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Sample records for mononucleated macrophage resorption

  1. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    PubMed

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.

  2. Evidence that Resorption of Bone by Rat Peritoneal Macrophages Occurs in an Acidic Environment

    NASA Technical Reports Server (NTRS)

    Blair, H. C.

    1985-01-01

    Skeletal loss in space, like any form of osteoporosis, reflects a relative imbalance of the activities of cells resorbing (degrading) or forming bone. Consequently, prevention of weightlessness induced bone loss may theoretically be accomplished by (1) stimulating bone formation or (2) inhibiting bone resorption. This approach, however, requires fundamental understanding of the mechanisms by which cells form or degrade bone, information not yet at hand. An issue central to bone resorption is the pH at which resorption takes place. The pH dependent spectral shift of a fluorescent dye (fluorescein isothiocyanate) conjugated to bone matrix was used to determine the pH at the resorptive cell bone matrix interface. Devitalized rat bone was used as the substrate, and rat peritoneal macrophages were used as the bone resorbing cells. The results suggest that bone resorption is the result of generation of an acidic microenvironment at the cell matrix junction.

  3. Response of three murine macrophage populations to particulate debris: bone resorption in organ cultures.

    PubMed

    Glant, T T; Jacobs, J J

    1994-09-01

    Particulate wear debris from bone cement or prosthetic components can stimulate macrophages to cause bone resorption. We compared the effect of particle composition (titanium and polymethylmethacrylate as inherent components of prosthetic materials or bone cement and polystyrene as a reference material) on the secretion of interleukin-1 and prostaglandin E2 by peritoneal macrophages and monocyte/macrophage cell lines (P388D1 and IC-21) and on the bone-resorbing activity of conditioned medium harvested from these particle-challenged macrophages. Titanium particles (1-3 microns) in peritoneal macrophage cultures exhibited significantly enhanced bone-resorbing activity measured as 45Ca release, whereas polymethylmethacrylate and polystyrene exhibited this effect to a greater extent in the P388D1 and IC-21 monocyte/macrophage cultures. Although exogenous prostaglandin E2 and recombinant human interleukin-1 could significantly increase the 45Ca release and indomethacin significantly reduced both the spontaneous calcium efflux and active 45Ca release from calvarial bones labeled in vivo, the levels of interleukin-1 and prostaglandin E2, alone or together, did not always correlate with the bone-resorbing activity of conditioned media. Thus, the actual levels of potent bone-resorbing agents (prostaglandin E2 and interleukin-1) measured in conditioned tissue culture media did not necessarily reflect the bone-resorbing capability. An important result of this study is that different macrophage populations may respond differently to the same microenvironmental signal, which in our investigation was particulate wear debris of differing composition and size. PMID:7931789

  4. Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages.

    PubMed

    Kim, Yun-Ho; Kim, Jung-Lye; Lee, Eun-Jung; Park, Sin-Hye; Han, Seon-Young; Kang, Soon Ah; Kang, Young-Hee

    2014-03-01

    Osteoclastogenesis is comprised of several stage s including progenitor survival, differentiation to mononuclear preosteoclasts, cell fusion to multinuclear mature osteoclasts, and activation to osteoclasts with bone resorbing activity. Botanical antioxidants are now being increasingly investigated for their health-promoting effects on bone. This study investigated that fisetin, a flavonol found naturally in many fruits and vegetables, suppressed osteoclastogenesis by disturbing receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated signaling pathway and demoting osteoclastogenic protein induction. Nontoxic fisetin at ≤10 μM inhibited the induction of RANK, tumor necrosis factor receptor associated factor 6 (TRAF6) and the activation of NF-κB in RANKL-stimulated RAW 264.7 macrophages. In RANKL-differentiated osteoclasts cell fusion protein of E-cadherin was induced, which was dampened by fisetin. The formation of tartrate-resistance acid phosphatase-positive multinucleated osteoclasts was suppressed by adding fisetin to RANKL-exposed macrophages. It was also found that fisetin reduced actin ring formation and gelsolin induction of osteclasts enhanced by RANKL through disturbing c-Src-proline-rich tyrosine kinase 2 signaling. Fisetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton to seal the resorbing area and to secret protons for bone resorption. Consistently, the 5 day-treatment of fisetin diminished RANKL-induced cellular expression of carbonic anhydrase II and integrin β3 concurrently with a reduction of osteoclast bone-resorbing activity. Therefore, fisetin was a natural therapeutic agent retarding osteoclast fusion and cytoskeletal organization such as actin rings and ruffled boarder, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone.

  5. VIP treatment prevents embryo resorption by modulating efferocytosis and activation profile of maternal macrophages in the CBAxDBA resorption prone model

    PubMed Central

    Gallino, Lucila; Calo, Guillermina; Hauk, Vanesa; Fraccaroli, Laura; Grasso, Esteban; Vermeulen, Mónica; Leirós, Claudia Pérez; Ramhorst, Rosanna

    2016-01-01

    Successful embryo implantation occurs followed by a local pro-inflammatory response subsequently shifted toward a tolerogenic one. VIP (vasoactive intestinal peptide) has embryotrofic, anti-inflammatory and tolerogenic effects. In this sense, we investigated whether the in vivo treatment with VIP contributes to an immunosuppressant local microenvironment associated with an improved pregnancy outcome in the CBA/J × DBA/2 resorption prone model. Pregnancy induced the expression of VIP, VPAC1 and VPAC2 in the uterus from CBA/J × DBA/2 mating females on day 8.5 of gestation compared with non-pregnant mice. VIP treatment (2 nmol/mouse i.p.) on day 6.5 significantly increased the number of viable implantation sites and improved the asymmetric distribution of implanted embryos. This effect was accompanied by a decrease in RORγt and an increase in TGF-β and PPARγ expression at the implantation sites. Moreover, VIP modulated the maternal peritoneal macrophages efferocytosis ability, tested using latex beads-FITC or apoptotic thymocytes, displaying an increased frequency of IL-10-producer F4/80 cells while did not modulate TNF-α and IL-12 secretion. The present data suggest that VIP treatment increases the number of viable embryos associated with an increase in the efferocytic ability of maternal macrophages which is related to an immunosuppressant microenvironment. PMID:26733206

  6. Differentiation analyses of adult suspension mononucleated peripheral blood cells of Mus musculus

    PubMed Central

    2010-01-01

    Background The purpose of this study is to determine whether isolated suspension mouse peripheral mononucleated blood cells have the potential to differentiate into two distinct types of cells, i.e., osteoblasts and osteoclasts. Results Differentiation into osteoblast cells was concomitant with the activation of the Opn gene, increment of alkaline phosphatase (ALP) activity and the existence of bone nodules, whereas osteoclast cells activated the Catk gene, increment of tartrate resistant acid phosphatase (TRAP) activity and showed resorption activities via resorption pits. Morphology analyses showed the morphology of osteoblast and osteoclast cells after von Kossa and May-Grunwald-Giemsa staining respectively. Conclusions In conclusion, suspension mononucleated cells have the potentiality to differentiate into mature osteoblasts and osteoclasts, and hence can be categorized as multipotent stem cells. PMID:20969794

  7. CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection-Driven Bone Resorption.

    PubMed

    Steinmetz, Orit; Hoch, Shifra; Avniel-Polak, Shani; Gavish, Keren; Eli-Berchoer, Luba; Wilensky, Asaf; Nussbaum, Gabriel

    2016-05-01

    Porphyromonas gingivalis,an anaerobic bacterium strongly linked to infection-driven inflammatory bone erosion, thrives within a highly inflamed milieu and disseminates to distant sites, such as atherosclerotic plaque. We examined the role of monocyte/macrophages in determining the outcome of infection with P. gingivalis. Surprisingly, transient monocyte/macrophage depletion led to greatly improved clearance of P. gingivalis. The chemokine receptors CCR2 and CX3CR1 play a major role in monocyte recruitment and differentiation to Ly6C(hi) vs CX3CR1(hi) subsets, respectively. To determine the contribution of particular monocyte/macrophage subsets to bacterial survival, we challenged chemokine receptor knockout mice and found that P. gingivalis clearance is significantly improved in the absence of CX3CR1. CX3CR1(hi) monocyte/macrophages promote P. gingivalis survival by downregulating neutrophil phagocytosis. Furthermore, CX3CR1 knockout mice resist bone resorption in the oral cavity following challenge with P. gingivalis Our findings provide an explanation for bacterial coexistence alongside an activate neutrophil infiltrate. PMID:26704610

  8. Commercial Honeybush (Cyclopia spp.) Tea Extract Inhibits Osteoclast Formation and Bone Resorption in RAW264.7 Murine Macrophages-An in vitro Study.

    PubMed

    Visagie, Amcois; Kasonga, Abe; Deepak, Vishwa; Moosa, Shaakirah; Marais, Sumari; Kruger, Marlena C; Coetzee, Magdalena

    2015-10-28

    Honeybush tea, a sweet tasting caffeine-free tea that is indigenous to South Africa, is rich in bioactive compounds that may have beneficial health effects. Bone remodeling is a physiological process that involves the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. When resorption exceeds formation, bone remodeling can be disrupted resulting in bone diseases such as osteoporosis. Osteoclasts are multinucleated cells derived from hematopoietic precursors of monocytic lineage. These precursors fuse and differentiate into mature osteoclasts in the presence of receptor activator of NF-kB ligand (RANKL), produced by osteoblasts. In this study, the in vitro effects of an aqueous extract of fermented honeybush tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macrophages. We found that commercial honeybush tea extract inhibited osteoclast formation and TRAP activity which was accompanied by reduced bone resorption and disruption of characteristic cytoskeletal elements of mature osteoclasts without cytotoxicity. Furthermore, honeybush tea extract decreased expression of key osteoclast specific genes, matrix metalloproteinase-9 (MMP-9), tartrate resistant acid phosphatase (TRAP) and cathepsin K. This study demonstrates for the first time that honeybush tea may have potential anti-osteoclastogenic effects and therefore should be further explored for its beneficial effects on bone.

  9. 2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling.

    PubMed

    Park, So Jeong; Park, Doo Ri; Bhattarai, Deepak; Lee, Kyeong; Kim, Jaesang; Bae, Yun Soo; Lee, Soo Young

    2014-08-01

    2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

  10. Effects of vitamin D binding protein-macrophage activating factor (DBP-MAF) infusion on bone resorption in two osteopetrotic mutations.

    PubMed

    Schneider, G B; Benis, K A; Flay, N W; Ireland, R A; Popoff, S N

    1995-06-01

    Osteopetrosis is a heterogeneous group of bone diseases characterized by an excess accumulation of bone and a variety of immune defects. Osteopetrosis (op) and incisors absent (ia) are two nonallelic mutations in the rat which demonstrated these skeletal defects as a result of reduced bone resorption. Osteopetrotic (op) rats have severe sclerosis as a result of reduced numbers of osteoclasts which are structurally abnormal. The sclerosis in ia rats is not as severe as in op mutants; they have elevated numbers of osteoclasts, but they are also morphologically abnormal, lacking a ruffled border. Both of these mutations have defects in the inflammation-primed activation of macrophages. They demonstrate independent defects in the cascade involved in the conversion of vitamin D binding protein (DBP) to a potent macrophage activating factor (DBP-MAF). Because this factor may also play a role in the pathogenesis of osteoclastic dysfunction, the effects of ex vivo-generated DBP-MAF were evaluated on the skeletal system of these two mutations. Newborn ia and op rats and normal littermate controls were injected with DBP-MAF or vehicle once every 4 days from birth until 2 weeks of age, at which time bone samples were collected to evaluate a number of skeletal parameters. DBP-MAF treated op rats had an increased number of osteoclasts and the majority of them exhibited normal structure. There was also reduced bone volume in the treated op animals and an associated increased cellularity of the marrow spaces. The skeletal sclerosis was also corrected in the ia rats; the bone marrow cavity size was significantly enlarged and the majority of the osteoclasts appeared normal with extensive ruffled borders. PMID:7669443

  11. Mononucleated Blood Cell Populations Display Different Abilities To Transmit Prion Disease by the Transfusion Route

    PubMed Central

    Douet, Jean-Yves; Lacroux, Caroline; Litaise, Claire; Lugan, Séverine; Corbière, Fabien; Arnold, Mark; Simmons, Hugh; Aron, Naima; Costes, Pierrette; Tillier, Cécile; Cassard, Hervé

    2016-01-01

    ABSTRACT Previous experiments carried out in a sheep scrapie model demonstrated that the transfusion of 200 μl of prion-infected whole blood has an apparent 100% efficacy for disease transmission. These experiments also indicated that, despite the apparent low infectious titer, the intravenous administration of white blood cells (WBC) resulted in efficient disease transmission. In the study presented here, using the same transmissible spongiform encephalopathy (TSE) animal model, our aim was to determine the minimal number of white blood cells and the specific abilities of mononucleated cell populations to transmit scrapie by the transfusion route. Our results confirmed that the transfusion of 100 μl, but not 10 μl, of fresh whole blood collected in asymptomatic scrapie-infected donor sheep can transmit the disease. The data also show that the intravenous administration of 105 WBCs is sufficient to cause scrapie in recipient sheep. Cell-sorted CD45R+ (predominantly B lymphocytes), CD4+/CD8+ (T lymphocytes), and CD14+ (monocytes/macrophages) blood cell subpopulations all were shown to contain prion infectivity by bioassays in ovine PrP transgenic mice. However, while the intravenous administration of 106 CD45+ or CD4+/8+ living cells was able to transmit the disease, similar numbers of CD14+ cells failed to infect the recipients. These data support the contention that mononucleated blood cell populations display different abilities to transmit TSE by the transfusion route. They also represent an important input for the risk assessment of blood-borne prion disease transmission and for refining the target performance of leukoreduction processes that currently are applied to mitigate the transmission risk in transfusion medicine. IMPORTANCE Interindividual variant Creutzfeldt-Jakob disease (vCJD) transmission through blood and blood-derived products is considered a major public health issue in transfusion medicine. Over the last decade, TSE in sheep has emerged as a

  12. Determination of the differentiation capacities of murines' primary mononucleated cells and MC3T3-E1 cells

    PubMed Central

    2010-01-01

    Background The main morphological features of primitive cells, such as stem and progenitor cells, are that these cells consists only one nucleus. The main purpose of this study was to determine the differentiation capacities of stem and progenitor cells. This study was performed using mononucleated cells originated from murine peripheral blood and MC3T3-E1 cells. Three approaches were used to determine their differentiation capacities: 1) Biochemical assays, 2) Gene expression analysis, and 3) Morphological observations. Results We found that both cells were able to differentiate into mature osteoblasts, as assayed by ALP activity. RT-PCR analysis showed the activation of the Opn gene after osteoblast differentiation. Morphological observations of both cells revealed the formation of black or dark-brown nodules after von Kossa staining. Nevertheless, only mononucleated cells showed the significant increase in TRAP activity characteristic of mature osteoclasts. The osteoclast-specific CatK gene was only upregulated in mononucleated cells. Morphological observations indicated the existence of multinucleated osteoclasts. Sca-1 was activated only in undifferentiated mononucleated cells, indicating that the cells were hematopoietic stem cells. In both cell lines, the housekeeping Gapdh gene was activated before and after differentiation. Conclusion The isolated mononucleated cells were able to differentiate into both osteoblasts and osteoclasts; indicating that they are stem cells. On the other hand, MC3T3-E1 cells can only differentiate into osteoblasts; a characteristic of progenitor cells. PMID:20979664

  13. Mechanisms of Bone Resorption in Periodontitis

    PubMed Central

    Hienz, Stefan A.; Paliwal, Sweta

    2015-01-01

    Alveolar bone loss is a hallmark of periodontitis progression and its prevention is a key clinical challenge in periodontal disease treatment. Bone destruction is mediated by the host immune and inflammatory response to the microbial challenge. However, the mechanisms by which the local immune response against periodontopathic bacteria disturbs the homeostatic balance of bone formation and resorption in favour of bone loss remain to be established. The osteoclast, the principal bone resorptive cell, differentiates from monocyte/macrophage precursors under the regulation of the critical cytokines macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin. TNF-α, IL-1, and PGE2 also promote osteoclast activity, particularly in states of inflammatory osteolysis such as those found in periodontitis. The pathogenic processes of destructive inflammatory periodontal diseases are instigated by subgingival plaque microflora and factors such as lipopolysaccharides derived from specific pathogens. These are propagated by host inflammatory and immune cell influences, and the activation of T and B cells initiates the adaptive immune response via regulation of the Th1-Th2-Th17 regulatory axis. In summary, Th1-type T lymphocytes, B cell macrophages, and neutrophils promote bone loss through upregulated production of proinflammatory mediators and activation of the RANK-L expression pathways. PMID:26065002

  14. CD44 Occupancy Prevents Macrophage Multinucleation

    PubMed Central

    Sterling, Hyacinth; Saginario, Charles; Vignery, Agnès

    1998-01-01

    Cells of the mononuclear phagocyte lineage have the capability to adhere to and fuse with each other and to differentiate into osteoclasts and giant cells. To investigate the macrophage adhesion/fusion mechanism, we focused our attention on CD44, a surface glycoprotein known to play a role in hematopoietic cell–cell adhesion. We report that CD44 expression by macrophages is highly and transiently induced by fusogenic conditions both in vitro and in vivo. We show that CD44 ligands, hyaluronic acid, chondroitin sulfates, and osteopontin prevent macrophage multinucleation. In addition, we report that the recombinant extracellular domain of CD44 binds fusing macrophages and prevents multinucleation in vitro. These data suggest that CD44 may control the mononucleated status of macrophages in tissues by virtue of mediating cell–cell interaction. PMID:9813101

  15. Tooth resorption part II - external resorption: Case series

    PubMed Central

    Fernandes, Marina; de Ataide, Ida; Wagle, Rahul

    2013-01-01

    External tooth resorption usually follows trauma to the periodontal ligament. It can be classified into five categories based on its clinical and histological manifestations. Calcium hydroxide has long been used as an intracanal medicament to slow down the resorption process due to its alkaline pH. A combination of both external and internal resorptions can also occur on the same tooth, making the management more complex. Five case reports of external resorption have been presented in this article along with pertinent review of literature. Successful management was possible in two cases, while extractions had to be advised in 3 cases due to advanced nature of the lesions. PMID:23716975

  16. Hypoxic regulation of osteoclast differentiation and bone resorption activity

    PubMed Central

    Knowles, Helen J

    2015-01-01

    Bone integrity is maintained throughout life via the homeostatic actions of bone cells, namely, osteoclasts, which resorb bone, and osteoblasts, which produce bone. Disruption of this balance in favor of osteoclast activation results in pathological bone loss, which occurs in conditions including osteoporosis, rheumatoid arthritis, primary bone cancer, and cancer metastasis to bone. Hypoxia also plays a major role in these conditions, where it is associated with disease progression and poor prognosis. In recent years, considerable interest has arisen in the mechanisms whereby hypoxia and the hypoxia-inducible transcription factors, HIF-1α and HIF-2α, affect bone remodeling and bone pathologies. This review summarizes the current evidence for hypoxia-mediated regulation of osteoclast differentiation and bone resorption activity. Role(s) of HIF and HIF target genes in the formation of multinucleated osteoclasts from cells of the monocyte–macrophage lineage and in the activation of bone resorption by mature osteoclasts will be discussed. Specific attention will be paid to hypoxic metabolism and generation of ATP by osteoclasts. Hypoxia-driven increases in both glycolytic flux and mitochondrial metabolic activity, along with consequent generation of mitochondrial reactive oxygen species, have been found to be essential for osteoclast formation and resorption activity. Finally, evidence for the use of HIF inhibitors as potential therapeutic agents targeting bone resorption in osteolytic disease will be discussed. PMID:27774484

  17. Invasive Cervical Resorption: A Review

    PubMed Central

    Kandalgaonkar, Shilpa D; Gharat, Leena A; Tupsakhare, Suyog D; Gabhane, Mahesh H

    2013-01-01

    Invasive cervical resorption is a relatively uncommon form of external root resorption exhibiting no external signs. The resorptive condition is often detected by routine radiographic examination. The clinical features vary from a small defect at the gingival margin to a pink coronal discoloration of the tooth crown resulting in ultimate cavitation of the overlying enamel which is painless unless pulpal or periodontal infection supervenes. Radiographic features of lesions vary from well-delineated to irregularly bordered mottled radiolucencies, and these can be confused with dental caries. A characteristic radiopaque line generally separates the image of the lesion from that of the root canal, because the pulp remains protected by a thin layer of predentin until late in the process. Histopathologically, the lesions contain fibrovascular tissue with resorbing clastic cells adjacent to the dentin surface. More advanced lesions display fibro-osseous characteristics with deposition of ectopic bonelike calcifications both within the resorbing tissue and directly on the dentin surface. How to cite this article: Kandalgaonkar SD, Gharat LA, Tupsakhare SD, Gabhane MH. Invasive Cervical Resorption: A Review. J Int Oral Health 2013;5(6):124-30 . PMID:24453457

  18. Micronuclei induced by reverse transcriptase inhibitors in mononucleated and binucleated cells as assessed by the cytokinesis-block micronucleus assay

    PubMed Central

    2010-01-01

    This study evaluated the clastogenic and/or aneugenic potential of three nucleoside reverse transcriptase inhibitors (zidovudine - AZT, lamivudine - 3TC and stavudine - d4T) using the cytokinesis-block micronucleus (CBMN) assay in human lymphocyte cultures. All three inhibitors produced a positive response when tested in binucleated cells. The genotoxicity of AZT and 3TC was restricted to binucleated cells since there was no significant increase in the frequency of micronuclei in mononucleated cells. This finding indicated that AZT and 3TC caused chromosomal breakage and that their genotoxicity was related to a clastogenic action. In addition to the positive response observed with d4T in binucleated cells, this drug also increased the frequency of micronuclei in mononucleated cells, indicating clastogenic and aneugenic actions. Since the structural differences between AZT and 3TC and AZT and d4T involve the 3' position in the 2'-deoxyribonucleoside and in an unsaturated 2',3',dideoxyribose, respectively, we suggest that an unsaturated 2', 3', dideoxyribose is responsible for the clastogenic and aneugenic actions of d4T. PMID:21637587

  19. Clinical technique for invasive cervical root resorption

    PubMed Central

    Silveira, Luiz Fernando Machado; Silveira, Carina Folgearini; Martos, Josué; Piovesan, Edno Moacir; César Neto, João Batista

    2011-01-01

    This clinical case report describes the diagnosis and treatment of an external invasive cervical resorption. A 17-year-old female patient had a confirmed diagnosis of invasive cervical resorption class 4 by cone beam computerized tomography. Although, there was no communication with the root canal, the invasive resorption process was extending into the cervical and middle third of the root. The treatment of the cervical resorption of the lateral incisor interrupted the resorptive process and restored the damaged root surface and the dental functions without any esthetic sequelae. Both the radiographic examination and computed tomography are imperative to reveal the extent of the defect in the differential diagnosis. PMID:22144822

  20. [Pharmacology of bone resorption inhibitor].

