulting dysbiosis, in turn, stimulates an immune response by activating BdDuox and promoting reactive oxygen species (ROS) production that regulates the composition and structure of the gut bacterial community to normal status by repressing the overgrowth of minor pathobionts. Our results suggest that BdDuox plays a pivotal role in regulating the homeostasis of the gut bacterial community in B. dorsalis. PMID:26565723

  14. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    Directory of Open Access Journals (Sweden)

    Juan Cristóbal Conde-Pérezprina

    2012-01-01

    Full Text Available The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”. The DNA mismatch repair system (MMR is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others.

  15. Aluminum neurotoxicity effects on intracellular Ca2+homeostasis in the rat cerebral cortex

    Institute of Scientific and Technical Information of China (English)

    Rui Ren; Yang Zhang; Xiaofeng Zhang; Yanping Wu; Dandan Zhang; Baixiang Li

    2010-01-01

    Studies have suggested that aluminum,a neurotoxic metal,is involved in the progression of neurodegenerative diseases.Previous studies have confirmed that aluminum influences intracellular Ca2+homeostasis.However,it remains unclear whether aluminum increases or decreases intracellular Ca2+concentrations.The present study demonstrated that Al3+competitively binds to calmodulin(CAM),together with Ca2+,which resulted in loss of capacity of CaM to bind to Ca2+,leading to increased[Ca2+],.Al3+stimulated voltage-gated calcium channels on cell membranes,which allowed a small quantity of Ca2+into the cells.Al3+also promoted calcium release from organelles by stimulating L-Ca2+α1c to trigger calcium-induced calcium release.Although Al3+upregulated expression of Na+/Ca2+exchanger mRNA,increased levels of Ca2+and Na+/Ca2+exchanger did not maintain a normal Ca2+balance.Al3+resulted in disordered intracellular calcium homeostasis by affecting calcium channels,calcium buffering,and calcium expulsion.

  16. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    International Nuclear Information System (INIS)

    Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process

  17. Consolidation of massive bone allografts in limb-preserving operations for bone tumours

    OpenAIRE

    San-Julian, M.; Leyes, M.; Mora, G. (Gonzalo); Cañadell, J.M. (J. M.)

    1995-01-01

    This study analysed the influence of several factors affecting the consolidation time of 83 massive bone allografts in 79 patients with malignant bone tumours: osteosarcoma 57; Ewing's sarcoma 8; malignant fibrous histiocytoma 3; chondrosarcoma 4; fibrosarcoma 5; and giant cell tumours 2. The mean age of the patients was 19 years and the mean length of the allografts was 18 cm. The minimum follow up was for 12 months. The mean consolidation time for metaphyseal and diaphyseal osteotomies was ...

  18. The use of implantable bone stimulators in nonunion treatment.

    Science.gov (United States)

    Hughes, Michael S; Anglen, Jeffrey O

    2010-03-01

    Delayed or failure of bone healing in fracture, osteotomy, and arthrodesis patients continues to be a clinical dilemma. Electromagnetic stimulation is 1 modality demonstrated in many studies to aid bone healing; however, relatively few studies depict the use and complications associated with direct current implantable bone stimulators. Over a 9-year period, we studied a consecutive series of 120 adult patients who underwent implantation of a direct current bone stimulator. The goals of this study were to determine the time until healing, the presence of infection, and the need for additional nonunion surgery or salvage procedure following internal bone stimulator placement for nonunion treatment. Of the factors affecting the time until healing, tobacco smoking was a significant factor associated with increased time until healing. Tobacco smoking and duration of nonunion prior to implantable bone stimulator placement were both significant factors in the need for revision nonunion surgery or salvage procedure after implantable bone stimulator placement. Deep soft tissue infection or osteomyelitis was a significant factor predicting prolonged time to healing, subsequent infection following implantable bone stimulator placement, and the need for revision or salvage surgery. With the relative lack of complications directly attributable to electromagnetic implantable bone stimulators, their use may be an effective adjuvant to stable internal fixation and autogenous bone grafting in healing nonunions. However, the use of implantable bone stimulators in patients with nonunion prior to deep soft tissue infection or osteomyelitis exhibited an increased rate of postoperative infection in this study. PMID:20349861

  19. Bone repair: Effects of physical exercise and LPS systemic exposition.

    Science.gov (United States)

    Nogueira, Jonatas E; Branco, Luiz G S; Issa, João Paulo M

    2016-08-01

    Bone repair can be facilitated by grafting, biochemical and physical stimulation. Conversely, it may be delayed lipopolysaccharide (LPS). Physical exercise exerts beneficial effects on the bone, but its effect on bone repair is not known. We investigated the effect of exercise on the LPS action on bone healing through bone densitometry, quantitative histological analysis for bone formation rate and immunohistochemical markers in sedentary and exercised animals. Rats ran on the treadmill for four weeks. After training the rats were submitted to a surgical procedure (bone defect in the right tibia) and 24h after the surgery LPS was administered at a dose of 100μg/kg i.p., whereas the control rats received a saline injection (1ml/kg, i.p.). Right tibias were obtained for analysis after 10days during which rats were not submitted to physical training. Physical exercise had a positive effect on bone repair, increasing bone mineral density, bone mineral content, bone formation rate, type I collagen and osteocalcin expression. These parameters were not affected by systemic administration of LPS. Our data indicate that physical exercise has an important osteogenic effect, which is maintained during acute systemic inflammation induced by exposure to a single dose of LPS. PMID:27319388

  20. Stretched exponential relaxation of piezovoltages in wet bovine bone.

    Science.gov (United States)

    Xu, Lianyun; Hou, Zhende; Fu, Donghui; Qin, Qing-Hua; Wang, Yihan

    2015-01-01

    It is important to determine the amplitude and variation characteristics of piezovoltage in wet bone, which can, in turn, be taken as a basis for studying whether electrical signals induced by external forces can affect the growth of bone cells. This work measured the characteristics of piezoelectric effects under dynamic and static loading. The results show that the variations of piezovoltage in wet bone in both loading and load holding periods follow a stretched exponential relaxation law, and the relaxation time constants of the piezovoltages are much larger than those of dry bone. This finding means that the active time of piezovoltage in wet bone is much longer than that of dry bone. Regardless of the loading and load holding processes, continuously increasing deformation in wet bone caused piezoelectric charges to be continuously induced and increased the dielectric constant of wet bone along with the deformation process. In general, compared with piezovoltage in dry bone, that in wet bone had lower amplitude and could exist for a longer duration. It can be inferred, therefore, that piezoelectricity might create coupling with the streaming potential in bone by changing the thickness of the double electrode layer. PMID:25460408