    PubMed

    Menuki, Kunitaka; Sakai, Akinori

    2015-10-01

    Currently, bone resorption inhibitor is mainly used for osteoporosis. A number of these agents have been developed. These pharmacological action are various. Bisphosphonate inhibit functions of the osteoclasts by inducing apoptosis. On the one hand, RANK-ligand inhibitor and selective estrogen receptor modulator inhibit formation of osteoclasts. It is important to understand these pharmacological action for the selection of the appropriate medicine. PMID:26529923

  1. Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources.

    PubMed

    Valerii, Maria Chiara; Ricci, Chiara; Spisni, Enzo; Di Silvestro, Raffaella; De Fazio, Luigia; Cavazza, Elena; Lanzini, Alberto; Campieri, Massimo; Dalpiaz, Alessandro; Pavan, Barbara; Volta, Umberto; Dinelli, Giovanni

    2015-06-01

    Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome whose triggering mechanisms remain unsettled. This study aimed to clarify how cultured peripheral blood mononucleated cells (PBMC) obtained from NCGS patients responded to contact with wheat proteins. Results demonstrated that wheat protein induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS patients, and that the overactivation level depends on the cereal source from which proteins are obtained. CXCL10 is able to decrease the transepithelial resistance of monolayers of normal colonocytes (NCM 460) by diminishing the mRNA expression of cadherin-1 (CDH1) and tight junction protein 2 (TJP2), two primary components of the tight junction strands. Thus, CXCL10 overactivation is one of the mechanisms triggered by wheat proteins in PBMC obtained from NCGS patients. This mechanism is activated to a greater extent by proteins from modern with respect to those extracted from ancient wheat genotypes.

  2. Detection of AIDS Virus in Macrophages in Brain Tissue from AIDS Patients with Encephalopathy

    NASA Astrophysics Data System (ADS)

    Koenig, Scott; Gendelman, Howard E.; Orenstein, Jan M.; Canto, Mauro C.; Pezeshkpour, Gholam H.; Yungbluth, Margaret; Janotta, Frank; Aksamit, Allen; Martin, Malcolm A.; Fauci, Anthony S.

    1986-09-01

    One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.

  3. COMPUTED TOMOGRAPHY OF TOOTH RESORPTION IN CATS.

    PubMed

    Lang, Linda G; Wilkinson, Thomas E; White, Tammy L; Farnsworth, Raelynn K; Potter, Kathleen A

    2016-09-01

    Tooth resorption is the most common dental disease in cats and can be a source of oral pain. The current clinical gold standard for diagnosis includes a combination of oral exam and dental radiography, however early lesions are not always detected. Computed tomography (CT) of the skull, including the dental arches, is a commonly performed diagnostic procedure, however the appearance of tooth resorption on CT and the diagnostic ability of CT to detect tooth resorption have not been evaluated. The purpose of this prospective, descriptive, diagnostic accuracy study was to characterize the CT appearance of tooth resorption in a sample of affected cats and to evaluate the sensitivity and specificity of CT for tooth resorption compared to the clinical gold standard of oral exam and intraoral dental radiography. Twenty-eight cat cadaver specimens were recruited for inclusion. Each specimen was evaluated using oral exam, intraoral dental radiography, and computed tomography (four different slice thicknesses). Each tooth was evaluated for the presence or absence of tooth resorption. Teeth with lesions and a subset of normal teeth were evaluated with histopathology. On CT, tooth resorption appeared as irregularly marginated hypoattenuating defects in the mineral attenuating tooth components, most commonly involving the root or cementoenamel junction. Sensitivity for CT detection of tooth resorption was fair to poor (42.2-57.7%) and specificity was good to excellent (92.8-96.3%). Findings from this study indicated that CT has high specificity but low sensitivity for detection of tooth resorption in cats.

  4. Resorption of monetite calcium phosphate cement by mouse bone marrow derived osteoclasts.

    PubMed

    Montazerolghaem, M; Karlsson Ott, M; Engqvist, H; Melhus, H; Rasmusson, A J

    2015-01-01

    Recently the interest for monetite based biomaterials as bone grafts has increased; since in vivo studies have demonstrated that they are degradable, osteoconductive and improve bone healing. So far osteoclastic resorption of monetite has received little attention. The current study focuses on the osteoclastic resorption of monetite cement using primary mouse bone marrow macrophages, which have the potential to differentiate into resorbing osteoclasts when treated with receptor activator NF-κB ligand (RANKL). The osteoclast viability and differentiation were analysed on monetite cement and compared to cortical bovine bone discs. After seven days live/dead stain results showed no significant difference in viability between the two materials. However, the differentiation was significantly higher on the bone discs, as shown by tartrate resistant acid phosphatase (TRAP) activity and Cathepsin K gene expression. Moreover monetite samples with differentiated osteoclasts had a 1.4 fold elevated calcium ion concentration in their culture media compared to monetite samples with undifferentiated cells. This indicates active resorption of monetite in the presence of osteoclasts. In conclusion, this study suggests that osteoclasts have a crucial role in the resorption of monetite based biomaterials. It also provides a useful model for studying in vitro resorption of acidic calcium phosphate cements by primary murine cells. PMID:25953560

  5. Skeletal muscle-melanocyte association during tadpole tail resorption in a tropical frog, Clinotarsus curtipes Jerdon (Anura, Ranoidea).

    PubMed

    Divya, Lekha; Beyo, Reston S; Sreejith, Parameswaran; Akbarsha, Mohammad A; Oommen, Oommen V

    2010-05-01

    We tested the hypothesis that melanin has a role as a molecule within the thyroid-mediated cascade. Light microscopic and ultrastructural changes in the skeletal muscle during tail resorption in tadpoles of the tropical frog Clinotarsus curtipes Jerdon (Anura: Ranoidea) were observed. Light microscopic analysis at metamorphic stage XVIII showed a melanized epidermis. A gradual migration of melanocytes from the epidermis to the dermis and filopodia of melanocytes pervading the skeletal muscle preceded tail resorption. The invasion of melanocytes into the muscle bundles coincided with the breakdown of the muscle bundles into sarcolytes and the arrival of macrophages at this site. This would suggest that the melanocyte-sarcolyte association signals the arrival of macrophages at these sites as metamorphosis progressed. Melanophages, macrophages with melanin granules, were observed at the climax stage of XXIII. The sarcolytes and the melanin granules were phagocytosed by macrophages so as to completely cleanse the exocytic muscle debris and the melanin granules. The presence of large melanomacrophage centers in the tadpole liver at metamorphic climax suggests that these phagocytic macrophages were further processed in the liver and, likely, in the spleen. It is proposed that melanin, a byzantine molecule, has a role in the cascade of events leading to tail resorption in anuran tadpoles.

  6. Apical root resorption in orthodontically treated adults.

    PubMed

    Baumrind, S; Korn, E L; Boyd, R L

    1996-09-01

    This study analyzed the relationship in orthodontically treated adults between upper central incisor displacement measured on lateral cephalograms and apical root resorption measured on anterior periapical x-ray films. A multiple linear regression examined incisor displacements in four directions (retraction, advancement, intrusion, and extrusion) as independent variables, attempting to account for observed differences in the dependent variable, resorption. Mean apical resorption was 1.36 mm (sd +/- 1.46, n = 73). Mean horizontal displacement of the apex was -0.83 mm (sd +/- 1.74, n = 67); mean vertical displacement was 0.19 mm (sd +/- 1.48, n = 67). The regression coefficients for the intercept and for retraction were highly significant; those for extrusion, intrusion, and advancement were not. At the 95% confidence level, an average of 0.99 mm (se = +/- 0.34) of resorption was implied in the absence of root displacement and an average of 0.49 mm (se = +/- 0.14) of resorption was implied per millimeter of retraction. R2 for all four directional displacement variables (DDVs) taken together was only 0.20, which implied that only a relatively small portion of the observed apical resorption could be accounted for by tooth displacement alone. In a secondary set of univariate analyses, the associations between apical resorption and each of 14 additional treatment-related variables were examined. Only Gender, Elapsed Time, and Total Apical Displacement displayed statistically significant associations with apical resorption. Additional multiple regressions were then performed in which the data for each of these three statistically significant variables were considered separately, with the data for the four directional displacement variables. The addition of information on Elapsed Time or Total Apical Displacement did not explain a significant additional portion of the variability in apical resorption. On the other hand, the addition of information on Gender to the

  7. Glucose-dependent insulinotropic polypeptide (GIP) dose-dependently reduces osteoclast differentiation and resorption.

    PubMed

    Mabilleau, Guillaume; Perrot, Rodolphe; Mieczkowska, Aleksandra; Boni, Sébastien; Flatt, Peter R; Irwin, Nigel; Chappard, Daniel

    2016-10-01

    A role for glucose-dependent insulinotropic polypeptide (GIP) in controlling bone resorption has been suspected. However uncertainty remains to identify whether GIP act directly on osteoclasts. The aim of the present study were (i) to identify in different osteoclast differentiation models (human peripheral blood mononuclear cells-PBMC, murine bone marrow macrophage-BMM and murine Raw 264.7 cells) whether GIP was capable of reducing osteoclast formation and resorption; (ii) ascertain whether the highly potent GIP analogue N-AcGIP was capable of inducing a response at lower concentrations and (iii) to decipher the molecular mechanisms responsible for such effects. [d-Ala(2)]-GIP dose-dependently reduced osteoclast formation at concentration as low as 1nM in human PBMC and 10nM in murine BMM cultures. Furthermore, [d-Ala(2)]-GIP also reduced the extent of osteoclast resorption at concentration as low as 1nM in human PBMC and murine BMM cultures. The mechanism of action of [d-Ala(2)]-GIP appeared to be mediated by reduction in intracellular calcium concentration and oscillation that subsequently inhibited calcineurin activity and NFATc1 nuclear translocation. The potency of the highly potent N-AcGIP was determined and highlighted an effect on osteoclast formation and resorption at concentration ten times lower than observed with [d-Ala(2)]-GIP in vitro. Furthermore, N-AcGIP was also capable of reducing the number of osteoclast in ovariectomized mice as well as the circulating level of type I collagen C-telopeptide. Pharmacological concentrations required for reducing osteoclast formation and resorption provide the impetus to design and exploit enzymatically stable GIP analogues for the treatment of bone resorption disorders in humans. PMID:27451082

  8. Sinusoidal electromagnetic fields promote bone formation and inhibit bone resorption in rat femoral tissues in vitro.

    PubMed

    Zhou, Jian; Ma, Xiao-Ni; Gao, Yu-Hai; Yan, Juan-Li; Shi, Wen-Gui; Xian, Cory J; Chen, Ke-Ming

    2016-01-01

    Effects of sinusoidal electromagnetic fields (SEMFs) on bone metabolism have not yet been well defined. The present study investigated SEMF effects on bone formation and resorption in rat femur bone tissues in vitro. Cultured femur diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues were treated with 50 Hz 1.8 mT SEMFs 1.5 h per day for up to 12 days and treatment effects on bone formation and resorption markers and associated gene expression were examined. Treatment with SEMFs caused a significant increase in alkaline phosphatase (ALP) activity and inhibited the tartrate-resistant acid phosphatase (TRACP) activity in the femoral diaphyseal or metaphyseal tissues. SEMFs also significantly increased levels of mRNA expression of osterix (OSX), insulin-like growth factor (IGF-1) and ALP in the bone tissues. SEMF treatment decreased glucose content and increased lactic acid contents in the culture conditioned medium. In addition, treatment with SEMFs decreased mRNA expression levels of bone resorption-related genes TRACP, macrophage colony stimulating factor (M-CSF) and cathepsin K (CTSK) in the cultured bone tissues. In conclusion, the current study demonstrated that treatment with 1.8 mT SEMFs at 1.5 h per day promoted bone formation, increased metabolism and inhibited resorption in both metaphyseal and diaphyseal bone tissues in vitro.

  9. Thyroxine Induced Resorption of Xenopus Laevis Tail Tissue in Vitro.

    ERIC Educational Resources Information Center

    Scadding, Steven R.

    1984-01-01

    A simple method of studying thyroxine-induced resorption of tadpole tails in vitro is described. This procedure demonstrates that resorption is dependent on thyroxine and requires protein synthesis. It introduces students to the use of tissue culture methods. (Author)

  10. Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

    PubMed

    Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

    2014-09-01

    Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity

  11. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy

    PubMed Central

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  12. Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy.

    PubMed

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2015-01-01

    We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. PMID:26137498

  13. [Calcitonin as an alternative treatment for root resorption].

    PubMed

    Pierce, A; Berg, J O; Lindskog, S

    1989-01-01

    Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption.

  14. [Calcitonin as an alternative treatment for root resorption].

    PubMed

    Pierce, A; Berg, J O; Lindskog, S

    1989-01-01

    Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption. PMID:2576918

  15. Stoichiometric patterns in foliar nutrient resorption across multiple scales

    USGS Publications Warehouse

    Reed, Sasha C.; Townsend, Alan R.; Davidson, Eric A.; Cleveland, Cory C.

    2012-01-01

    *Nutrient resorption is a fundamental process through which plants withdraw nutrients from leaves before abscission. Nutrient resorption patterns have the potential to reflect gradients in plant nutrient limitation and to affect a suite of terrestrial ecosystem functions. *Here, we used a stoichiometric approach to assess patterns in foliar resorption at a variety of scales, specifically exploring how N : P resorption ratios relate to presumed variation in N and/or P limitation and possible relationships between N : P resorption ratios and soil nutrient availability. *N : P resorption ratios varied significantly at the global scale, increasing with latitude and decreasing with mean annual temperature and precipitation. In general, tropical sites (absolute latitudes < 23°26′) had N : P resorption ratios of < 1, and plants growing on highly weathered tropical soils maintained the lowest N : P resorption ratios. Resorption ratios also varied with forest age along an Amazonian forest regeneration chronosequence and among species in a diverse Costa Rican rain forest. *These results suggest that variations in N : P resorption stoichiometry offer insight into nutrient cycling and limitation at a variety of spatial scales, complementing other metrics of plant nutrient biogeochemistry. The extent to which the stoichiometric flexibility of resorption will help regulate terrestrial responses to global change merits further investigation.

  16. Etiology and sequelae of root resorption.

    PubMed

    Vlaskalic, V; Boyd, R L; Baumrind, S

    1998-06-01

    This article reviews the current status of investigation into apical root resorption within the context of orthodontic treatment. Treatment and patient factors that have traditionally been investigated are discussed, along with the results of current research in this area. The need for rethinking traditional research strategies in the quest for identifying both control and causative mechanisms is explored. Finally, proposals for key areas of future interest are highlighted.

  17. Bone resorption in chronic otitis media.

    PubMed

    Maynard, J; Bumsted, R M; Huang, C C; Abramson, M

    1979-01-01

    Bone resorption is an important aspect of chronic otitis media contributing to many complications of this disease. It is postulated that the mechanism of this localized destructive process is chemical in origin. Collagenase, lysosomal enzymes, prostaglandins, and other cell mediators are thought to induce bone resorption, but the site of action and cellular origin of these substances remains unclear. In this report, we demonstrate the location and attempt to delineate the cellular origin of two enzymes, collagenase and the lysosomal enzyme acid phosphatase in guinea pig temporal bones and human ossicles from ears containing chronic otitis media. Tissue localization of these enzymes identifies sites of active bone resorption and demonstrates the cells initiating this process. Using immunohistochemical and immunocytochemical techniques, collagenase was seen surrounding mononuclear inflammatory cells of granulation tissue at bone resorbing margins and at the periphery of osteocyte lacunae adjacent to resorbing areas. Electron microscopic data suggests that collagenase is an extracellular enzyme foun at the periphery of osteocytes. In addition, abundant acid phosphatase activity was seen in the same cells that exhibited collagenase staining, lending credence to the destructive function of these cells. The chronic inflammatory reaction found in chronic otitis media appears to activate bone destruction through the dynamic activity of mononuclear inflammatory cells and stimulates bone cells to increase their destructive biochemical functions.

  18. Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL

    PubMed Central

    Kassem, Ali; Lindholm, Catharina; Lerner, Ulf H

    2016-01-01

    Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S

  19. Progressive condylar resorption after mandibular advancement.

    PubMed

    Kobayashi, Tadaharu; Izumi, Naoya; Kojima, Taku; Sakagami, Naoko; Saito, Isao; Saito, Chikara

    2012-03-01

    Progressive condylar resorption is an irreversible complication and a factor in the development of late skeletal relapse after orthognathic surgery. We have evaluated cephalometric characteristics, signs and symptoms in the temporomandibular joint (TMJ), and surgical factors in six patients (one man and five women) who developed it after orthognathic surgery. The findings in preoperative cephalograms indicated that the patients had clockwise rotation of the mandible and retrognathism because of a small SNB angle, a wide mandibular plane angle, and a "minus" value for inclination of the ramus. There were erosions or deformities of the condyles, or both, on three-dimensional computed tomography (CT) taken before treatment. The mean (SD) anterior movement of the mandible at operation was 12.1 (3.9)mm and the mean relapse was -6.4 (2.5)mm. The mean change in posterior facial height was 4.5 (2.1)mm at operation and the mean relapse was -5.3 (1.8)mm. Two patients had click, or pain, or both, preoperatively. The click disappeared in one patient postoperatively, but one of the patients who had been symptom-free developed crepitus postoperatively. In the classified resorption pattern, posterior-superior bone loss was seen in three cases, anterior-superior bone loss in two, and superior bone loss in one. Progressive condylar resorption after orthognathic surgery is multifactorial, and some of the risk factors are inter-related. Patients with clockwise rotation of the mandible and retrognathism in preoperative cephalograms; erosion, or deformity of the condyle, or both, on preoperative CT; and wide mandibular advancement and counterclockwise rotation of the mandibular proximal segment at operation, seemed to be at risk. The mandible should therefore be advanced only when the condyles are stable on radiographs, and careful attention should be paid to postoperative mechanical loading on the TMJ in high-risk patients. PMID:21440343

  20. Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases.

    PubMed

    Bhatia, Shannu K; Hunter, M Lindsay; Ashley, Paul F

    2015-12-01

    Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically.

  1. Hypergravity suppresses bone resorption in ovariectomized rats

    NASA Astrophysics Data System (ADS)

    Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2011-04-01

    The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

  2. Tooth resorption in the Swedish Eurasion lynx (Lynx lynx).

    PubMed

    Pettersson, Ann

    2010-01-01

    The etiology of tooth resorption in the domestic cat remains unknown. The high prevalence and progressive nature of the disease complicates defining healthy control groups. In order to evaluate the possible influence of various life style changes on the prevalence of tooth resorption, healthy control groups are a prerequisite. This paper presents a prevalence study for tooth resorption in a free-ranging wild felidae population. Skulls from 46 free-ranging Eurasian lynx (Lynx lynx) were examined. The age of the animals had previously been estimated based on cementum annuli in the maxillary right canine tooth. The dental examination included both dental probing and radiographic imaging. Complicated fractures of the canine teeth were found in 9/46 (19.5%) skulls. In one fractured canine, apical root resorption and periapical lucency was detected. The root resorption was attributed to inflammatory resorption as a consequence of the initial dental trauma and necrotic pulp. No signs of tooth resorption were found in the remaining teeth. Supernumerary roots were detected in 18/46 skulls (39.1 %). Supernumerary "peg" teeth caudal to the mandibular first molar tooth were detected in 6/46 (13.0%) skulls. Although further studies on dental ultra-structure are needed, the Swedish Eurasian lynx may, in the future, be useful as a healthy comparative model for studies on the etiopathogenesis of tooth resorption in the domestic cat. PMID:21322429

  3. Tooth resorption in the Swedish Eurasion lynx (Lynx lynx).

    PubMed

    Pettersson, Ann

    2010-01-01

    The etiology of tooth resorption in the domestic cat remains unknown. The high prevalence and progressive nature of the disease complicates defining healthy control groups. In order to evaluate the possible influence of various life style changes on the prevalence of tooth resorption, healthy control groups are a prerequisite. This paper presents a prevalence study for tooth resorption in a free-ranging wild felidae population. Skulls from 46 free-ranging Eurasian lynx (Lynx lynx) were examined. The age of the animals had previously been estimated based on cementum annuli in the maxillary right canine tooth. The dental examination included both dental probing and radiographic imaging. Complicated fractures of the canine teeth were found in 9/46 (19.5%) skulls. In one fractured canine, apical root resorption and periapical lucency was detected. The root resorption was attributed to inflammatory resorption as a consequence of the initial dental trauma and necrotic pulp. No signs of tooth resorption were found in the remaining teeth. Supernumerary roots were detected in 18/46 skulls (39.1 %). Supernumerary "peg" teeth caudal to the mandibular first molar tooth were detected in 6/46 (13.0%) skulls. Although further studies on dental ultra-structure are needed, the Swedish Eurasian lynx may, in the future, be useful as a healthy comparative model for studies on the etiopathogenesis of tooth resorption in the domestic cat.

  4. Histological and Immunohistochemical Evaluation of Autologous Cultured Bone Marrow Mesenchymal Stem Cells and Bone Marrow Mononucleated Cells in Collagenase-Induced Tendinitis of Equine Superficial Digital Flexor Tendon

    PubMed Central

    Crovace, Antonio; Lacitignola, Luca; Rossi, Giacomo; Francioso, Edda

    2010-01-01

    The aim of this study was to compare treatment with cultured bone marrow stromal cells (cBMSCs), bone marrow Mononucleated Cells (BMMNCs), and placebo to repair collagenase-induced tendinitis in horses. In six adult Standardbred horses, 4000 IU of collagenase were injected in the superficial digital flexor tendon (SDFT). Three weeks after collagenase treatment, an average of either 5.5 × 106 cBMSCs or 1.2 × 108 BMMNCs, fibrin glue, and saline solution was injected intralesionally in random order. In cBMSC- and BMMNCS-treated tendons, a high expression of cartilage oligomeric matrix protein (COMP) and type I collagen, but low levels of type III collagen were revealed by immunohistochemistry, with a normal longitudinally oriented fiber pattern. Placebo-treated tendons expressed very low quantities of COMP and type I collagen but large numbers of randomly oriented type III collagen fibers. Both cBMSC and BMMNCS grafts resulted in a qualitatively similar heling improvement of tendon extracellular matrix, in terms of the type I/III collagen ratio, fiber orientation, and COMP expression. PMID:20445779

  5. Peptidomimetic antagonists of alphavbeta3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone.

    PubMed

    Carron, C P; Meyer, D M; Engleman, V W; Rico, J G; Ruminski, P G; Ornberg, R L; Westlin, W F; Nickols, G A

    2000-06-01

    Osteoclasts are actively motile on bone surfaces and undergo alternating cycles of migration and resorption. Osteoclast interaction with the extracellular matrix plays a key role in the osteoclast resorptive process and a substantial body of evidence suggests that integrin receptors are important in osteoclast function. These integrin receptors bind to the Arg-Gly-Asp (RGD) sequence found in a variety of extracellular matrix proteins and it is well established that the interaction of osteoclast alpha v beta 3 integrin with the RGD motif within bone matrix proteins is important in osteoclast-mediated bone resorption. In this study, we characterized the effects of two synthetic peptidomimetic antagonists of alpha v beta 3, SC-56631 and SC-65811, on rabbit osteoclast adhesion to purified matrix proteins and bone, and on bone resorption in vitro. SC-56631 and SC-65811 are potent inhibitors of vitronectin binding to purified alpha v beta 3. Both SC-56631 and SC-65811 inhibited osteoclast adhesion to osteopontin- and vitronectin-coated surfaces and time-lapse video microscopy showed that osteoclasts rapidly retract from osteopontin-coated surfaces when exposed to SC-56631 and SC-65811. SC-56631 and SC-65811 blocked osteoclast-mediated bone resorption in a dose-responsive manner. Further analysis showed that SC-65811 and SC-56631 reduced the number of resorption pits produced per osteoclast and the average pit size. SC-65811 was a more potent inhibitor of bone resorption and the combination of reduced pit number and size led to a 90% inhibition of bone resorption. Surprisingly, however, osteoclasts treated with SC-65811, SC-56631 or the disintegrin echistatin, at concentrations that inhibit bone resorption did not inhibit osteoclast adhesion to bone. These results suggest that alphavbeta3 antagonists inhibited bone resorption by decreasing osteoclast bone resorptive activity or efficiency but not by inhibiting osteoclast adhesion to bone per se.

  6. Quantification of Condylar Resorption in TMJ Osteoarthritis

    PubMed Central

    Cevidanes, LHS; Hajati, A-K; Paniagua, B; Lim, PF; Walker, DG; Palconet, G; Nackley, AG; Styner, M; Ludlow, JB; Zhu, H; Phillips, C

    2010-01-01

    OBJECTIVE This study was performed to determine the condylar morphological variation of osteoarthritic (OA) and asymptomatic temporomandibular joints (TMJ) and to determine its correlation with pain intensity and duration. STUDY DESIGN Three dimensional surface models of mandibular condyles were constructed from Cone-Beam CT images of 29 female patients with TMJ OA (Research Diagnostic Criteria for Temporomandibular Disorders Group III) and 36 female asymptomatic subjects. Shape Correspondence was used to localize and quantify the condylar morphology. Statistical analysis was performed with MANCOVA analysis using Hotelling T2 metric based on covariance matrices, and Pearson correlation. RESULTS OA condylar morphology was statistically significantly different from the asymptomatic condyles (p<0.05). 3D morphological variation of the OA condyles was significantly correlated with pain intensity and duration. CONCLUSION 3D quantification of condylar morphology revealed profound differences between OA and asymptomatic condyles and the extent of the resorptive changes paralleled pain severity and duration. PMID:20382043

  7. [Resorption of hydrocyanic acid from linseed].

    PubMed

    Schulz, V; Löffler, A; Gheorghiu, T

    1983-01-01

    Resorption of hydrocyanic acid after ingestion of linseed was investigated in 20 healthy volunteers and 5 patients. The persons investigated took a single dose of 30 g or of 100 g of linseed or they received throughout several weeks 15 g. t.i.d. One volunteer also took for purposes of comparison bitter almonds or potassium cyanide. Before, during and after the periods of ingestion plasma levels of hydrocyanic acid and of thiocyanate were normal. During long-term trials urinary excretion of thiocyanate was monitored regularly. Intake of linseed even in extremely high dosages never caused significant rises of plasma thiocyanate levels; this, however, was the case after intake of bitter almonds or potassium cyanide. Thus, it can be excluded, that intoxication by hydrocyanic acid can be caused by linseed. Long-term intake of linseed however, raised plasma levels of thiocyanate significantly; at the same time urinary excretion of thiocyanate increased. PMID:6302421

  8. [Resorption of hydrocyanic acid from linseed].

    PubMed

    Schulz, V; Löffler, A; Gheorghiu, T

    1983-01-01

    Resorption of hydrocyanic acid after ingestion of linseed was investigated in 20 healthy volunteers and 5 patients. The persons investigated took a single dose of 30 g or of 100 g of linseed or they received throughout several weeks 15 g. t.i.d. One volunteer also took for purposes of comparison bitter almonds or potassium cyanide. Before, during and after the periods of ingestion plasma levels of hydrocyanic acid and of thiocyanate were normal. During long-term trials urinary excretion of thiocyanate was monitored regularly. Intake of linseed even in extremely high dosages never caused significant rises of plasma thiocyanate levels; this, however, was the case after intake of bitter almonds or potassium cyanide. Thus, it can be excluded, that intoxication by hydrocyanic acid can be caused by linseed. Long-term intake of linseed however, raised plasma levels of thiocyanate significantly; at the same time urinary excretion of thiocyanate increased.

  9. Clinical Management of Two Root Resorption Cases in Endodontic Practice.

    PubMed

    Mincik, Jozef; Urban, Daniel; Timkova, Silvia

    2016-01-01

    Root resorption is a pathological process involving loss of hard dental tissues. It may occur as a consequence of dental trauma, orthodontic treatment, and bleaching, and occasionally it accompanies periodontal disease. Although the mechanism of resorption process is examined in detail, its etiology is not fully understood. Wide open apical foramen is more difficult to manage and the root canal may often overfill. In this report we present two cases of root resorption and describe means for its clinical management. We conclude that useful measure of a success or failure in managing root resorption is the persistence of the resorption process. It is a clear sign of an active ongoing inflammatory process and shows the clinical need for retreatment. PMID:27648314

  10. Invasive cervical root resorption: Engineering the lost tissue by regeneration

    PubMed Central

    Johns, Dexton Antony; Shivashankar, Vasundara Yayathi; Maroli, Ramesh Kumar; Joseph, Rosamma

    2013-01-01

    Invasive cervical resorption (ICR) is a localized resorptive process that commences on the surface of the root below the epithelial attachment and the coronal aspect of the supporting alveolar process, namely the zone of the connective tissue attachment’ early diagnosis, elimination of the resorption and restorative management are the keys to a successful outcome. Treatment done was a combined non-surgical root canal therapy, surgical treatment to expose the resorptive defect and the resorptive defect was filled up with reverse sandwich technique and finally the bony defect filled with platelet rich fibrin (PRF), hydroxylapatite and PRF membrane. Significant bone fill was obtained in our case after a 2 year follow-up period. This case report presents a treatment strategy that might improve the healing outcomes for patients with ICR. PMID:24403805

  11. Clinical Management of Two Root Resorption Cases in Endodontic Practice

    PubMed Central

    2016-01-01

    Root resorption is a pathological process involving loss of hard dental tissues. It may occur as a consequence of dental trauma, orthodontic treatment, and bleaching, and occasionally it accompanies periodontal disease. Although the mechanism of resorption process is examined in detail, its etiology is not fully understood. Wide open apical foramen is more difficult to manage and the root canal may often overfill. In this report we present two cases of root resorption and describe means for its clinical management. We conclude that useful measure of a success or failure in managing root resorption is the persistence of the resorption process. It is a clear sign of an active ongoing inflammatory process and shows the clinical need for retreatment. PMID:27648314

  12. Clinical Management of Two Root Resorption Cases in Endodontic Practice

    PubMed Central

    2016-01-01

    Root resorption is a pathological process involving loss of hard dental tissues. It may occur as a consequence of dental trauma, orthodontic treatment, and bleaching, and occasionally it accompanies periodontal disease. Although the mechanism of resorption process is examined in detail, its etiology is not fully understood. Wide open apical foramen is more difficult to manage and the root canal may often overfill. In this report we present two cases of root resorption and describe means for its clinical management. We conclude that useful measure of a success or failure in managing root resorption is the persistence of the resorption process. It is a clear sign of an active ongoing inflammatory process and shows the clinical need for retreatment.

  13. Homegrown Macrophages.

    PubMed

    Kim, Ki-Wook; Zhang, Nan; Choi, Kyunghee; Randolph, Gwendalyn J

    2016-09-20

    Macrophages residing in different organs have diverse gene-expression programs. Mass et al. (2016) propose that this diversity develops "at home"-within those organs-after the recruitment of a common precursor that had not made prior commitments to diversity. PMID:27653599

  14. Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

    PubMed

    Petrova, Nina L; Petrov, Peter K; Edmonds, Michael E; Shanahan, Catherine M

    2014-04-01

    We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17. Resorption was measured at day 21 after toluidine blue staining by two methods: (1) area of resorption at the surface by image analysis (%) and (2) area of resorption under the surface (μm(2)) measured by a Dektak 150 Surface Profiler. Ten 1,000 μm-long scans were performed per disc. Pits were classified as unidented, bidented, and multidented according to their shape. Although the number of newly formed TRAcP positive multinucleated cells (>3 nuclei) was similar in M-CSF + RANKL-treated cultures between controls and Charcot patients, the latter exhibited increased resorbing activity. The area of resorption on the surface by image analysis was significantly greater in Charcot patients compared with controls (21.1 % [14.5-26.2] vs. 40.8 % [35.4-46.0], median [25-75th percentile], p < 0.01), as was the area of resorption under the surface (2.7 x 10(3) μm(2) [1.6 x 10(3)- 3.9 x 10(3)] vs. 8.3 x 10(3) μm (2) [5.6 x 10(3)- 10.6 x 10(3), [corrected] p < 0.01) after profilometry. In Charcot patients pits were deeper and wider and more frequently presented as multidented pits. This application of the Dektak 150 Surface Profiler revealed novel differences in resorption pit profile from osteoclasts derived from Charcot patients compared with controls. Resorption in Charcot patients was mediated by highly aggressive newly formed osteoclasts from monocytes eroding large and deep areas of bone. PMID:24322885

  15. Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation.

    PubMed

    Park-Min, Kyung-Hyun; Lim, Elisha; Lee, Min Joon; Park, Sung Ho; Giannopoulou, Eugenia; Yarilina, Anna; van der Meulen, Marjolein; Zhao, Baohong; Smithers, Nicholas; Witherington, Jason; Lee, Kevin; Tak, Paul P; Prinjha, Rab K; Ivashkiv, Lionel B

    2014-11-13

    Emerging evidence suggests that RANKL-induced changes in chromatin state are important for osteoclastogenesis, but these epigenetic mechanisms are not well understood and have not been therapeutically targeted. In this study, we find that the small molecule I-BET151 that targets bromo and extra-terminal (BET) proteins that 'read' chromatin states by binding to acetylated histones strongly suppresses osteoclastogenesis. I-BET151 suppresses pathologic bone loss in TNF-induced inflammatory osteolysis, inflammatory arthritis and post-ovariectomy models. Transcriptome analysis identifies a MYC-NFAT axis important for osteoclastogenesis. Mechanistically, I-BET151 inhibits expression of the master osteoclast regulator NFATC1 by suppressing expression and recruitment of its newly identified upstream regulator MYC. MYC is elevated in rheumatoid arthritis macrophages and its induction by RANKL is important for osteoclastogenesis and TNF-induced bone resorption. These findings highlight the importance of an I-BET151-inhibited MYC-NFAT axis in osteoclastogenesis, and suggest targeting epigenetic chromatin regulators holds promise for treatment of inflammatory and oestrogen deficiency-mediated pathologic bone resorption.

  16. The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption.

    PubMed

    Wu, Wei-Jie; Kim, Min Seuk; Ahn, Byung-Yong

    2015-10-01

    To further understand the correlation between vitamin K and bone metabolism, the effects of vitamins K1, menaquinone-4 (MK-4), and menaquinone-7 (MK-7) on RANKL-induced osteoclast differentiation and bone resorption were comparatively investigated. Vitamin K2 groups (MK-4 and MK-7) were found to significantly inhibit RANKL-medicated osteoclast cell formation of bone marrow macrophages (BMMs) in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of specific osteoclast differentiation markers, such as c-Fos, NFATc1, OSCAR, and TRAP, as well as NFATc1 protein expression and TRAP activity in RANKL-treated BMMs were inhibited by vitamin K2, although MK-4 exhibited a significantly greater efficiency compared to MK-7. In contrast, the same dose of vitamin K1 had no inhibitory effect on RANKL-induced osteoclast cell formation, but increased the expression of major osteoclastogenic genes. Interestingly, vitamins K1, MK-4 and MK-7 all strongly inhibited osteoclastic bone resorption (p < 0.01) in a dose dependent manner. These results suggest that vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.

  17. Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation.

    PubMed

    Park-Min, Kyung-Hyun; Lim, Elisha; Lee, Min Joon; Park, Sung Ho; Giannopoulou, Eugenia; Yarilina, Anna; van der Meulen, Marjolein; Zhao, Baohong; Smithers, Nicholas; Witherington, Jason; Lee, Kevin; Tak, Paul P; Prinjha, Rab K; Ivashkiv, Lionel B

    2014-01-01

    Emerging evidence suggests that RANKL-induced changes in chromatin state are important for osteoclastogenesis, but these epigenetic mechanisms are not well understood and have not been therapeutically targeted. In this study, we find that the small molecule I-BET151 that targets bromo and extra-terminal (BET) proteins that 'read' chromatin states by binding to acetylated histones strongly suppresses osteoclastogenesis. I-BET151 suppresses pathologic bone loss in TNF-induced inflammatory osteolysis, inflammatory arthritis and post-ovariectomy models. Transcriptome analysis identifies a MYC-NFAT axis important for osteoclastogenesis. Mechanistically, I-BET151 inhibits expression of the master osteoclast regulator NFATC1 by suppressing expression and recruitment of its newly identified upstream regulator MYC. MYC is elevated in rheumatoid arthritis macrophages and its induction by RANKL is important for osteoclastogenesis and TNF-induced bone resorption. These findings highlight the importance of an I-BET151-inhibited MYC-NFAT axis in osteoclastogenesis, and suggest targeting epigenetic chromatin regulators holds promise for treatment of inflammatory and oestrogen deficiency-mediated pathologic bone resorption. PMID:25391636

  18. Bortezomib Inhibits Osteoclastogenesis and Porphyromonas gingivalis Lipopolysaccharide-induced Alveolar Bone Resorption.

    PubMed

    Kim, Y-G; Kang, J H; Kim, H J; Kim, H J; Kim, H-H; Kim, J-Y; Lee, Y

    2015-09-01

    Healthy bone is maintained by the coordinated activities of osteoblast-mediated bone formation and osteoclast-dependent bone resorption. Pathologic conditions such as hormonal imbalance and inflammation cause increased osteoclastogenesis resulting in osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is novel antimyeloma agent that has a direct beneficial effect on bone formation. However, the role of bortezomib in osteoclastogenesis and underlying mechanisms remains to be fully comprehended. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)- and lipopolysaccharide-dependent osteoclast differentiation. Interestingly, the bortezomib-mediated inhibition of osteoclastogenesis was transient, since the removal of bortezomib from culture completely restored osteoclast differentiation. Bortezomib impeded the induction and nuclear localization of nuclear factor of activated T cells, cytoplasmic 1 and reduced both macrophage colony-stimulating factor- and RANKL-induced extracellular-signal-regulated kinase (ERK) phosphorylation. In a mouse model of periodontitis, bortezomib prevented alveolar bone erosion induced by Porphyromonas gingivalis lipopolysaccharide. These data not only suggest a previously unappreciated mechanism by which bortezomib regulates bone resorption but also propose novel applications of bortezomib beyond its use as an antimyeloma agent.

  19. Multiple idiopathic external apical root resorption: A rare case report

    PubMed Central

    Bansal, Parul; Nikhil, Vineeta; Kapur, Sonali

    2015-01-01

    Multiple idiopathic external apical root resorption (MIEARR) is a relatively rare condition affecting multiple teeth in a dentition. As the condition is nonsymptomatic, a case is usually detected as an incidental radiographic finding. However, it may cause pain and mobility in severe cases. It is sometimes self-limiting or sometimes may progress to tooth loss. This paper presents a case of external apical root resorption involving multiple teeth in which etiology was not identified, so idiopathic root resorption was considered as a diagnosis of exclusion. PMID:25657532

  20. Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation.

    PubMed

    Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

    2016-01-01

    Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclast-specific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β-induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss.

  1. Pathogen infection drives patterns of nutrient resorption in citrus plants

    PubMed Central

    Cao, Jirong; Cheng, Chunzhen; Yang, Junjie; Wang, Qibing

    2015-01-01

    Nutrient resorption processes in the plants infected by pathogen remain poorly understood. Huanglongbing (HLB) is a destructive disease of citrus. HLB-pathogen ‘Candidatus Liberibacter asiaticus’ grows specifically in the phloem of hosts and may cause problems in the plant vascular system after infection. Therefore, it brings a great concern about the phloem nutrient transport and nutrient intra-cycling in HLB-affected plants. We investigated the effects of ‘Ca. L. asiaticus’ infection on nitrogen (N) and phosphorus (P) concentrations and resorption in different citrus species (i.e. Citrus reticulata, Citrus limon and Citrus maxima). HLB-pathogen infection had distinctive impacts on nutrient resorption in different species. P resorption efficiency substantially decreased in infected C. reticulata plants relative to the healthy plants in summer, which may account for the marked decrease in the average fruit yield. P resorption was more efficient in infected C. limon plants than in the healthy plants. However, for C. maxima plants, HLB had no significant effects on N:P ratio in live leaves and resorption efficiency as well as on fruit yield. Keeping efficient internal nutrient cycling can be a strategy of citrus species being tolerant to HLB. PMID:26419510

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

    PubMed Central

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

    2015-01-01

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

  3. Pathogen infection drives patterns of nutrient resorption in citrus plants.

    PubMed

    Cao, Jirong; Cheng, Chunzhen; Yang, Junjie; Wang, Qibing

    2015-01-01

    Nutrient resorption processes in the plants infected by pathogen remain poorly understood. Huanglongbing (HLB) is a destructive disease of citrus. HLB-pathogen 'Candidatus Liberibacter asiaticus' grows specifically in the phloem of hosts and may cause problems in the plant vascular system after infection. Therefore, it brings a great concern about the phloem nutrient transport and nutrient intra-cycling in HLB-affected plants. We investigated the effects of 'Ca. L. asiaticus' infection on nitrogen (N) and phosphorus (P) concentrations and resorption in different citrus species (i.e. Citrus reticulata, Citrus limon and Citrus maxima). HLB-pathogen infection had distinctive impacts on nutrient resorption in different species. P resorption efficiency substantially decreased in infected C. reticulata plants relative to the healthy plants in summer, which may account for the marked decrease in the average fruit yield. P resorption was more efficient in infected C. limon plants than in the healthy plants. However, for C. maxima plants, HLB had no significant effects on N:P ratio in live leaves and resorption efficiency as well as on fruit yield. Keeping efficient internal nutrient cycling can be a strategy of citrus species being tolerant to HLB. PMID:26419510

  4. Pathogen infection drives patterns of nutrient resorption in citrus plants.

    PubMed

    Cao, Jirong; Cheng, Chunzhen; Yang, Junjie; Wang, Qibing

    2015-09-30

    Nutrient resorption processes in the plants infected by pathogen remain poorly understood. Huanglongbing (HLB) is a destructive disease of citrus. HLB-pathogen 'Candidatus Liberibacter asiaticus' grows specifically in the phloem of hosts and may cause problems in the plant vascular system after infection. Therefore, it brings a great concern about the phloem nutrient transport and nutrient intra-cycling in HLB-affected plants. We investigated the effects of 'Ca. L. asiaticus' infection on nitrogen (N) and phosphorus (P) concentrations and resorption in different citrus species (i.e. Citrus reticulata, Citrus limon and Citrus maxima). HLB-pathogen infection had distinctive impacts on nutrient resorption in different species. P resorption efficiency substantially decreased in infected C. reticulata plants relative to the healthy plants in summer, which may account for the marked decrease in the average fruit yield. P resorption was more efficient in infected C. limon plants than in the healthy plants. However, for C. maxima plants, HLB had no significant effects on N:P ratio in live leaves and resorption efficiency as well as on fruit yield. Keeping efficient internal nutrient cycling can be a strategy of citrus species being tolerant to HLB.

  5. The RhoGAP Activity of Myosin IXB Is Critical for Osteoclast Podosome Patterning, Motility, and Resorptive Capacity

    PubMed Central

    McMichael, Brooke K.; Scherer, Katharine F.; Franklin, Nicole C.; Lee, Beth S.

    2014-01-01

    Osteoclasts are large, multinucleated cells of the monocyte-macrophage lineage that generate specialized substrate adhesion complexes to facilitate their function as bone-degrading cells. The patterning and function of these actin-based complexes, podosomes and sealing zones, are regulated by the small GTPase Rho. Myosin IXB (Myo9b) is a unique actin-based motor protein that contains a RhoGAP domain, which, like other RhoGAPs, is inhibitory to Rho signaling. In this study, Myo9b is shown to be expressed in osteoclasts and act as a critical regulator of podosome patterning and osteoclast function. SiRNA-mediated knockdown of Myo9b results in increased activity of Rho but not Rac in osteoclasts. Knockdown in osteoclasts on glass results in altered podosome patterning and decreased motility, and this effect is reversed by addition of a Rho inhibitor. SiRNA-mediated suppression of Myo9b expression in osteoclasts on bone results in a dramatic loss of resorptive capacity even though sealing zones appear normal. This loss of resorption is also reversible with addition of a Rho inhibitor. Cells with diminished Myo9b levels display mislocalization and suppressed activation of Src, a tyrosine kinase with critical effects on osteoclast actin cytoskeletal rearrangement and function. In addition, siRNA-treated cells display poorly formed microtubule networks and a lack of tubulin acetylation, a marker of microtubule stability. However, short-term addition of TNFα to cells with suppressed Myo9b levels overcomes or circumvents these defects and causes increased sealing zone size and resorptive capacity. These results indicate that the RhoGAP activity of Myo9b plays a key role in regulating the actin-based structures necessary for osteoclast motility and resorption, and confirms that Myo9b can act as a motorized signaling molecule that links Rho signaling to the dynamic actin cytoskeleton. PMID:24466350

  6. The fundamental role of increased production of nitric oxide in lipopolysaccharide-induced embryonic resorption in mice.

    PubMed

    Ogando, D G; Paz, D; Cella, M; Franchi, A M

    2003-01-01

    Nitric oxide (NO) fulfils important functions during pregnancy and has a role in implantation, decidualization, vasodilatation and myometrial relaxation. However, at high concentrations, such as those that are produced in sepsis, NO has toxic effects as it is a free radical. The aim of this study was to characterize uterine and decidual NO production in lipopolysaccharide (LPS)-induced embryonic resorption in mice and to determine which isoforms of nitric oxide synthase (NOS) take part. LPS produced 100% embryonic resorption at 24 h, with complete fetus expulsions at 48 h. Decidual and uterine NO production were increased by LPS, with maximum production at 6 h. This increase was due to the induction of expression of inducible nitric oxide synthase (iNOS) isoform in the decidua and uterus, and neuronal nitric oxide synthase (nNOS) isoform in the decidua, as detected by western blot analysis and immunohistochemistry. LPS increased iNOS expression in decidual and myometrial cells and increased nNOS expression in decidual cells. In addition, LPS caused fibrinolysis and infiltration of mesometrial decidua by macrophages positive for iNOS and CD14 (LPS receptor). Endothelial nitric oxide synthase (eNOS) was found in decidual and uterine arteries but LPS did not modify its expression. LPS induced CD14 expression in endometrial glands, and this could have amplified the inflammatory response. Aminoguanidine, an inhibitor of iNOS activity, totally reversed the LPS-induced embryonic resorption. This result could be explained by an inhibition of the increase in NO production but also by an inhibition of the cellular infiltration and fibrinolysis. These results show that NO fulfils a fundamental role in LPS-induced embryonic resorption. PMID:12622700

  7. The fundamental role of increased production of nitric oxide in lipopolysaccharide-induced embryonic resorption in mice.

    PubMed

    Ogando, D G; Paz, D; Cella, M; Franchi, A M

    2003-01-01

    Nitric oxide (NO) fulfils important functions during pregnancy and has a role in implantation, decidualization, vasodilatation and myometrial relaxation. However, at high concentrations, such as those that are produced in sepsis, NO has toxic effects as it is a free radical. The aim of this study was to characterize uterine and decidual NO production in lipopolysaccharide (LPS)-induced embryonic resorption in mice and to determine which isoforms of nitric oxide synthase (NOS) take part. LPS produced 100% embryonic resorption at 24 h, with complete fetus expulsions at 48 h. Decidual and uterine NO production were increased by LPS, with maximum production at 6 h. This increase was due to the induction of expression of inducible nitric oxide synthase (iNOS) isoform in the decidua and uterus, and neuronal nitric oxide synthase (nNOS) isoform in the decidua, as detected by western blot analysis and immunohistochemistry. LPS increased iNOS expression in decidual and myometrial cells and increased nNOS expression in decidual cells. In addition, LPS caused fibrinolysis and infiltration of mesometrial decidua by macrophages positive for iNOS and CD14 (LPS receptor). Endothelial nitric oxide synthase (eNOS) was found in decidual and uterine arteries but LPS did not modify its expression. LPS induced CD14 expression in endometrial glands, and this could have amplified the inflammatory response. Aminoguanidine, an inhibitor of iNOS activity, totally reversed the LPS-induced embryonic resorption. This result could be explained by an inhibition of the increase in NO production but also by an inhibition of the cellular infiltration and fibrinolysis. These results show that NO fulfils a fundamental role in LPS-induced embryonic resorption.

  8. Ectopic bone regeneration by human bone marrow mononucleated cells, undifferentiated and osteogenically differentiated bone marrow mesenchymal stem cells in beta-tricalcium phosphate scaffolds.

    PubMed

    Ye, Xinhai; Yin, Xiaofan; Yang, Dawei; Tan, Jian; Liu, Guangpeng

    2012-07-01

    Tissue engineering approaches using the combination of porous ceramics and bone marrow mesenchymal stem cells (BMSCs) represent a promising bone substitute for repairing large bone defects. Nevertheless, optimal conditions for constructing tissue-engineered bone have yet to be determined. It remains unclear if transplantation of predifferentiated BMSCs is superior to undifferentiated BMSCs or freshly isolated bone marrow mononucleated cells (BMNCs) in terms of new bone formation in vivo. The aim of this study was to investigate the effect of in vitro osteogenic differentiation (β-glycerophosphate, dexamethasone, and l-ascorbic acid) of human BMSCs on the capability to form tissue-engineered bone in unloaded conditions after subcutaneous implantation in nude mice. After isolation from human bone marrow aspirates, BMNCs were divided into three parts: one part was seeded onto porous beta-tricalcium phosphate ceramics immediately and transplanted in a heterotopic nude mice model; two parts were expanded in vitro to passage 2 before cell seeding and in vivo transplantation, either under osteogenic conditions or not. Animals were sacrificed for micro-CT and histological evaluation at 4, 8, 12, 16, and 20 weeks postimplantation. The results showed that BMSCs differentiated into osteo-progenitor cells after induction, as evidenced by the altered cell morphology and elevated alkaline phosphatase activity and calcium deposition, but their clonogenicity, proliferating rate, and seeding efficacy were not significantly affected by osteogenic differentiation, compared with undifferentiated cells. Extensive new bone formed in the pores of all the scaffolds seeded with predifferentiated BMSCs at 4 weeks after implantation, and maintained for 20 weeks. On the contrary, scaffolds containing undifferentiated BMSCs revealed limited bone formation only in 1 out of 6 cases at 8 weeks, and maintained for 4 weeks. For scaffolds with BMNCs, woven bone was observed sporadically only in one

  9. M1-like Macrophage Polarization Promotes Orthodontic Tooth Movement.

    PubMed

    He, D; Kou, X; Yang, R; Liu, D; Wang, X; Luo, Q; Song, Y; Liu, F; Yan, Y; Gan, Y; Zhou, Y

    2015-09-01

    Macrophages play a crucial role in inflammatory-mediated bone loss. Orthodontic tooth movement (OTM) is associated with inflammatory bone remodeling. However, whether and how macrophages contribute to mechanical force-induced OTM remains unknown. In this study, we hypothesized that polarization of M1-like macrophages may contribute to the OTM. Orthodontic nickel-titanium springs were applied to the upper first molars of rats or mice to induce OTM. The distance of OTM gradually increased after mechanical force was applied to the rats for 5 and 10 d. M1-like macrophage polarization and expression of M1 cytokine tumor necrosis factor (TNF)-α also increased after force application. More importantly, monocyte/macrophage depletion in mice by injection of clodronate liposomes decreased the distance of OTM and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68(+) macrophages, accompanied by reduced expressions of M1 markers TNF-α and inducible nitric oxide synthase (iNOS), whereas systemic transfusion of M1 macrophages in mice increased them. Further experiments showed that injection of recombinant TNF-α increased the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as upregulated the expression of TNF-α and iNOS. Blockage of TNF-α by etanercept injection reduced the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as decreased the levels of TNF-α and iNOS. These data suggest that M1-like macrophage polarization promotes alveolar bone resorption and consequent OTM after mechanical force application.

  10. Osteoclast-independent bone resorption by fibroblast-like cells

    PubMed Central

    Pap, Thomas; Claus, Anja; Ohtsu, Susumu; Hummel, Klaus M; Schwartz, Peter; Drynda, Susanne; Pap, Géza; Machner, Andreas; Stein, Bernhard; George, Michael; Gay, Renate E; Neumann, Wolfram; Gay, Steffen; Aicher, Wilhelm K

    2003-01-01

    To date, mesenchymal cells have only been associated with bone resorption indirectly, and it has been hypothesized that the degradation of bone is associated exclusively with specific functions of osteoclasts. Here we show, in aseptic prosthesis loosening, that aggressive fibroblasts at the bone surface actively contribute to bone resorption and that this is independent of osteoclasts. In two separate models (a severe combined immunodeficient mouse coimplantation model and a dentin pit formation assay), these cells produce signs of bone resorption that are similar to those in early osteoclastic resorption. In an animal model of aseptic prosthesis loosening (i.e. intracranially self-stimulated rats), it is shown that these fibroblasts acquire their ability to degrade bone early on in their differentiation. Upon stimulation, such fibroblasts readily release acidic components that lower the pH of their pericellular milieu. Through the use of specific inhibitors, pericellular acidification is shown to involve the action of vacuolar type ATPases. Although fibroblasts, as mesenchymal derived cells, are thought to be incapable of resorbing bone, the present study provides the first evidence to challenge this widely held belief. It is demonstrated that fibroblast-like cells, under pathological conditions, may not only enhance but also actively contribute to bone resorption. These cells should therefore be considered novel therapeutic targets in the treatment of bone destructive disorders. PMID:12723988

  11. Bone remodeling and hydroxyapatite resorption in coated primary hip prostheses.

    PubMed

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

    2009-02-01

    Hydroxyapatite coatings for THA promote bone ongrowth, but bone and coating are exposed to stress shielding-driven osteoclastic resorption. We asked: (1) if the resorption of hydroxyapatite coating and bone ongrowth correlated with demographics; (2) if the resorption related to the stem level; and (3) what happens to the implant-bone interface when all hydroxyapatite coating is resorbed? We recovered 13 femoral components from cadaveric specimens 3.3 to 11.2 years after uneventful primary THA. Three cross sections (proximal, medial, distal) of the hydroxyapatite-coated proximal implant sleeve were analyzed by measuring the percentage of residual hydroxyapatite and bone ongrowth on the implant perimeter. Hydroxyapatite resorption was independent of patient age but increased with time in vivo and mostly was gone after 8 years. Bone ongrowth was independent of time in vivo but decreased with aging patients. Only in the most proximal section did less residual hydroxyapatite correlate with less bone ongrowth. Hydroxyapatite resorption, which was more proximal than distal, showed no adverse effects on the implant-bone interface.

  12. Stimulative effects of lead on bone resorption in organ culture.

    PubMed

    Miyahara, T; Komiyama, H; Miyanishi, A; Takata, M; Nagai, M; Kozuka, H; Hayashi, T; Yamamoto, M; Ito, Y; Odake, H

    1995-03-31

    To clarify whether hypercalcemia after injection of Pb to rats is due to biological bone resorption or physicochemical mineral dissolution, the effect of lead (Pb) on release of previously incorporated 45Ca in organ culture was investigated. Pb at 50 microM and above stimulated the release of 45Ca and hydroxyproline (Hyp). Pb did not stimulate 45Ca release from the bones inactivated by freezing and thawing. Eel calcitonin (ECT), bafilomycin A1 and scopadulcic acid B (SDB) inhibited Pb-stimulated 45Ca release. These results indicate that Pb-induced 45Ca release is due to osteoclastic bone resorption. Pb-stimulated bone resorption was inhibited by indomethacin and flurbiprofen. Pb stimulated the release of prostaglandin E2 (PGE2) from the bones into the media. There was significantly high correlation between 45Ca and PGE2 release. Pb-induced bone resorption was inferred to be mediated by PGE2. From these results, it was suggested that hypercalcemia after Pb injection might be caused by biological bone resorption.

  13. The effect of budesonide on orthodontic induced root resorption

    PubMed Central

    Aghili, Hosseinagha; Meybodi, Seyed Amir Reza Fatahi; Ardekani, Mohammed Danesh; Bemanianashkezari, Mohammad Hassan; Modaresi, Jalil; Masomi, Yousef; Moghadam, Mahdjoube Goldani

    2015-01-01

    Background: The aim of this study was to evaluate the hypothesis that budesonide increases the susceptibility of teeth to root resorption during the course of orthodontic treatment. Materials and Methods: A randomized controlled trial design (animal study) was employed. Budesonide was administered in test group for 14 days during which orthodontic force was applied to upper right molar. Afterwards, root resorption was measured on mesio-cervical and disto-apical parts of the mesial root on transverse histological sections. ANOVA and Bonfferoni tests were used. Statistical significance was considered to be P ≤ 0.05. Results: In general, the subgroups in which the force was applied showed significantly greater root resorption. Where force was applied there was no significant difference, whether budesonide was administered or not. While where there was no force, a group who received budesonide showed significantly greater root resorption than the other, unless at the coronal level where the difference was not significant. Conclusion: Within the limitations of this study, it seems budesonide could increase root resorption, but in the presence of orthodontic force this effect is negligible. PMID:26288626

  14. Spontaneous resorption of a large cervical herniated nucleus pulposus.

    PubMed

    Cvetanovich, Gregory L; Hsu, Andrew R; Frank, Rachel M; An, Howard S; Andersson, Gunnar B

    2014-07-01

    The majority of patients with symptomatic herniated discs can be successfully and conservatively managed and can achieve clinical improvement without surgical intervention. Resorption of the herniated nucleus pulposus (HNP) is 1 conservative mechanism for clinical improvement. We present the case of a 76-year-old healthy man with acute cervical radicular right arm pain and positive Spurling test. Magnetic resonance imaging (MRI) showed a large disc extrusion behind the C6 vertebral body, causing severe central canal stenosis and right-greater-than-left foraminal stenosis. The patient did not want surgical intervention, and his symptoms resolved with conservative treatment. A follow-up MRI 7 months after his initial presentation showed almost complete resorption of the herniated disc. The patient returned to his normal activities and has not had recurrence of symptoms for 2 years. This report provides an interesting example of complete resorption of a large, extruded cervical herniated disc in a symptomatic patient and a review of the literature on resorption of herniated discs. The review suggests that larger herniations with an epidural location (penetration of the posterior longitudinal ligament) have a greater chance of resorption.

  15. Commercial Honeybush (Cyclopia spp.) Tea Extract Inhibits Osteoclast Formation and Bone Resorption in RAW264.7 Murine Macrophages—An in vitro Study

    PubMed Central

    Visagie, Amcois; Kasonga, Abe; Deepak, Vishwa; Moosa, Shaakirah; Marais, Sumari; Kruger, Marlena C.; Coetzee, Magdalena

    2015-01-01

    Honeybush tea, a sweet tasting caffeine-free tea that is indigenous to South Africa, is rich in bioactive compounds that may have beneficial health effects. Bone remodeling is a physiological process that involves the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. When resorption exceeds formation, bone remodeling can be disrupted resulting in bone diseases such as osteoporosis. Osteoclasts are multinucleated cells derived from hematopoietic precursors of monocytic lineage. These precursors fuse and differentiate into mature osteoclasts in the presence of receptor activator of NF-kB ligand (RANKL), produced by osteoblasts. In this study, the in vitro effects of an aqueous extract of fermented honeybush tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macrophages. We found that commercial honeybush tea extract inhibited osteoclast formation and TRAP activity which was accompanied by reduced bone resorption and disruption of characteristic cytoskeletal elements of mature osteoclasts without cytotoxicity. Furthermore, honeybush tea extract decreased expression of key osteoclast specific genes, matrix metalloproteinase-9 (MMP-9), tartrate resistant acid phosphatase (TRAP) and cathepsin K. This study demonstrates for the first time that honeybush tea may have potential anti-osteoclastogenic effects and therefore should be further explored for its beneficial effects on bone. PMID:26516894

  16. Management of Root Resorption Using Chemical Agents: A Review

    PubMed Central

    Mohammadi, Zahed; C. Cehreli, Zafer; Shalavi, Sousan; Giardino, Luciano; Palazzi, Flavio; Asgary, Saeed

    2016-01-01

    Root resorption (RR) is defined as the loss of dental hard tissues because of clastic activity inside or outside of tooth the root. In the permanent dentition, RR is a pathologic event; if untreated, it might result in the premature loss of the affected tooth. Several hypotheses have been suggested as the mechanisms of root resorption such as absence of the remnants of Hertwig's epithelial root sheath (HERS) and the absence of some intrinsic factors in cementum and predentin such as amelogenin or osteoprotegerin (OPG). It seems that a barrier is formed by the less-calcified intermediate cementum or the cementodentin junction that prevents external RR. There are several chemical strategies to manage root resorption. The purpose of this paper was to review several chemical agents to manage RR such as tetracycline, sodium hypochlorite, acids (citric acid, phosphoric acid, ascorbic acid and hydrochloric acid), acetazolamide, calcitonin, alendronate, fluoride, Ledermix and Emdogain. PMID:26843869

  17. Factors connected with alveolar bone resorption among institutionalized elderly people.

    PubMed

    de Baat, C; Kalk, W; van 't Hof, M

    1993-10-01

    In this socio-dental investigation among 175 institutionalized somatically disabled edentulous elderly people correlations are described between the test subjects' degree of alveolar bone resorption, their gender and age, their duration of edentulousness, and the number of complete dentures worn. All test subjects were interviewed by dental students and clinically examined by dentists. The mandibular alveolar bone resorption was significantly stronger in women than in men and stronger in people who had been edentulous longer. The longer the test subjects had been edentulous and the greater their degree of mandibular alveolar bone resorption was, the more mandibular dentures they had worn. This study among institutionalized elderly people provides for the most part the same results as a previously presented study among much younger people. Obviously, in these respects there are no differences between these groups.

  18. Apical External Root Resorption and Repair in Orthodontic Tooth Movement: Biological Events

    PubMed Central

    Thomadakis, George; Fourie, Jeanine; Lemmer, Johan

    2016-01-01

    Some degree of external root resorption is a frequent, unpredictable, and unavoidable consequence of orthodontic tooth movement mediated by odontoclasts/cementoclasts originating from circulating precursor cells in the periodontal ligament. Its pathogenesis involves mechanical forces initiating complex interactions between signalling pathways activated by various biological agents. Resorption of cementum is regulated by mechanisms similar to those controlling osteoclastogenesis and bone resorption. Following root resorption there is repair by cellular cementum, but factors mediating the transition from resorption to repair are not clear. In this paper we review some of the biological events associated with orthodontically induced external root resorption. PMID:27119080

  19. Hydroxyapatite and urate crystal induced cytokine release by macrophages.

    PubMed Central

    Alwan, W H; Dieppe, P A; Elson, C J; Bradfield, J W

    1989-01-01

    Destructive osteoarthritis is characterised by rapidly progressive joint destruction associated with intra-articular deposition of hydroxyapatite crystals. The possible role of such crystals in the pathogenesis of this condition was investigated by testing the ability of hydroxyapatite crystals to stimulate the production of bone resorbing activity from mouse peritoneal macrophages. Urate crystals were used for comparison. Culture supernatants were tested for bone resorbing activity using the mouse calvarial bone resorption assay, for interleukin 1 using a standard lymphocyte activation assay, and for prostaglandin E2 by radioimmunoassay. Culture supernatants from macrophages incubated with hydroxyapatite crystals contained dialysable bone resorbing activity, high concentrations of prostaglandin E2, but no interleukin 1 like activity. The production of the bone resorbing agent was prevented by culturing macrophages with hydroxyapatite crystals in the presence of indomethacin. By contrast, culture supernatants from macrophages incubated with urate crystals contained bone resorbing activity, which was only partly removed by dialysis, and interleukin 1 like activity. The latter was shown to be increased in culture supernatants from macrophages incubated with urate crystals in the presence of indomethacin, while production of bone resorbing activity was partially inhibited. It is considered that the bone resorbing activity liberated from macrophages stimulated by hydroxyapatite crystals can be explained by the presence of prostaglandin E2 alone, whereas the activity liberated by urate crystals is due to both prostaglandin E2 and interleukin 1. PMID:2545171

  20. The effect of photobiomodulation on root resorption during orthodontic treatment

    PubMed Central

    Nimeri, Ghada; Kau, Chung H; Corona, Rachel; Shelly, Jeffery

    2014-01-01

    Photobiomodulation is used to accelerate tooth movement during orthodontic treatments. The changes in root morphology in a group of orthodontic patients who received photobiomodulation were evaluated using the cone beam computed tomography technique. The device used is called OrthoPulse, which produces low levels of light with a near infrared wavelength of 850 nm and an intensity of 60 mW/cm2 continuous wave. Twenty orthodontic patients were recruited for these experiments, all with class 1 malocclusion and with Little’s Irregularity Index (>2 mm) in either of the arches. Root resorption was detected by measuring changes in tooth length using cone beam computed tomography. These changes were measured before the orthodontic treatment and use of low-level laser therapy and after finishing the alignment level. Little’s Irregularity Index for all the patients was calculated in both the maxilla and mandible and patients were divided into three groups for further analysis, which were then compared to the root resorption measurements. Our results showed that photobiomodulation did not cause root resorption greater than the normal range that is commonly detected in orthodontic treatments. Furthermore, no correlation between Little’s Irregularity Index and root resorption was detected. PMID:24470774

  1. Management of Internal Root Resorption on Permanent Teeth

    PubMed Central

    Bonte, Eric; Bayet, François; Lasfargues, Jean-Jacques

    2013-01-01

    Internal root resorption (IRR) is a particular category of pulp disease characterized by the loss of dentine as a result of the action of clastic cells stimulated by pulpal inflammation. This review article explains the etiology, the prevalence of IRR, and, in addition to the clinical data, the contribution of the three-dimensional imaging (CBCT) to the diagnosis, the clinical decision, and the therapeutic management of IRR. The authors discussed the various therapeutic options including the orthograde or retrograde fillings of the root canal resorption area. Root canal treatment remains the treatment of choice of internal root resorption as it removes the granulation tissue and blood supply of the clastic cells. The authors describe with different clinical cases the modern endodontic techniques including optical aids, ultrasonic improvement of chemical debridement, and the use of alternative materials such as calcium silicate combined with thermoplastic filling (warm gutta-percha). In these conditions, the prognosis of the conservative treatment of internal resorptions, even if root walls are perforated, is good. PMID:24348560

  2. Varicella Zoster Virus and Internal Root Resorption: A Case Report.

    PubMed

    Talebzadeh, Bita; Rahimi, Saeed; Abdollahi, Amir Ardalan; Nouroloyuni, Ahmad; Asghari, Vahide

    2015-08-01

    Herpes zoster is a viral infection caused by the reactivation of the varicella zoster virus. One of the less well-recognized maxillofacial complications is tooth root resorption. To our knowledge, this is the first case report about internal resorption associated with varicella zoster virus involving different dental quadrants. A 38-year-old woman presented with internal resorption of maxillary canine and first premolar tooth roots on the right quadrant and generalized internal resorption of second molars of both mandibular quadrants. The patient's medical history showed mild oral lichen planus and infection with varicella zoster virus (chickenpox) with severe clinical manifestations 5 years previously. The patient developed diabetes mellitus type I and hypothyroidism a short time after varicella zoster virus infection, and by the time of infection with this virus, oral lichen planus had progressed from the reticular pattern to the generalized severe erosive form. Viral etiology could also be considered in these diseases. The root canals of the affected teeth were debrided, irrigated, and dried, and calcium hydroxide paste was placed in the root canals for a week during the first treatment session. The root canals were obturated during the second session. Six-month follow-up showed improvement of oral lichen planus and resolution of widening of periodontal ligament of the affected teeth, with follow-up radiographs revealing no periapical problems. It appears some cases of internal root resorption classified as idiopathic might have viral etiology. Therefore, it is recommended that patients be questioned about a history of chickenpox and herpes zoster.

  3. Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity.

    PubMed

    Irie, Atsushi; Takami, Masamichi; Kubo, Hideo; Sekino-Suzuki, Naoko; Kasahara, Kohji; Sanai, Yutaka

    2007-08-01

    Heparin is a highly sulfated glycosaminoglycan and has been shown to activate osteoclastic bone resorption though how is not yet clear. Here we investigate the molecule involved in heparin-induced activation of osteoclasts using an in vitro osteoclast culture assay. The formation and activation of osteoclasts are induced by receptor activator of NFkappaB ligand (RANKL) on osteoblasts, and inhibited by osteoprotegerin (OPG), a decoy receptor of RANKL, which is secreted from osteoblasts. In a coculture of mouse bone marrow cells and osteoblasts treated with 1,25-dihydroxyvitamin D(3) and prostaglandin E(2) on dentin slices, the bone marrow cells differentiate into osteoclasts, and resorption pits are formed on the dentin slices. Addition of heparin, various glycosaminoglycans, and chemically modified heparins to the coculture reveals that heparin enhances the pit-forming activity of osteoclasts, and this effect of heparin on the activation of osteoclasts is dependent on its sugar chain structure. By contrast, mRNA expression levels of RANKL, RANK, and OPG in the coculture are not altered by heparin treatment. Furthermore, neither RANK nor RANKL binds to heparin, suggesting that heparin does not directly interact with these proteins. Instead, heparin specifically binds to OPG and prevents OPG-mediated inhibition of osteoclastic bone resorption in the coculture. Heparin treatment does not enhance osteoclastic bone resorption in a monoculture of osteoclasts derived from bone marrow cells, and in the coculture using osteoblasts from OPG-deficient mice. A (125)I-OPG binding assay showed that OPG binds to osteoblasts and that this binding is inhibited by the addition of heparin, suggesting that OPG binds to RANKL on the osteoblast membrane and that heparin blocks this interaction. These results demonstrate that heparin enhances osteoclastic bone resorption by inhibiting OPG activity.

  4. Management of A Rare Case of Communicating Internal-External Inflammatory Resorption

    PubMed Central

    Arora, Suraj; Saluja, Priyanka; Setia, Vikas

    2015-01-01

    The present case describes the successful management of a rare case of communicating internal-external resorption in which both internal and external resorption seem to develop independent of each other. The case report highlights the importance of correct diagnosis and need of revision of classification system of resorptive defects. PMID:26155588

  5. Serum amyloid A inhibits osteoclast differentiation to maintain macrophage function.

    PubMed

    Kim, Jiseon; Yang, Jihyun; Park, Ok-Jin; Kang, Seok-Seong; Yun, Cheol-Heui; Han, Seung Hyun

    2016-04-01

    Serum amyloid A is an acute phase protein that is elevated under inflammatory conditions. Additionally, the serum levels of serum amyloid A are associated with the progression of inflammatory arthritis; thus, serum amyloid A might be involved in the regulation of osteoclast differentiation. In the present study, we examined the effects of serum amyloid A on osteoclast differentiation and function. When bone marrow-derived macrophages, as osteoclast precursors, were stimulated with serum amyloid A in the presence of M-CSF and receptor activator of nuclear factor-κB ligand, osteoclast differentiation and its bone-resorption activity were substantially inhibited. TLR2 was important in the inhibitory effect of serum amyloid A on osteoclast differentiation, because serum amyloid A stimulated TLR2. The inhibitory effect was absent in bone marrow-derived macrophages obtained from TLR2-deficient mice. Furthermore, serum amyloid A inhibited the expression of c-Fos and nuclear factor of activated T cells c1, which are crucial transcription factors for osteoclast differentiation, but prevented downregulation of IFN regulatory factor-8, a negative regulator of osteoclast differentiation. In contrast, serum amyloid A sustained the endocytic capacity of bone marrow-derived macrophages and their ability to induce the proinflammatory cytokines, IL-6, IL-1β, and TNF-α. Taken together, these results suggest that serum amyloid A, when increased by inflammatory conditions, inhibits differentiation of macrophages to osteoclasts, likely to maintain macrophage function for host defense.

  6. Experimental study of diamond resorption during mantle metasomatism

    NASA Astrophysics Data System (ADS)

    Fedorchuk, Yana; Schmidt, Max W.; Liebske, Christian

    2014-05-01

    Many of kimberlite-derived diamonds are partially dissolved to various degree but show similar resorption style. This resorption style has been observed in experiments with aqueous fluid at the conditions corresponding to kimberlite emplacement (1-2 GPa). At the same time, each diamond population has more than ten percent of diamond crystals with several drastically different resorption styles, which have not been observed in experiments, and may represent partial dissolution of diamonds during metasomatism in different mantle domains. Metasomatic processes modify the composition of subcratonic mantle, may trigger the formation of kimberlite magma, and result in the growth and partial dissolution of diamonds. Composition of metasomatic agents as constrained from studies of the reaction rims on mantle minerals (garnet, clinopyroxene) and experimental studies vary between carbonatitic melt, aqueous silicate melt, and CHO fluid. However, complex chemical pattern of mantle minerals and estimates of redox regime in subcratonic mantle allow different interpretations. Here we explore diamond dissolution morphology as an indicator of the composition of mantle metasomatic agents. Towards this end we examine diamond dissolution morphologies developed in experiments at the conditions of mantle metasomatism in different reacting media and compare them to the mantle-derived dissolution features of natural diamonds. The experiments were conducted in multi-anvil (Walker-Type) apparatus at 6 GPa and 1200-1500oC. Dissolution morphology of natural octahedral diamond crystals (0.5 mg) was examined in various compositions in synthetic system MgO-CaO- SiO2-CO2-H2O. The runs had the following phases present: solid crystals with fluid (various ratio of H2O-CO2-SiO2, and in the air), carbonate melt, carbonate-silicate melt, and carbonate melt with CHO fluid. Experiments produced three different styles of diamond resorption. In the presence of a fluid phase with variable proportions of H2O

  7. Idiopathic Radiographic Apical Root Resorption in Wind Instrument Players.

    PubMed

    Shafi, Imran; Welbury, Richard

    2015-12-01

    Root resorption of the permanent teeth involves an elaborate interaction among inflammatory cells resulting in loss of dental hard tissues. This report describes three clinical cases where idiopathic root resorption occurred in wind instrument playing patients. These patients produce adequate non-orthodontic forces, while playing their instruments, to expose their teeth to root resorbing force. Careful clinical monitoring of patients' teeth should be undertaken, as the additive effects of orthodontic treatment and musical habits are unknown. CPD/Clinical Relevance: This paper advises that questioning about wind instrument playing during case history-taking would be beneficial to clinicians. Furthermore, careful clinical monitoring of these patients' teeth during orthodontic treatment should be undertaken. PMID:26856005

  8. Collagen cross-linking and resorption: effect of glutaraldehyde concentration.

    PubMed

    Roe, S C; Milthorpe, B K; Schindhelm, K

    1990-12-01

    Cross-linked collagen bioprostheses usually are designed to be inert and nonresorbable, resulting in fatigue and wear failure in high-stress environments. Eventual replacement of the implant, although minimizing strength loss during resorption, would result in a graft with reparative ability. Kangaroo tail tendon (KTT) partially cross-linked with glutaraldehyde (GA) was evaluated in vitro for resistance to bacterial collagenase digestion and in vivo for biocompatibility and resorbability in an intramuscular implant assay. Cross-linking was quantified by thermal denaturation studies. Incomplete cross-linking was achieved with concentrations of GA less than 0.1% (w/v). KTT cross-linked in greater than or equal to 0.05% GA were collagenase resistant being incompletely digested after 240 h. Cross-linking of KTT with low concentrations of GA resulted in partial collagenase resistance and slowed resorption. PMID:2126427

  9. Multiple idiopathic external and internal resorption: Case report with cone-beam computed tomography findings

    PubMed Central

    Uzuntas, Ceren Feriha; Kurt, Hakan

    2014-01-01

    Root resorption is loss of dental hard tissue as a result of clastic activities. The dental hard tissue of permanent teeth does not normally undergo resorption, except in cases of inflammation or trauma. However, there are rare cases of tooth resorption of an unknown cause, known as "idiopathic root resorption." This report would discuss a rare case of multiple idiopathic resorption in the permanent maxillary and mandibular teeth of an otherwise healthy 36-year-old male patient. In addition to a clinical examination, the patient was imaged using conventional radiography and cone-beam computed tomography (CBCT). The examinations revealed multiple external and internal resorption of the teeth in all four quadrants of the jaws with an unknown cause. Multiple root resorption is a rare clinical phenomenon that should be examined using different radiographic modalities. Cross-sectional CBCT is useful in the diagnosis and examination of such lesions. PMID:25473640

  10. Different cysteine proteinases involved in bone resorption and osteoclast formation.

    PubMed

    Brage, M; Abrahamson, M; Lindström, V; Grubb, A; Lerner, U H

    2005-06-01

    Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.

  11. Variation in the sizes of resorption lacunae made in vitro.

    PubMed

    Jones, S J; Boyde, A; Ali, N N; Maconnachie, E

    1986-01-01

    The assessment of in vitro osteoclastic activity has, until recently, been dependent on the analysis of organ culture experiments. We have developed a single cell resorption assay so that the resorptive function of individual osteoclasts could be studied. This paper examines the biological variation in the sizes of resorption lacunae produced by bone cell cultures derived from neonate rats and rabbits, and prehatch or hatchling chicks. Cultures were run for 24h for all species; and in addition for 48h for rat, 9 or 12 hours for rabbit and 3-7 hours for chick. The numbers of the nuclei of osteoclasts seeded on to plastic were counted for all three species. SEM stereophotogrammetry was used to measure areas, volumes, and maximum and average depths of the lacunae using specially designed instruments and software. Rat osteoclasts were smallest, and more chick osteoclasts were very large. There was a species difference in the onset of resorption and the sizes of pits produced, the chick osteoclasts being more vigorous resorbers than the rabbit ones, and the rat least so. For a given plan area, chick lacunae were deeper. There was a high correlation between area and volume. The range of maximum depths for a given area was high, however. Thus the mean of a few measurements of depths should not be used to calculate volume from area. At 24 hours, 77% of the rat, 47% of the rabbit and 28% of the chick lacunae were less than 1,000 microns 3 in volume; and 11% of the rat, 17% of the rabbit and 22% of the chick lacunae were between 1,000 and 2,000 microns 3 in volume. The mean values at 24 hours were 981, 2796, and 4582 microns 3 for rat, rabbit and chick lacunae respectively.

  12. Resorptive tooth root lesions in the Malayan tapir (Tapirus indicus).

    PubMed

    Da Silva, Mari-Ann O; Kortegaard, Hanne E; Choong, Siew Shean; Arnbjerg, Jens; Bertelsen, Mads F

    2011-03-01

    Facial abscessation and osteomyelitis due to dental disease is commonly seen in the Malayan tapir (Tapirus indicus), but little is known about the prevalence or etiology of these lesions. To determine the prevalence of dental ailments, 56 skulls and mandibles of deceased Malayan tapirs were visually and radiographically evaluated. Dental lesions were scored according to severity, and individuals were classified according to their age (juvenile/ young adult/adult) and origin (captive/free ranging). All of the lesions identified were of a resorptive nature. seemingly originating at the cementoenamel junction and burrowing towards the center of the tooth. Overall, 27% of the investigated skulls presented radiolucent dental lesions. The prevalence among captive animals was 52% (13/25), while only 6% (2/31) of the free-ranging tapirs had dental lesions. The second, third, and fourth premolars and first molar were the teeth most commonly affected, and the mandibular teeth were more often involved than the maxillary dentition. This study demonstrates a high prevalence of resorptive dental lesions in captive Malayan tapirs and provides a strong indication that age and captivity are significant risk factors in the development of these lesions. Dental disease, Malayan tapir, radiology, resorptive lesions, Tapirus indicus. PMID:22946368

  13. Conservative Management of Invasive Cervical Resorption: A Case Report

    PubMed Central

    Umer, Fahad; Adnan, Samira; Raza Khan, Farhan

    2013-01-01

    Invasive cervical resorption is a condition that affects the root surface area below the epithelial attachment. Multiple treatment modalities are advocated, involving exposure of the invasive defect, removal of the granulation tissue and sealing with various restorative materials. This report demonstrates conservative treatment of a patient presenting with peri-apical periodontitis in upper right central and lateral incisors, along with Class II invasive resorption defect cervically on the mesial aspect of the central incisor, as a result of trauma. As the patient was not willing for any surgical intervention, only ortho-grade root canal treatment was carried out in both teeth, with Calcium hydroxide as intra-canal medicament. At three year follow-up, the patient remains asymptomatic demonstrating radiographic evidence of infilling of defect with bone-like tissue. Within the limitations of this report, it was seen that this conservative method for halting the progression of invasive cervical resorption could be under taken in patients who are un-willing for surgical intervention or in whom surgery is contra-indicated. PMID:25512757

  14. Resorptive tooth root lesions in the Malayan tapir (Tapirus indicus).

    PubMed

    Da Silva, Mari-Ann O; Kortegaard, Hanne E; Choong, Siew Shean; Arnbjerg, Jens; Bertelsen, Mads F

    2011-03-01

    Facial abscessation and osteomyelitis due to dental disease is commonly seen in the Malayan tapir (Tapirus indicus), but little is known about the prevalence or etiology of these lesions. To determine the prevalence of dental ailments, 56 skulls and mandibles of deceased Malayan tapirs were visually and radiographically evaluated. Dental lesions were scored according to severity, and individuals were classified according to their age (juvenile/ young adult/adult) and origin (captive/free ranging). All of the lesions identified were of a resorptive nature. seemingly originating at the cementoenamel junction and burrowing towards the center of the tooth. Overall, 27% of the investigated skulls presented radiolucent dental lesions. The prevalence among captive animals was 52% (13/25), while only 6% (2/31) of the free-ranging tapirs had dental lesions. The second, third, and fourth premolars and first molar were the teeth most commonly affected, and the mandibular teeth were more often involved than the maxillary dentition. This study demonstrates a high prevalence of resorptive dental lesions in captive Malayan tapirs and provides a strong indication that age and captivity are significant risk factors in the development of these lesions. Dental disease, Malayan tapir, radiology, resorptive lesions, Tapirus indicus.

  15. Fluid pressure and flow as a cause of bone resorption

    PubMed Central

    Fahlgren, Anna

    2010-01-01

    Background Unstable implants in bone become surrounded by an osteolytic zone. This is seen around loose screws, for example, but may also contribute to prosthetic loosening. Previous animal studies have shown that such zones can be induced by fluctuations in fluid pressure or flow, caused by implant instability. Method To understand the roles of pressure and flow, we describe the 3-dimensional distribution of osteolytic lesions in response to fluid pressure and flow in a previously reported rat model of aseptic loosening. 50 rats had a piston inserted in the proximal tibia, designed to produce 20 local spikes in fluid pressure of a clinically relevant magnitude (700 mmHg) twice a day. The spikes lasted for about 0.3 seconds. After 2 weeks, the pressure was measured in vivo, and the osteolytic lesions induced were studied using micro-CT scans. Results Most bone resorption occurred at pre-existing cavities within the bone in the periphery around the pressurized region, and not under the piston. This region is likely to have a higher fluid flow and less pressure than the area just beneath the piston. The velocity of fluid flow was estimated to be very high (roughly 20 mm/s). Interpretation The localization of the resorptive lesions suggests that high-velocity fluid flow is important for bone resorption induced by instability. PMID:20718695

  16. Uptake and loss of plutonium from osteoclasts and macrophages in the mandibular condyle of the rat.

    PubMed

    Priest, N D; Giannola, S J

    1980-01-01

    Female rats were used to study the kinetics of plutonium transfer from the bone surfaces of the mandibular condyle to osteoclasts and macrophages. This study was made using autoradiographs prepared from plastic sections of the mineralized bones of animals which had been injected with 241 Pu citrate. Measurements of the concentration of plutonium in the osteoclasts and macrophages at different times after the injection of plutonium showed that plutonium was concentrated by osteoclasts from bone surfaces and was retained with a half-time of approximately 70 h. Subsequently, plutonium appeared to be transferred to macrophages. The results showed that plutonium was unlikely to be accumulated by macrophages as a result of their participation in bone resorption.

  17. Influence of Bisphosphonate Treatment on Medullary Macrophages and Osteoclasts: An Experimental Study

    PubMed Central

    Escudero, Natalia Daniela; Mandalunis, Patricia Mónica

    2012-01-01

    Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU) on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc); number of BrdU-positive nuclei (N.Nu BrdU+/Oc); percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc); medullary macrophage number (mac/mm2) and correlation between N.Nu/Oc and mac/mm2. Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm2. Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors. PMID:23008775

  18. Triptolide Inhibits Osteoclast Differentiation and Bone Resorption In Vitro via Enhancing the Production of IL-10 and TGF-β1 by Regulatory T Cells

    PubMed Central

    Xu, Huihui; Zhao, Hongyan; Wang, Gui; Huang, Jing; Guo, Minghui; Guo, Baosheng; Tan, Yong

    2016-01-01

    Triptolide, a purified component of Tripterygiumwilfordii Hook F, has been shown to have immunosuppressive and anti-inflammatory properties in rheumatoid arthritis (RA). Although triptolide has demonstrated that it could suppress bone destruction in collagen-induced mice, its therapeutic mechanism remains unclear. Many studies have investigated the effect of triptolide on Tregs and Tregs-related cytokine involved in RA. Additionally, previous studies have implied that Tregs inhibit osteoclast differentiation and bone resorption. Thus, in this study we aimed to explore the regulatory mechanism by which triptolide influences the Treg-mediated production of IL-10 and TGF-β1 to affect osteoclast differentiation and bone resorption. In cocultures system of Tregs and mouse bone marrow macrophages (BMMs), Tregs inhibited the differentiation of osteoclasts and reduced the resorbed areas significantly and the production of both IL-10 and TGF-β1 was upregulated. When the coculture systems were pretreated with triptolide, they produced higher levels of IL-10 and TGF-β1. Our data indicate that triptolide enhances the suppressive effects of Tregs on osteoclast differentiation and bone resorption by enhancing the secretion of IL-10 and TGF-β1. Tregs are most likely involved in the triptolide-mediated regulation of bone metabolism and may provide a potential therapeutic target for the treatment of inflammatory bone destruction. PMID:27413257

  19. Salicortin inhibits osteoclast differentiation and bone resorption by down-regulating JNK and NF-κB/NFATc1 signaling pathways.

    PubMed

    Nie, Shaobo; Xu, Jiawei; Zhang, Chenghua; Xu, Chen; Liu, Ming; Yu, Degang

    2016-01-29

    Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases.

  20. Botryllus schlosseri (Tunicata) whole colony irradiation: Do senescent zooid resorption and immunological resorption involve similar recognition events

    SciTech Connect

    Rinkevich, B.; Weissman, I.L. )

    1990-02-01

    The colonial tunicate Botryllus schlosseri undergoes cyclic blastogenesis where feeding zooids are senescened and resorbed and a new generation of zooids takes over the colony. When non-identical colonies come into direct contact, they either reject each other or fuse. Fusion is usually followed by the resorption of one of the partners in the chimera (immunological resorption). The striking morphological similarities between the two resorption phenomena suggest that both may involve tissue destruction following self-nonself recognition events. Here we attempt to modify these two events by whole colony gamma irradiation assays. Three sets of experiments were performed: (1) different doses of whole colony irradiation for determination of irradiation effects (110 colonies); (2) pairs of irradiated-nonirradiated isografts of clonal replicates for the potential of reconstruction of the irradiated partners (23 pairs); (3) chimeras of irradiated-nonirradiated partners for analysis of resorption hierarchy. Mortality increased with the irradiation dose. All colonies exposed to more than 5,000 rads died within 19 days, while no colony died below 2,000 rads. The average mortality periods, in days, for doses of 6,000-8,000, 5,000, and 2,500-4,000 rads were 14.4 +/- 3.1 (n = 24), 19.8 +/- 6.0 (n = 15), and 19.6 + 5.1 (n = 22), respectively. Younger colonies (3-6 months old) may survive radiation better than older ones (more than 13 months). Many morphological alterations were recorded in irradiated colonies: ampullar contraction and/or dilation, accumulation of pigment cells within ampullae, abnormal bleeding from blood vessels, sluggish blood circulation, necrotic zones, reduction in bud number, and irregularities in zooid and system structures. With doses of 3,000-4,000 rads and above, irradiation arrested the formation of new buds and interrupted normal takeover.

  1. Responses of plant nutrient resorption to phosphorus addition in freshwater marsh of Northeast China

    PubMed Central

    Mao, Rong; Zeng, De-Hui; Zhang, Xin-Hou; Song, Chang-Chun

    2015-01-01

    Anthropogenic activities have increased phosphorus (P) inputs to most aquatic and terrestrial ecosystems. However, the relationship between plant nutrient resorption and P availability is still unclear, and much less is known about the underlying mechanisms. Here, we used a multi-level P addition experiment (0, 1.2, 4.8, and 9.6 g P m−2 year−1) to assess the effect of P enrichment on nutrient resorption at plant organ, species, and community levels in a freshwater marsh of Northeast China. The response of nutrient resorption to P addition generally did not vary with addition rates. Moreover, nutrient resorption exhibited similar responses to P addition across the three hierarchical levels. Specifically, P addition decreased nitrogen (N) resorption proficiency, P resorption efficiency and proficiency, but did not impact N resorption efficiency. In addition, P resorption efficiency and proficiency were linearly related to the ratio of inorganic P to organic P and organic P fraction in mature plant organs, respectively. Our findings suggest that the allocation pattern of plant P between inorganic and organic P fractions is an underlying mechanism controlling P resorption processes, and that P enrichment could strongly influence plant-mediated biogeochemical cycles through altered nutrient resorption in the freshwater wetlands of Northeast China. PMID:25631373

  2. Responses of plant nutrient resorption to phosphorus addition in freshwater marsh of Northeast China

    NASA Astrophysics Data System (ADS)

    Mao, Rong; Zeng, De-Hui; Zhang, Xin-Hou; Song, Chang-Chun

    2015-01-01

    Anthropogenic activities have increased phosphorus (P) inputs to most aquatic and terrestrial ecosystems. However, the relationship between plant nutrient resorption and P availability is still unclear, and much less is known about the underlying mechanisms. Here, we used a multi-level P addition experiment (0, 1.2, 4.8, and 9.6 g P m-2 year-1) to assess the effect of P enrichment on nutrient resorption at plant organ, species, and community levels in a freshwater marsh of Northeast China. The response of nutrient resorption to P addition generally did not vary with addition rates. Moreover, nutrient resorption exhibited similar responses to P addition across the three hierarchical levels. Specifically, P addition decreased nitrogen (N) resorption proficiency, P resorption efficiency and proficiency, but did not impact N resorption efficiency. In addition, P resorption efficiency and proficiency were linearly related to the ratio of inorganic P to organic P and organic P fraction in mature plant organs, respectively. Our findings suggest that the allocation pattern of plant P between inorganic and organic P fractions is an underlying mechanism controlling P resorption processes, and that P enrichment could strongly influence plant-mediated biogeochemical cycles through altered nutrient resorption in the freshwater wetlands of Northeast China.

  3. Responses of plant nutrient resorption to phosphorus addition in freshwater marsh of Northeast China.

    PubMed

    Mao, Rong; Zeng, De-Hui; Zhang, Xin-Hou; Song, Chang-Chun

    2015-01-29

    Anthropogenic activities have increased phosphorus (P) inputs to most aquatic and terrestrial ecosystems. However, the relationship between plant nutrient resorption and P availability is still unclear, and much less is known about the underlying mechanisms. Here, we used a multi-level P addition experiment (0, 1.2, 4.8, and 9.6 g P m(-2) year(-1)) to assess the effect of P enrichment on nutrient resorption at plant organ, species, and community levels in a freshwater marsh of Northeast China. The response of nutrient resorption to P addition generally did not vary with addition rates. Moreover, nutrient resorption exhibited similar responses to P addition across the three hierarchical levels. Specifically, P addition decreased nitrogen (N) resorption proficiency, P resorption efficiency and proficiency, but did not impact N resorption efficiency. In addition, P resorption efficiency and proficiency were linearly related to the ratio of inorganic P to organic P and organic P fraction in mature plant organs, respectively. Our findings suggest that the allocation pattern of plant P between inorganic and organic P fractions is an underlying mechanism controlling P resorption processes, and that P enrichment could strongly influence plant-mediated biogeochemical cycles through altered nutrient resorption in the freshwater wetlands of Northeast China.

  4. Responses of plant nutrient resorption to phosphorus addition in freshwater marsh of Northeast China.

    PubMed

    Mao, Rong; Zeng, De-Hui; Zhang, Xin-Hou; Song, Chang-Chun

    2015-01-01

    Anthropogenic activities have increased phosphorus (P) inputs to most aquatic and terrestrial ecosystems. However, the relationship between plant nutrient resorption and P availability is still unclear, and much less is known about the underlying mechanisms. Here, we used a multi-level P addition experiment (0, 1.2, 4.8, and 9.6 g P m(-2) year(-1)) to assess the effect of P enrichment on nutrient resorption at plant organ, species, and community levels in a freshwater marsh of Northeast China. The response of nutrient resorption to P addition generally did not vary with addition rates. Moreover, nutrient resorption exhibited similar responses to P addition across the three hierarchical levels. Specifically, P addition decreased nitrogen (N) resorption proficiency, P resorption efficiency and proficiency, but did not impact N resorption efficiency. In addition, P resorption efficiency and proficiency were linearly related to the ratio of inorganic P to organic P and organic P fraction in mature plant organs, respectively. Our findings suggest that the allocation pattern of plant P between inorganic and organic P fractions is an underlying mechanism controlling P resorption processes, and that P enrichment could strongly influence plant-mediated biogeochemical cycles through altered nutrient resorption in the freshwater wetlands of Northeast China. PMID:25631373

  5. A SCANNING ELECTRON MICROSCOPIC STUDY OF THE PATTERNS OF EXTERNAL ROOT RESORPTION UNDER DIFFERENT CONDITIONS

    PubMed Central

    Sreeja, Ravindran; Minal, Chaudhary; Madhuri, Tumsare; Swati, Patil; Vijay, Wadhwan

    2009-01-01

    Objective: The aim of this study was to examine if there are qualitative differences in the appearance of external root resorption patterns of primary teeth undergoing physiologic resorption and permanent teeth undergoing pathological root resorption in different conditions. Material and Methods: A total of 40 teeth undergoing external root resorption in different conditions were divided into 4 groups and prepared for examination under scanning electron microscopy at magnifications ranging from 20x to 1000x. Group I: 10 primary molars exfoliated due to physiologic root resorption; Group II: 10 permanent teeth with periapical granulomas showing signs of resorption; Group III:10 permanent teeth therapeutically extracted during the course of orthodontic therapy with evidence of resorption, and Group IV: 10 permanent teeth associated with odontogenic tumors that showed evidence of resorption. Results: In Group I, the primary teeth undergoing resorption showed smooth extensive and predominantly regular areas reflecting the slow ongoing physiologic process. In Group II, the teeth with periapical granulomas showed the resorption was localized to apex with a funnel shaped appearance in most cases. Teeth in Group III, which had been subjected to a short period of light orthodontic force, showed the presence of numerous resorption craters with adjoining areas of cemental repair in some cases. Teeth associated with odontogenic tumors in Group IV showed many variations in the patterns of resorption with extensive loss of root length and a sharp cut appearance of the root in most cases. Conclusion: Differences were observed in the patterns of external root resorption among the studied groups of primary and permanent teeth under physiologic and pathological conditions. PMID:19936530

  6. Mitochondrial regulation of macrophage cholesterol homeostasis.

    PubMed

    Graham, Annette

    2015-12-01

    This review explores the relationship between mitochondrial structure and function in the regulation of macrophage cholesterol metabolism and proposes that mitochondrial dysfunction contributes to loss of the elegant homeostatic mechanisms which normally maintain cellular sterol levels within defined limits. Mitochondrial sterol 27-hydroxylase (CYP27A1) can generate oxysterol activators of liver X receptors which heterodimerise with retinoid X receptors, enhancing the transcription of ATP binding cassette transporters (ABCA1, ABCG1, and ABCG4), that can remove excess cholesterol via efflux to apolipoproteins A-1, E, and high density lipoprotein, and inhibit inflammation. The activity of CYP27A1 is regulated by the rate of supply of cholesterol substrate to the inner mitochondrial membrane, mediated by a complex of proteins. The precise identity of this dynamic complex remains controversial, even in steroidogenic tissues, but may include steroidogenic acute regulatory protein and the 18 kDa translocator protein, together with voltage-dependent anion channels, ATPase AAA domain containing protein 3A, and optic atrophy type 1 proteins. Certainly, overexpression of StAR and TSPO proteins can enhance macrophage cholesterol efflux to apoA-I and/or HDL, while perturbations in mitochondrial function, or changes in the expression of mitochondrial fusion proteins, alter the efficiency of cholesterol efflux. Molecules which can sustain or improve mitochondrial function or increase the activity of the protein complex involved in cholesterol transfer may have utility in resolving the problem of dysregulated macrophage cholesterol homeostasis, a condition which may contribute to inflammation, atherosclerosis, nonalcoholic steatohepatitis, osteoblastic bone resorption, and some disorders of the central nervous system.

  7. Dynamics of orthodontic root resorption and repair in human premolars: a light microscopy study.

    PubMed

    Winter, Björn U; Stenvik, Arild; Vandevska-Radunovic, Vaska

    2009-08-01

    The purpose of the study was to investigate the relationship between root resorption and repair in human premolars that had been orthodontically intruded. The objective was to examine these processes related to time and root development. Seventy-six premolars were divided into subgroups: 33 teeth were intruded and then extracted (G1); 25 teeth were intruded and then left in situ for varying periods before extraction (G2); 18 teeth served as the controls (G3). All teeth were examined by light microscopy. Using non-parametric statistical analysis, differences between the groups were examined with the Pearson chi-square test. Teeth in G1 and G2 had significantly more resorptive lesions, 55 and 64 per cent, respectively, than the controls of 11 per cent. Resorption was observed over the whole root surface and increased with time. The occurrence increased to 100 per cent in both experimental groups after 36 days of intrusion. The appearance of lesions in relation to root development showed no differences between G1 and G2. In the apical part of the root, total resorption of the dentine was sometimes observed, but no resorptions extended into the predentine. Resorptive lesions undergoing repair were seen in both groups, with significantly more repair in G2 (58 per cent) than in G1 (32 per cent). Active resorption and repair were sometimes seen at the same resorption site. Deposition of cellular and acellular cementum was found to the same extent over the whole root when repair took place. With time, resorption appeared over the whole root surface. In some teeth, resorptive activity continued up to 10 days after removal of forces but on the other hand, repair of the resorbed area sometimes started during active movement. The individual variation in repair was much wider compared with resorption. The predentine layer in the apical area appeared not to be affected by the resorptive process. PMID:19465737

  8. Management of external perforating root resorption by intentional replantation followed by Biodentine restoration.

    PubMed

    Pruthi, Preeti Jain; Dharmani, Umesh; Roongta, Ruchika; Talwar, Sangeeta

    2015-01-01

    Resorption of tooth structures can occur as a result of physiological, pathological, and idiopathic factors. Early diagnosis and appropriate treatment can prevent its serious complications. This case report presents surgical endodontic management of a trauma-induced perforating external root resorption, which was diagnosed with the help of cone beam computed tomography. Following root canal treatment, intentional replantation of the tooth was performed so as to expose the opening of the resorption defect to allow for complete debridement and closure. Eighteen months follow-up showed arrest of root resorption, and progressive healing of the defect.

  9. Management of external perforating root resorption by intentional replantation followed by Biodentine restoration

    PubMed Central

    Pruthi, Preeti Jain; Dharmani, Umesh; Roongta, Ruchika; Talwar, Sangeeta

    2015-01-01

    Resorption of tooth structures can occur as a result of physiological, pathological, and idiopathic factors. Early diagnosis and appropriate treatment can prevent its serious complications. This case report presents surgical endodontic management of a trauma-induced perforating external root resorption, which was diagnosed with the help of cone beam computed tomography. Following root canal treatment, intentional replantation of the tooth was performed so as to expose the opening of the resorption defect to allow for complete debridement and closure. Eighteen months follow-up showed arrest of root resorption, and progressive healing of the defect. PMID:26604965

  10. Biogeographic patterns of nutrient resorption from Quercus variabilis Blume leaves across China.

    PubMed

    Sun, X; Kang, H; Chen, H Y H; Björn, B; Samuel, B F; Liu, C

    2016-05-01

    The variation in nutrient resorption has been studied at different taxonomic levels and geographic ranges. However, the variable traits of nutrient resorption at the individual species level across its distribution are poorly understood. We examined the variability and environmental controls of leaf nutrient resorption of Quercus variabilis, a widely distributed species of important ecological and economic value in China. The mean resorption efficiency was highest for phosphorus (P), followed by potassium (K), nitrogen (N), sulphur (S), magnesium (Mg) and carbon (C). Resorption efficiencies and proficiencies were strongly affected by climate and respective nutrients concentrations in soils and green leaves, but had little association with leaf mass per area. Climate factors, especially growing season length, were dominant drivers of nutrient resorption efficiencies, except for C, which was strongly related to green leaf C status. In contrast, green leaf nutritional status was the primary controlling factor of leaf nutrient proficiencies, except for C. Resorption efficiencies of N, P, K and S increased significantly with latitude, and were negatively related to growing season length and mean annual temperature. In turn, N, P, K and S in senesced leaves decreased with latitude, likely due to their efficient resorption response to variation in climate, but increased for Mg and did not change for C. Our results indicate that the nutrient resorption efficiency and proficiency of Q. variabilis differed strongly among nutrients, as well as growing environments. Our findings provide important insights into understanding the nutrient conservation strategy at the individual species level and its possible influence on nutrient cycling.

  11. Molecular Aspects of Bone Resorption in β-Thalassemia Major

    PubMed Central

    Saki, Najmaldin; Abroun, Saeid; Salari, Fatemeh; Rahim, Fakher; Shahjahani, Mohammad; Javad, Mohammadi-Asl

    2015-01-01

    β-thalassemia is the most common single gene disorder worldwide, in which hemoglobin β-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes. PMID:26199898

  12. Equine Odontoclastic Tooth Resorption and Hypercementosis: Histopathologic Features.

    PubMed

    Smedley, R C; Earley, E T; Galloway, S S; Baratt, R M; Rawlinson, J E

    2015-09-01

    Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a painful progressive condition of older horses that involves multiple teeth, including canines and incisors. EOTRH is uncommonly recognized by veterinary pathologists and in some cases may be misdiagnosed as cementoblastoma. The cause is unknown. The goals of this study were to describe the histopathologic features of EOTRH in 17 affected horses from the United States and to increase awareness of this condition. Samples ranged from affected tooth to the entire rostral mandible and maxilla. Affected teeth exhibited cemental hyperplasia and lysis. The marked proliferation of cementum in severe cases caused bulbous enlargement of the intra-alveolar portions of affected teeth. Several teeth contained necrotic debris, bacteria, and plant material in the regions of cemental lysis. All horses exhibited dentinal lysis in at least affected tooth, and several contained necrotic debris in these regions. Endodontic disease was often present with inflammation, lysis, necrotic debris, fibrosis, and/or a thin rim of atubular mineralized tissue in the pulp cavity. Periodontal disease was a common feature that was primarily characterized by moderate lymphoplasmacytic inflammation. Resorption with secondary hypercementosis appears to begin on the external surface of the teeth rather than within the pulp cavity. Distinguishing EOTRH from other diseases requires a complete history that includes the number and location of affected teeth, a gross description of regional hard/soft tissue health, and radiographic findings.

  13. Reduction of precocious peri-implant resorption cone.

    PubMed

    De Santis, D; Zanotti, G; Morandini, S; Bordanzi, A; Gerosa, R; Rodella, L F; Rossetto, A; Chiarini, L; Nocini, P F; Bertossi, D

    2013-08-01

    Aim: After implant-insertion, bone tissue, newly-formed on peri-implant crest, undergoes to a mild marginal osseous readjustment due to build-up of inflammatory cell tissue (ICT). The present study verifies the possibility to limit bone resorption by placing implant fixtures 0.5 mm outside cortical bone edge. Methods: A clinically-controlled randomized study on 100 implants has been performed to compare early resorption process of implant fixtures placed 0.5 mm outside cortical bone edge with implant-fixtures inserted according to juxtacortical bone conventional protocols. Results: After 6 months, bone implant level was higher with emersion approach (-1.01±0.54 mm, mean±SD) than with submerged treatment (-1.56±0.5 mm) (P<0.001). Conclusion: Factors to achieve an excellent result at mean-long term seem to be very good, even though the latter have to be confirmed by follow-up.

  14. [The OPG/RANKL/RANK system and bone resorptive disease].

    PubMed

    Liu, Ji-Zhong; Ji, Zong-Ling; Chen, Su-Min

    2003-11-01

    The OPG/RANKL/RANK system plays an important role in osteoclastogenesis and represents a great progress in bone biology. RANKL, which expresses on the surface of osteoblast/stromal cells and activated T cells, binds to RANK on the osteoclastic precursors or mature osteoclasts, and promotes osteoclastogenesis and bone resorption. While osteoprotegerin (OPG), which is expressed by osteoblasts/stromal cells, strongly inhibits bone resorption by binding to its ligand RANKL and thereby blocks the interaction between BANKL and RANK. A number of cytokines and hormones exert their effects on bone metabolism by regulating the OPG/RANKL ratio in the bone marrow microenvironment. RANK is also expressed on mammary epithelial cells and RANKL expression in these cells is induced by pregnancy hormones, RANKL and RANK are essential for the formation of the lactating mammary gland and the transmission of maternal calcium to neonates in mammalian species. Modulation of these systems provides a unique opportunity to develop novel therapeutics to inhibit bone loss in osteoporosis, rheumatoid arthritis, and bone metastasis of cancer. Further research should be focused on the cooperation of OPG/RANKL/RANK system with other signal pathways and the interactions among bone remodeling, immune system and endocrinology system. Currently, the development of OPG analogues or compounds which may stimulate OPG expression is becoming an attractive industry which may be profitable to both patients and manufacturers. PMID:15971575

  15. Notch signaling promotes osteoclast maturation and resorptive activity.

    PubMed

    Ashley, Jason W; Ahn, Jaimo; Hankenson, Kurt D

    2015-11-01

    The role of Notch signaling in osteoclast differentiation is controversial with conflicting experimental evidence indicating both stimulatory and inhibitory roles. Differences in experimental protocols and in vivo versus in vitro models may explain the discrepancies between studies. In this study, we investigated cell autonomous roles of Notch signaling in osteoclast differentiation and function by altering Notch signaling during osteoclast differentiation using stimulation with immobilized ligands Jagged1 or Delta-like1 or by suppression with γ-secretase inhibitor DAPT or transcriptional inhibitor SAHM1. Stimulation of Notch signaling in committed osteoclast precursors resulted in larger osteoclasts with a greater number of nuclei and resorptive activity whereas suppression resulted in smaller osteoclasts with fewer nuclei and suppressed resorptive activity. Conversely, stimulation of Notch signaling in osteoclast precursors prior to induction of osteoclastogenesis resulted in fewer osteoclasts. Our data support a mechanism of context-specific Notch signaling effects wherein Notch stimulation inhibits commitment to osteoclast differentiation, but enhances the maturation and function of committed precursors.

  16. A rapid screening technique for feline odontoclastic resorptive lesions.

    PubMed

    Heaton, M; Wilkinson, J; Gorrel, C; Butterwick, R

    2004-12-01

    The feline odontoclastic resorptive lesion (FORL) status (presence or absence of odontoclastic resorptive lesions) of 423 clinically healthy cats was determined based on radiographic findings in a series of full mouth radiographs (eight views). This status was compared with the FORL status based on evaluation of only two views, namely the right and left mandibular premolar and molar views. Using the FORL status of the right and left third mandibular premolars (307 and 407) alone correctly predicted overall FORL status in 93.4 per cent of cats. The sensitivity of the new technique (FORL cases correctly diagnosed as positive by the test) was 78.5 per cent, while the negative predictive value (negative FORL cases correctly diagnosed by the test) was 91.3 per cent. Overall FORL status can therefore be confidently diagnosed in nine out of 10 cats by assessing FORL status in just two teeth (307 and 407) using two films, which has benefits for the cat (less anaesthetic time and reduced exposure to radiation) and the owner (reduced cost of screening). PMID:15600270

  17. Resorption kinetics of eggshell: an in vivo study.

    PubMed

    Dupoirieux, L; Pourquier, D; Neves, M; Téot, L

    2001-01-01

    Eggshell has been recently introduced as a bone substitute candidate in reconstructive surgery. The aim of this experimental study study was to determine its degradation rate in both a skeletal and extraskeletal site. In experiment 1, eggshell particles with four different sizes (50, 75, 150, and 300 microns in diameter) were implanted in subcutaneous pouches of 30 rats. In experiment 2, a fragment of ostrich eggshell was implanted on the nasal dorsum of 10 rats. Animals were sacrificed at 1 (N = 10), 2 (N = 10), and 4 months (N = 10) during the first stage of the study, and at 1 year during the second stage of the study. The results were assessed by X-ray examination and routine histological techniques. In experiment 1, all animals healed uneventfully. At 1 month, only 50-micron particles had undergone resorption. At 2 months, both 50- and 75-micron particles had undergone resorption. At 4 months, the 150- and 300-micron particles were resorbed incompletely. Histologically, the eggshell elicited a mild inflammatory reaction at 1 month that decreased progressively at further stages. In experiment 2, all animals except one healed uneventfully. Radiologically, the eggshell implant displayed a noticeable stability. Histologically, seven of nine implants were encapsulated, but two of them were surrounded by a bony rim. In conclusion, eggshell is a resorbable implant, but the degradation kinetic is size dependent. Large ostrich grafts are also suitable as onlay graft, but a complementary osteosynthesis is recommended to enhance osteointegration. PMID:11314188

  18. The effects of gallium nitrate on bone resorption.

    PubMed

    Bockman, Richard

    2003-04-01

    Gallium nitrate has been shown to be an effective treatment for patients with cancer-related hypercalcemia. Clinical studies have also suggested the drug may have considerably broader use in other diseases associated with accelerated bone loss including multiple myeloma, bone metastases, Paget's disease, and osteoporosis. The actions of gallium nitrate on bone are quite distinct from those of bisphosphonates. Preclinical studies show that gallium preferentially accumulates in trace amounts in metabolically active regions of bone. When present, gallium favorably alters the mineral properties to enhance hydroxyapatite crystallization and reduce mineral solubility. The drug also acts on the cellular components of bone to reduce bone resorption by decreasing acid secretion by osteoclasts. This effect appears to be mediated by inhibition of the ATPase-dependent proton pump of the osteoclast's ruffled membrane. Gallium does not inhibit the development or recruitment of osteoclasts to bone tissue, unlike many bisphosphonates that may induce osteoclast apoptosis. Together, these pharmacologic actions may yield a skeletal system with increased calcium and phosphate content and improved biomechanical strength. Gallium nitrate has potent antiresorptive effects on bone that can be achieved at considerably lower doses than are currently used for cancer-related hypercalcemia. Parenteral and oral formulations of gallium appear to have high activity in bone resorptive disorders, and thus development should be vigorously pursued in these diseases. PMID:12776254

  19. Role of interleukin 6 in epithelial hyperproliferation and bone resorption in middle ear cholesteatomas.

    PubMed

    Bujía, J; Kim, C; Ostos, P; Kastenbauer, E; Hültner, L

    1996-01-01

    Locally produced pro-inflammatory cytokines are considered to play an important role in the initiation and/or maintenance of inflammatory diseases. In cholesteatomatous lesions there are increased levels of some cytokines and inflammatory mediators like interleukin 1, tumor necrosis factor and colony-stimulating factor, etc. Interleukin 6 (IL-6) can be produced by different cells present in cholesteatoma (e.g. keratinocytes, lymphocytes, fibroblasts and macrophages). Until now, no data have been available on the role of IL-6 in cholesteatoma. In this study we used immunohistochemistry to investigate the presence and distribution of IL-6 in tissue samples from cholesteatoma patients. Levels of the cytokine were quantified in tissue extracts using an enzyme-linked immunosorbent assay. Finally, the presence of biologically active IL-6 was analyzed in the murine cell line 7TD1. Human skin samples obtained from the external ear canal were used as controls. Using the anti-IL-6 antibody in an alkaline phosphatase anti alkaline phosphatase technique, a moderate diffuse staining of the whole epidermis was observed in sections of normal skin. In cryostat sections of cholesteatoma samples, a stronger staining of the whole epithelium was observed. Many of the cells infiltrating the cholesteatoma stroma also showed positive immunostainings. The concentration of IL-6 in relation to the total protein concentration in cholesteatoma (119.33 +/- 30) were higher than in human skin (9.16 +/- 13). While IL-6 activity was not detected in skin samples, two of the ten cholesteatoma samples studied showed a stimulatory effect when incubated with the cell line 7TD1. The overexpression of IL-6 in middle ear cholesteatoma suggests a participation of this cytokine in some of the clinical features seen: epithelial hyperproliferation and bone resorption. The absence of biological activity in the majority of the cholesteatoma samples points to the presence of natural inhibitors for IL-6.

  20. Relationship between the Relative Limitation and Resorption Efficiency of Nitrogen vs Phosphorus in Woody Plants

    PubMed Central

    Han, Wenxuan; Tang, Luying; Chen, Yahan; Fang, Jingyun

    2013-01-01

    Most previous studies have ascribed variations in the resorption of a certain plant nutrient to its corresponding environmental availability or level in tissues, regardless of the other nutrients’ status. However, given that plant growth relies on both sufficient and balanced nutrient supply, the nutrient resorption process should not only be related to the absolute nutrient status, but also be regulated by the relative limitation of the nutrient. Here, based on a global woody-plants dataset from literature, we test the hypothesis that plants resorb proportionately more nitrogen (or phosphorus) when they are nitrogen (or phosphorus) limited, or similar proportions of nitrogen (N) and phosphorus (P) when co-limited by both nutrients (the relative resorption hypothesis). Using the N:P ratio in green foliage as an indicator of nutrient limitation, we found an inverse relationship between the difference in the proportionate resorption of N vs P and this foliar N:P ratio, consistent across species, growth-forms, and vegetation-types globally. Moreover, according to the relative resorption hypothesis, communities with higher/lower foliar N:P (more likely P/N limited) tend to produce litter with disproportionately higher/lower N:P, causing a worsening status of P/N availability; this positive feedback may somehow be counteracted by several negative-feedback mechanisms. Compared to N, P generally shows higher variability in resorption efficiency (proportion resorbed), and higher resorption sensitivity to nutrient availability, implying that the resorption of P seems more important for plant nutrient conservation and N:P stoichiometry. Our findings elucidate the nutrient limitation effects on resorption efficiency in woody plants at the global scale, and thus can improve the understanding of nutrient resorption process in plants. This study also suggests the importance of the foliar N:P ratio as a key parameter for biogeochemical modeling, and the relative resorption

  1. Relationship between the relative limitation and resorption efficiency of nitrogen vs phosphorus in woody plants.

    PubMed

    Han, Wenxuan; Tang, Luying; Chen, Yahan; Fang, Jingyun

    2013-01-01

    Most previous studies have ascribed variations in the resorption of a certain plant nutrient to its corresponding environmental availability or level in tissues, regardless of the other nutrients' status. However, given that plant growth relies on both sufficient and balanced nutrient supply, the nutrient resorption process should not only be related to the absolute nutrient status, but also be regulated by the relative limitation of the nutrient. Here, based on a global woody-plants dataset from literature, we test the hypothesis that plants resorb proportionately more nitrogen (or phosphorus) when they are nitrogen (or phosphorus) limited, or similar proportions of nitrogen (N) and phosphorus (P) when co-limited by both nutrients (the relative resorption hypothesis). Using the N:P ratio in green foliage as an indicator of nutrient limitation, we found an inverse relationship between the difference in the proportionate resorption of N vs P and this foliar N:P ratio, consistent across species, growth-forms, and vegetation-types globally. Moreover, according to the relative resorption hypothesis, communities with higher/lower foliar N:P (more likely P/N limited) tend to produce litter with disproportionately higher/lower N:P, causing a worsening status of P/N availability; this positive feedback may somehow be counteracted by several negative-feedback mechanisms. Compared to N, P generally shows higher variability in resorption efficiency (proportion resorbed), and higher resorption sensitivity to nutrient availability, implying that the resorption of P seems more important for plant nutrient conservation and N:P stoichiometry. Our findings elucidate the nutrient limitation effects on resorption efficiency in woody plants at the global scale, and thus can improve the understanding of nutrient resorption process in plants. This study also suggests the importance of the foliar N:P ratio as a key parameter for biogeochemical modeling, and the relative resorption

  2. Glutamine Modulates Macrophage Lipotoxicity

    PubMed Central

    He, Li; Weber, Kassandra J.; Schilling, Joel D.

    2016-01-01

    Obesity and diabetes are associated with excessive inflammation and impaired wound healing. Increasing evidence suggests that macrophage dysfunction is responsible for these inflammatory defects. In the setting of excess nutrients, particularly dietary saturated fatty acids (SFAs), activated macrophages develop lysosome dysfunction, which triggers activation of the NLRP3 inflammasome and cell death. The molecular pathways that connect lipid stress to lysosome pathology are not well understood, but may represent a viable target for therapy. Glutamine uptake is increased in activated macrophages leading us to hypothesize that in the context of excess lipids glutamine metabolism could overwhelm the mitochondria and promote the accumulation of toxic metabolites. To investigate this question we assessed macrophage lipotoxicity in the absence of glutamine using LPS-activated peritoneal macrophages exposed to the SFA palmitate. We found that glutamine deficiency reduced lipid induced lysosome dysfunction, inflammasome activation, and cell death. Under glutamine deficient conditions mTOR activation was decreased and autophagy was enhanced; however, autophagy was dispensable for the rescue phenotype. Rather, glutamine deficiency prevented the suppressive effect of the SFA palmitate on mitochondrial respiration and this phenotype was associated with protection from macrophage cell death. Together, these findings reveal that crosstalk between activation-induced metabolic reprogramming and the nutrient microenvironment can dramatically alter macrophage responses to inflammatory stimuli. PMID:27077881

  3. Growth regulation by macrophages

    SciTech Connect

    Wharton, W.; Walker, E.; Stewart, C.C.

    1982-01-01

    The evidence reviewed here indicates that macrophages, either acting alone or in concert with other cells, influence the proliferation of multiple types of cells. Most of the data indicate that these effects are mediated by soluble macrophage-elaborated products (probably proteins) although the role of direct cell-to-cell contacts cannot be ruled out in all cases. A degree of success has been achieved on the biochemical characterization of these factors, due mainly to their low specific activity in conditioned medium and the lack of rapid, specific assays. Understanding the growth-regulating potential of macrophages is an important and needed area of research.

  4. Echistatin is a potent inhibitor of bone resorption in culture.

    PubMed

    Sato, M; Sardana, M K; Grasser, W A; Garsky, V M; Murray, J M; Gould, R J

    1990-10-01

    The venom protein, s-echistatin, originally derived from the saw-scaled viper Echis carinatus, was found to be a potent inhibitor of bone resorption by isolated osteoclasts. This Arg24-Gly25-Asp26-(RGD)-containing protein inhibited the excavation of bone slices by rat osteoclasts (IC50 = 0.1 nM). It also inhibited the release of [3H]proline from labeled bone particles by chicken osteoclasts (IC50 = 100 nM). By comparison, the tetrapeptide Arg-Gly-Asp-Ser (RGDS) inhibited resorption by rat or chicken osteoclasts with an IC50 of 0.1 mM while ala24-echistatin was inactive. Video microscopy showed that rat osteoclast attachment to substrate was more sensitive to s-echistatin than was the attachment of mononuclear cells or chicken osteoclasts. The difference in sensitivity of rat and chicken osteoclasts to s-echistatin may be due to differences between receptors on rat and chicken osteoclasts for s-echistatin. Antibody localization of echistatin on these cells showed much greater echistatin binding to rat osteoclasts than to chicken osteoclasts. Laser scanning confocal microscopy after immunohistochemical staining showed that s-echistatin binds to osteoclasts, that s-echistatin receptors are most abundant at the osteoclast/glass interface, and that s-echistatin colocalizes with vinculin. Confocal interference reflection microscopy of osteoclasts incubated with s-echistatin, demonstrated colocalization of s-echistatin with the outer edges of clusters of grey contacts at the tips of some lamellipodia. Identification of the echistatin receptor as an integrin was confirmed by colocalization of echistatin fluorescence with staining for an alpha-like subunit. Attachment of bone particles labeled with [3H]proline to chicken osteoclasts confirmed that the mechanism of action of echistatin was to inhibit osteoclast binding to bone presumably by disrupting adhesion structures. These data demonstrate that osteoclasts bind to bone via an RGD-sequence as an obligatory step in bone

  5. Management of a Large Internal Resorption Lesion with Metal Reinforced Glass Ionomer Cement

    PubMed Central

    Bhuyan, Atool Chandra; Arora, Suraj; Sethi, Kunal; Kalra, Tarun

    2014-01-01

    Mineral trioxide aggregate is the mainstay of treatment of large internal resorption defects. But its cost may be a deterrent to its use in some patients. The present case report describes the successful endodontic management of an extensive internal resorptive lesion in a mandibular molar with metal reinforced glass ionomer cement. PMID:25436156

  6. Residual ridge resorption, lower denture stability and subjective complaints among edentulous individuals.

    PubMed

    Huumonen, S; Haikola, B; Oikarinen, K; Söderholm, A-L; Remes-Lyly, T; Sipilä, K

    2012-05-01

    Residual ridge resorption in the mandible after tooth loss may lead to worsening of complete denture stability and to various subjective complaints. The aim was to evaluate the association between radiologically assessed residual ridge resorption in the mandible, clinically assessed stability of lower complete denture and subjective complaints among elderly denture wearers. The study population consisted of 326 (115 men and 211 women) edentulous subjects aged 60-78years, all of whom were wearing complete dentures in the mandible. Data on subjective complaints were obtained from questionnaires and interviews. Denture stability was assessed clinically. Residual ridge resorption was analysed from panoramic radiographs. The results showed that women were significantly more often satisfied with their lower dentures and reported fewer problems with eating than men. They also had significantly more often residual ridge resorption than men. Among women, residual ridge resorption was significantly associated with poor chewing ability, low satisfaction with dentures and poor denture stability. Among men, residual ridge resorption did not associate with subjective complaints or denture stability. Poor satisfaction with dentures associated significantly with poor denture stability in both genders. In conclusion, these results highlight the importance of denture maintenance treatment. As the extent of residual ridge resorption in the mandible was the most important factor that increased dissatisfaction with lower complete dentures, it is also important to inhibit the progression of resorption by preventing tooth loss or by using implant-retained dentures.

  7. Nitrogen and phosphorus resorption in a neotropical rain forest of a nutrient-rich soil.

    PubMed

    Martínez-Sánchez, José Luis

    2005-01-01

    In tropical forests with nutrient-rich soil tree's nutrient resorption from senesced leaves has not always been observed to be low. Perhaps this lack of consistence is partly owing to the nutrient resorption methods used. The aim of the study was to analyse N and P resorption proficiency from tropical rain forest trees in a nutrient-rich soil. It was hypothesised that trees would exhibit low nutrient resorption in a nutrient-rich soil. The soil concentrations of total N and extractable P, among other physical and chemical characteristics, were analysed in 30 samples in the soil surface (10 cm) of three undisturbed forest plots at 'Estaci6n de Biologia Los Tuxtlas' on the east coast of Mexico (18 degrees 34' - 18 degrees 36' N, 95 degrees 04' - 95 degrees 09' W). N and P resorption proficiency were determined from senescing leaves in 11 dominant tree species. Nitrogen was analysed by microkjeldahl digestion with sulphuric acid and distilled with boric acid, and phosphorus was analysed by digestion with nitric acid and perchloric acid. Soil was rich in total N (0.50%, n = 30) and extractable P (4.11 microg g(-1) n = 30). As expected, trees showed incomplete N (1.13%, n = 11) and P (0.11%, n = 1) resorption. With a more accurate method of nutrient resorption assessment, it is possible to prove that a forest community with a nutrient-rich soil can have low levels of N and P resorption.

  8. Fingolimod suppresses bone resorption in female patients with multiple sclerosis.

    PubMed

    Miyazaki, Yusei; Niino, Masaaki; Kanazawa, Ippei; Suzuki, Masako; Mizuno, Masanori; Hisahara, Shin; Fukazawa, Toshiyuki; Takahashi, Eri; Amino, Itaru; Ochi, Ryutaro; Nakamura, Masakazu; Akimoto, Sachiko; Minami, Naoya; Fujiki, Naoto; Doi, Shizuki; Shimohama, Shun; Terayama, Yasuo; Kikuchi, Seiji

    2016-09-15

    Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the inflammatory activity of multiple sclerosis (MS), and has been shown to suppress osteoporosis in mouse models. In this study, levels of bone turnover markers were quantified in serum and urine samples from MS patients treated with fingolimod. Compared with untreated MS patients and healthy controls, fingolimod-treated MS patients had a significantly lower level of the bone resorption marker type I collagen cross-linked N-telopeptide in urine. This finding was prominent in female but was not seen in male subjects. Our results suggest that fingolimod may have a beneficial effect on bone mass loss in female MS patients. PMID:27609272

  9. The Majority of Resorptions in Old Mice Are Euploid

    PubMed Central

    Tao, Yong; Liu, X. Johné

    2015-01-01

    Chromosomal abnormality is a leading cause of aging-related infertility, spontaneous abortion and congenital birth defects in humans. Karyotype analyses of spontaneously aborted human fetuses reveal high proportions (~50%) being chromosomal abnormal with the majority being trisomies of various chromosomes. As a model organism, mice are widely used for studies of reproduction and reproductive aging. Like older women, older mice exhibit high incidences of early embryo death. However, it is not known if aneuploidy is prevalent amongst resorptions in older mice. We have karyotyped 65 retarded/resorbed fetuses in 10-month-old C57BL/6 mice, and found that 55 (84.6%±8.8%, with 95% confidence) were euploid. Similarly, of 40 such fetuses from 17 month-old C57BL/6 mice, we found 38 (95±7%, with 95% confidence 95%) being euploid. Therefore, aneuploidy is not a leading cause of embryo death in older mice. PMID:26636341

  10. Management of Inflammatory Internal Root Resorption with Biodentine and Thermoplasticised Gutta-Percha.

    PubMed

    Umashetty, Girish; Hoshing, Upendra; Patil, Suvarna; Ajgaonkar, Nishant

    2015-01-01

    Internal root resorption is a chronic inflammatory process initiated within the pulp space with the loss of dentin. This condition demands a comprehensive understanding of the pathologic process, so as to identify the cause and arrest the resorptive phenomena. It is a rare occurrence, asymptomatic, with slow progression, detected through routine radiographic examination, where it appears as a radiolucent lesion. This paper reports a clinical case of inflammatory internal root resorption in the premolar tooth. Because it is asymptomatic, internal root resorption needs an early diagnosis in order to institute the endodontic treatment before the process compromises the remaining mineralized structures of the tooth. Biodentine was used to reinforce the weaker structures in the root. Thermoplasticised gutta-percha was used to completely obturate the defect. Ten-month follow-up showed arrest of internal root resorption.

  11. Management of Inflammatory Internal Root Resorption with Biodentine and Thermoplasticised Gutta-Percha

    PubMed Central

    Umashetty, Girish; Hoshing, Upendra; Patil, Suvarna; Ajgaonkar, Nishant

    2015-01-01

    Internal root resorption is a chronic inflammatory process initiated within the pulp space with the loss of dentin. This condition demands a comprehensive understanding of the pathologic process, so as to identify the cause and arrest the resorptive phenomena. It is a rare occurrence, asymptomatic, with slow progression, detected through routine radiographic examination, where it appears as a radiolucent lesion. This paper reports a clinical case of inflammatory internal root resorption in the premolar tooth. Because it is asymptomatic, internal root resorption needs an early diagnosis in order to institute the endodontic treatment before the process compromises the remaining mineralized structures of the tooth. Biodentine was used to reinforce the weaker structures in the root. Thermoplasticised gutta-percha was used to completely obturate the defect. Ten-month follow-up showed arrest of internal root resorption. PMID:26579316

  12. Patterns in foliar nutrient resorption stoichiometry at multiple scales: controlling factors and ecosystem consequences (Invited)

    NASA Astrophysics Data System (ADS)

    Reed, S.; Cleveland, C. C.; Davidson, E. A.; Townsend, A. R.

    2013-12-01

    During leaf senescence, nutrient rich compounds are transported to other parts of the plant and this 'resorption' recycles nutrients for future growth, reducing losses of potentially limiting nutrients. Variations in leaf chemistry resulting from nutrient resorption also directly affect litter quality, in turn, regulating decomposition rates and soil nutrient availability. Here we investigated stoichiometric patterns of nitrogen (N) and phosphorus (P) resorption efficiency at multiple spatial scales. First, we assembled a global database to explore nutrient resorption among and within biomes and to examine potential relationships between resorption stoichiometry and ecosystem nutrient status. Next, we used a forest regeneration chronosequence in Brazil to assess how resorption stoichiometry linked with a suite of other nutrient cycling measures and with ideas of how nutrient limitation may change over secondary forest regrowth. Finally, we measured N:P resorption ratios of six canopy tree species in a Costa Rican tropical forest. We calculated species-specific resorption ratios and compared them with patterns in leaf litter and topsoil nutrient concentrations. At the global scale, N:P resorption ratios increased with latitude and decreased with mean annual temperature (MAT) and precipitation (MAP; P<0.001 for each). In particular, we observed a notable switch across latitudes: N:P resorption ratios were generally <1 in latitudes <23° and >1 in latitudes >23°. Focusing on tropical sites in our global dataset we found that, despite fewer data and a restricted latitudinal range, a significant relationship between latitude and N:P resorption ratios persisted (P<0.001). In contrast, tropical N:P resorption ratios did not vary with MAT (P=0.965) and the relationship with MAP was only marginally significant (P=0.089). Data suggest that soil type, at least in part, helps explain N:P resorption patterns across tropical latitudes: plants on more weathered soils (Oxisols

  13. Management of External Invasive Cervical Resorption Tooth with Mineral Trioxide Aggregate: A Case Report

    PubMed Central

    Ikhar, Anuja; Thakur, Nikita; Patel, Aditya; Bhede, Rohan; Patil, Pranav; Gupta, Surbhi

    2013-01-01

    Invasive cervical resorption is entirely uncommon entities and the etiology is poorly understood. A 19 year old patient presented with fractured upper left central incisor and sinus tract opening on the distobuccal aspect in cervical region. Radiographic examination shows irregular radiolucency over the coronal one-third and it extended externally towards the external invasive resorption. After sectional obturation, the defect was accessed surgically. The resorption area was chemomechanically debrided using irrigant solution. Fibre post placement using flowable composite resin and Mineral Trioxide Aggregate (MTA) was used to fill the resorptive defect, and the coronal access was temporarily sealed. Composite restoration was subsequently replaced with ceramic crown after 4 years. Radiographs at 1 and 4 years showed adequate repair of the resorption and endodontic success. Clinically and radiographically the tooth was asymptomatic, and no periodontal pocket was found after a 4-year followup. PMID:23476658

  14. Tissue-resident macrophages

    PubMed Central

    Davies, Luke C.; Jenkins, Stephen J.; Allen, Judith E.; Taylor, Philip R.

    2014-01-01

    Tissue-resident macrophages are a heterogeneous population of immune cells that fulfill tissue-specific and niche-specific functions. These range from dedicated homeostatic functions, such as clearance of cellular debris and iron processing, to central roles in tissue immune-surveillance, response to infection and the resolution of inflammation. Recent studies highlight marked heterogeneity in the origins of tissue macrophages that arise from hematopoietic versus self-renewing embryo-derived populations. We discuss the tissue–niche-specific factors that dictate cell phenotype, the definition of which will allow novel strategies to promote the restoration of tissue homeostasis. Understanding the mechanisms that dictate tissue macrophage heterogeneity should explain why simplified paradigms of macrophage activation do not explain the extent of heterogeneity seen in vivo. PMID:24048120

  15. Nutrient limitation results in juvenile hormone-mediated resorption of previtellogenic ovarian follicles in mosquitoes

    PubMed Central

    Clifton, Mark E.; Noriega, Fernando G.

    2011-01-01

    Juvenile hormone (JH) is a central hormonal regulator of previtellogenic development in female Aedes aegypti mosquitoes. JH levels are low at eclosion and increase during the first day after adult emergence. This initial rise in JH is essential for female reproductive maturation. After previtellogenic maturation is complete, the mosquito enters a ‘state-of-arrest’ during which JH synthesis continues at a slower pace and further ovary development is repressed until a blood meal is taken. By examining the relationships between juvenile hormone, follicular resorption and nutrition in A. aegypti, we were able to define a critical role of JH during the previtellogenic resting stage. The rate of follicular resorption in resting stage mosquitoes is dependent on nutritional quality. Feeding water alone caused the rate of follicular resorption to reach over 20% by day 7 after emergence. Conversely, feeding a 20% sucrose solution caused resorption to remain below 5% during the entire experimental period. Mosquitoes fed 3% sucrose show rates of resorption intermediate between water and 20% sucrose and only reached 10% by day 7 after emergence. Follicular resorption is related to JH levels. Ligated abdomens separated from a source of JH (the corpora allata) showed an increase in resorption comparable to similarly aged starved mosquitoes (16%). Resorption in ligated abdomens was reduced to 6% by application of methoprene. The application of methoprene was also sufficient to prevent resorption in intact mosquitoes starved for 48 hours (14% starved vs. 4% starved with methoprene). Additionally, active caspases were localized to resorbing follicles indicating that an apoptotic cell-death mechanism is responsible for follicular resorption during the previtellogenic resting stage. Taken together, these results indicate that JH mediates reproductive trade-offs in resting stage mosquitoes in response to nutrition. PMID:21708165

  16. The Elusive Antifibrotic Macrophage

    PubMed Central

    Adhyatmika, Adhyatmika; Putri, Kurnia S. S.; Beljaars, Leonie; Melgert, Barbro N.

    2015-01-01

    Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs, account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM) proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e., antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behavior-stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behavior in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review, we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behavior. PMID:26618160

  17. Macrophage polarization in inflammatory diseases.

    PubMed

    Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

    2014-01-01

    Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.

  18. Biogeographic patterns of nutrient resorption from Quercus variabilis Blume leaves across China.

    PubMed

    Sun, X; Kang, H; Chen, H Y H; Björn, B; Samuel, B F; Liu, C

    2016-05-01

    The variation in nutrient resorption has been studied at different taxonomic levels and geographic ranges. However, the variable traits of nutrient resorption at the individual species level across its distribution are poorly understood. We examined the variability and environmental controls of leaf nutrient resorption of Quercus variabilis, a widely distributed species of important ecological and economic value in China. The mean resorption efficiency was highest for phosphorus (P), followed by potassium (K), nitrogen (N), sulphur (S), magnesium (Mg) and carbon (C). Resorption efficiencies and proficiencies were strongly affected by climate and respective nutrients concentrations in soils and green leaves, but had little association with leaf mass per area. Climate factors, especially growing season length, were dominant drivers of nutrient resorption efficiencies, except for C, which was strongly related to green leaf C status. In contrast, green leaf nutritional status was the primary controlling factor of leaf nutrient proficiencies, except for C. Resorption efficiencies of N, P, K and S increased significantly with latitude, and were negatively related to growing season length and mean annual temperature. In turn, N, P, K and S in senesced leaves decreased with latitude, likely due to their efficient resorption response to variation in climate, but increased for Mg and did not change for C. Our results indicate that the nutrient resorption efficiency and proficiency of Q. variabilis differed strongly among nutrients, as well as growing environments. Our findings provide important insights into understanding the nutrient conservation strategy at the individual species level and its possible influence on nutrient cycling. PMID:26597338

  19. Relationship between dental anomalies and orthodontic root resorption of upper incisors.

    PubMed

    Van Parys, Katrien; Aartman, Irene H A; Kuitert, Reinder; Zentner, Andrej

    2012-10-01

    The aim of this study was to examine the potential relationship between the occurrence of orthodontic root resorption and presence of dental anomalies such as tooth agenesis and pipette-shaped roots. Dental anomalies and root resorption were assessed on dental panoramic tomographs (DPT) of 88 subjects, 27 males and 61 females, mean age 28.4 (SD = 11.3 years), selected from orthodontic patients on the basis of the following exclusion criteria: previous fixed appliance treatment, bad quality of the DPTs and no visibility of the periodontal ligament of every tooth, and younger than 15 years of age at the onset of treatment with fixed edgewise appliance lasting at least 18 months. A pipette-shaped root was identified as defined by a drawing. Tooth agenesis was assessed on DPTs and from subjects' dental history. Root resorption was calculated as the difference between the root length before and after treatment, with and without a correction factor (crown length post-treatment/crown length pre-treatment). If one of the four upper incisors showed root resorption of ≥2.3 mm with both formulas, the patient was scored as having root resorption. Chi-square tests indicated that there was no relationship between orthodontic root resorption and agenesis (P = 0.885) nor between orthodontic root resorption and pipette-shaped roots (P = 0.800). There was no relationship between having one of the anomalies and root resorption either (P = 0.750). In the present study, it was not possible to confirm on DPTs a relationship between orthodontic root resorption and dental anomalies, such as agenesis and pipette-shaped roots.

  20. Biphasic influence of PGE2 on the resorption activity of osteoclast-like cells derived from human peripheral blood monocytes and mouse RAW264.7 cells.

    PubMed

    Lutter, Anne-Helen; Hempel, Ute; Anderer, Ursula; Dieter, Peter

    2016-08-01

    Osteoclasts are large bone-resorbing cells of hematopoietic origin. Their main function is to dissolve the inorganic component hydroxyapatite and to degrade the organic bone matrix. Prostaglandin E2 (PGE2) indirectly affects osteoclasts by stimulating osteoblasts to release factors that influence osteoclast activity. The direct effect of PGE2 on osteoclasts is still controversial. To study the influence of PGE2 on osteoclast activity, human peripheral blood monocytes (hPBMC) and mouse RAW264.7 cells were cultured on osteoblast-derived extracellular matrix. hPBMC and RAW264.7 cells were differentiated by the addition of macrophage colony-stimulation factor and receptor activator of NFκB ligand and treated with PGE2 before and after differentiation induction. The pit area, an indicator of resorption activity, and the activity of tartrate-resistant acid phosphatase were dose-dependently inhibited when PGE2 was present ab initio, whereas the resorption activity remained unchanged when the cells were exposed to PGE2 from day 4 of culture. These results lead to the conclusion that PGE2 treatment inhibits only the differentiation of precursor osteoclasts whereas differentiated osteoclasts are not affected. PMID:27499447

  1. Macrophages and Iron Metabolism.

    PubMed

    Soares, Miguel P; Hamza, Iqbal

    2016-03-15

    Iron is a transition metal that due to its inherent ability to exchange electrons with a variety of molecules is essential to support life. In mammals, iron exists mostly in the form of heme, enclosed within an organic protoporphyrin ring and functioning primarily as a prosthetic group in proteins. Paradoxically, free iron also has the potential to become cytotoxic when electron exchange with oxygen is unrestricted and catalyzes the production of reactive oxygen species. These biological properties demand that iron metabolism is tightly regulated such that iron is available for core biological functions while preventing its cytotoxic effects. Macrophages play a central role in establishing this delicate balance. Here, we review the impact of macrophages on heme-iron metabolism and, reciprocally, how heme-iron modulates macrophage function.

  2. [Macrophages in asthma].

    PubMed

    Medina Avalos, M A; Orea Solano, M

    1997-01-01

    Every time they exist more demonstrations of the paper than performs the line monocytes-macrophage in the patogenesis of the bronchial asthma. The mononuclear phagocytes cells, as the alveolar macrophages, also they can be activated during allergic methods. The monocytes macrophages are possible efficient inductors of the inflammation; this due to the fact that they can secrete inflammatory mediators, between those which are counted the pre-forming granules of peptides, metabolites of oxidation activation, activator of platelets activator and metabolites of the arachidonic acid. The identification of IL-1 in the liquidate of the bronchial ablution of sick asthmatic, as well as the identification of IL-1 in the I bronchioalveolar washing of places of allergens cutaneous prick, supports the activation concept mononuclear of phagocytic cells in allergic sufferings. PMID:9432275

  3. Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice.

    PubMed

    Katsumata, Shinichi; Wolber, Frances M; Tadaishi, Miki; Tousen, Yuko; Ishimi, Yoshiko; Kruger, Marlena C

    2015-01-01

    Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice.

  4. Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice.

    PubMed

    Katsumata, Shinichi; Wolber, Frances M; Tadaishi, Miki; Tousen, Yuko; Ishimi, Yoshiko; Kruger, Marlena C

    2015-01-01

    Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice. PMID:26440641

  5. Comparative effects of five bisphosphonates on apoptosis of macrophage cells in vitro.

    PubMed

    Moreau, M F; Guillet, C; Massin, P; Chevalier, S; Gascan, H; Baslé, M F; Chappard, D

    2007-03-01

    Bisphosphonates (BPs) inhibits bone resorption by reducing osteoclastic activity; they induce osteoclast apoptosis. Pathophysiology of prostheses loosening is complex and implies an inflammatory reaction secondary to the phagocytosis of wear debris by macrophages with a secondary increased bone resorption by osteoclasts. BPs inhibit proliferation and cause cell death in macrophages by induction of apoptosis. We have used mouse macrophage-like J774.1 cells to evaluate the effects of five BPs. J774A.1 cells were cultured in a standard culture medium for 2-days. BPs (alendronate, pamidronate, etidronate, risedronate, zoledronic acid) were added in the medium at concentration of 10(-6) to 10(-4)M during 3 days. Cells were studied by fluorescence microscopy after staining with the fluorescent dye Hoescht H33342 and the percentage of apoptotic cells was determined on 300 nuclei. Cells were analyzed by flow cytofluorometry after staining with annexin V-FITC (for counting apoptotic cells) and propidium iodide (for necrotic/late-apoptotic cells) on 2000 cells. Etidronate did not cause significant apoptosis or necrosis, at any concentration. Alendronate and pamidronate caused apoptosis and death only at very high concentration [10(-4)M]. On the contrary, apoptotic and necrotic cells were evidenced with risedronate or zoledronic acid at lower concentrations. These effects were dose-dependant and occurred when concentration reached [10(-5)M]. The number of apoptotic cells was higher with zoledronic acid and then with risedronate. Cytofluorometry appeared superior to cytologic analysis in the investigation of macrophage apoptosis, since necrotic cells loose contact with the glass slides and are not identifiable in cytological counts. Some amino-BPs appear to induce apoptosis in macrophages. PMID:17157266

  6. Nonsurgical Endodontic Retreatment of Advanced Inflammatory External Root Resorption Using Mineral Trioxide Aggregate Obturation

    PubMed Central

    Utneja, Shivani; Garg, Gaurav; Arora, Shipra; Talwar, Sangeeta

    2012-01-01

    Inflammatory external root resorption is one of the major complications after traumatic dental injury. In this case report, we describe treatment of a maxillary central incisor affected by severe, perforating external root resorption. An 18-year-old patient presented with a previously traumatized, root-filled maxillary central incisor associated with pain and sinus tract. Radiographic examination revealed periradicular lesion involving pathologic resorption of the apical region of the root and lateral root surface both mesially and distally. After removal of the root canal filling, the tooth was disinfected with intracanal triple antibiotic paste for 2 weeks. The antibiotic dressing was then removed, and the entire root canal was filled with mineral trioxide aggregate. The endodontic access cavity was restored with composite resin. After 18 months, significant osseous healing of the periradicular region and lateral periodontium had occurred with arrest of external root resorption, and no clinical symptoms were apparent. PMID:23304567

  7. Response of Bone Resorption Markers to Aristolochia longa Intake by Algerian Breast Cancer Postmenopausal Women

    PubMed Central

    Benarba, Bachir; Meddah, Boumedienne; Tir Touil, Aicha

    2014-01-01

    Aristolochia longa is widely used in traditional medicine in Algeria to treat breast cancer. The aim of the present study was to investigate the response of bone resorption markers to A. longa intake by Algerian breast cancer postmenopausal women. According to the A. longa intake, breast cancer patients were grouped into A. longa group (Al) (n = 54) and non-A. longa group (non-Al) (n = 24). 32 women constituted the control group. Bone resorption markers (from urine) pyridinoline (PYD) and deoxypyridinoline (DPD) were determined by HPLC. Serum and urinary creatinine, uric acid, and urea were measured. 1 g of A. longa intake resulted in significant rise of renal serum markers and a pronounced increase of bone resorption markers. The intake of A. longa roots is detrimental for kidney function and resulted in high bone resorption, maybe due to the reduction in renal function caused by the aristolochic acids contained in the roots. PMID:24876833

  8. Evidence for multiple bone resorption-stimulating factors produced by normal human keratinocytes in culture.

    PubMed

    Fried, R M; Voelkel, E F; Rice, R H; Levine, L; Tashjian, A H

    1988-06-01

    Conditioned medium from cultured normal human foreskin keratinocytes enhanced the release of calcium from neonatal mouse calvaria in organ culture. Unfractionated keratinocyte-conditioned medium (KCM) stimulated bone resorption in a dose-dependent manner, but it did not increase the concentration of prostaglandin E2 (PGE2) in the bone culture medium until a maximal dose of KCM for resorption was used. Furthermore, inhibitors of PGE2 synthesis, indomethacin, ibuprofen, and piroxicam, did not inhibit KCM-induced calcium release. High concentrations of KCM increased cAMP production by calvaria in the presence of isobutylmethylxanthine, but the increase was small compared with that produced by a dose of bovine PTH that caused a similar level of bone resorption. The bone resorption-stimulating activity of KCM was not lost after incubation at 56 C for 60 min, but it was lost after heating at 100 C for 10 min. Fractionation of KCM by gel filtration chromatography revealed two distinct peaks of bone resorption-stimulating activity. One peak, KCMI, caused a significant increase in bone resorption at 2 micrograms protein/ml. KCMI did not increase medium PGE2, and inhibition of PGE2 synthesis in bone had no effect on KCMI-induced bone resorption. KCMI failed to increase cAMP production by human osteosarcoma SaOS-2 cells. Another peak, KCMII, caused a dose-dependent increase in bone resorption, and a significant increase in medium calcium was noted at a 20-fold lower concentration (0.1 microgram protein/ml) than with KCMI. In contrast to KCMI, the increase in bone resorption stimulated by KCMII was accompanied by a parallel increase in the production of PGE2, and inhibition of PGE2 synthesis completely inhibited the bone resorption-stimulating activity of KCMII. KCMII also caused an increase in cAMP production by SaOS-2 cells. We conclude that KCM contains at least two distinct bone resorption-stimulating factors, one of which acts via a PG-mediated mechanism and the other by

  9. Convergent responses of nitrogen and phosphorus resorption to nitrogen inputs in a semiarid grassland

    USGS Publications Warehouse

    Lü, Xiao-Tao; Reed, Sasha; Yu, Qiang; He, Nian-Peng; Wang, Zheng-Wen; Han, Xing-Guo

    2013-01-01

    Human activities have significantly altered nitrogen (N) availability in most terrestrial ecosystems, with consequences for community composition and ecosystem functioning. Although studies of how changes in N availability affect biodiversity and community composition are relatively common, much less remains known about the effects of N inputs on the coupled biogeochemical cycling of N and phosphorus (P), and still fewer data exist regarding how increased N inputs affect the internal cycling of these two elements in plants. Nutrient resorption is an important driver of plant nutrient economies and of the quality of litter plants produce. Accordingly, resorption patterns have marked ecological implications for plant population and community fitness, as well as for ecosystem nutrient cycling. In a semiarid grassland in northern China, we studied the effects of a wide range of N inputs on foliar nutrient resorption of two dominant grasses, Leymus chinensis and Stipa grandis. After 4 years of treatments, N and P availability in soil and N and P concentrations in green and senesced grass leaves increased with increasing rates of N addition. Foliar N and P resorption significantly decreased along the N addition gradient, implying a resorption-mediated, positive plant–soil feedback induced by N inputs. Furthermore, N : P resorption ratios were negatively correlated with the rates of N addition, indicating the sensitivity of plant N and P stoichiometry to N inputs. Taken together, the results demonstrate that N additions accelerate ecosystem uptake and turnover of both N and P in the temperate steppe and that N and P cycles are coupled in dynamic ways. The convergence of N and P resorption in response to N inputs emphasizes the importance of nutrient resorption as a pathway by which plants and ecosystems adjust in the face of increasing N availability.

  10. Condylar resorption following temporomandibular joint arthroscopy in a patient with essential thrombocythemia.

    PubMed

    Balasubramaniam, Ramesh; Van Sickels, Joseph; Falace, Donald

    2006-05-01

    Condylar resorption of the temporomandibular joint (TMJ) is a poorly understood phenomenon that is the subject of much controversy. The following case report depicts a unique case of condylar resorption (CR) in a 49-year-old female patient with essential thrombocythemia who underwent arthrocentesis of the TMJ. The exact cause of the CR is unclear but it is speculated that it was likely due to hemorrhagic and thrombotic complications during surgery secondary to an elevated platelet count. PMID:16632268

  11. Scanning electron microscopy reveals severe external root resorption in the large periapical lesion.

    PubMed

    Ookubo, Kensuke; Ookubo, Atsushi; Tsujimoto, Masaki; Sugimoto, Kouji; Yamada, Shizuka; Hayashi, Yoshihiko

    2016-06-01

    The present study was designed to investigate the relationships between clinicopathological findings and the resorptive conditions of root apices of teeth with periodontitis. The samples included 21 root apices with large periapical radiolucent lesions. The preoperative computed tomography (CT) and intraoperative findings were correlated with the presence, extension, and the progression pattern of periapical resorption using a scanning electron microscope. The subjects' age, gender, chief complaint, type of tooth, percussion test results, size of periapical lesion using CT, and intraoperative findings were recorded. All apicoectomies were performed under an operative microscope for endodontic microsurgery. A significant large size was observed in cystic lesions compared with granulomatous lesions. The cementum surface at the periphery of the lesion was covered with globular structures (2-3 μm in diameter). Cementum resorption started as small defect formations at the surface. As the defect formation progressed, a lamellar structure appeared at the resorption area, and the size of globular structures became smaller than that of globules at the surface. Further resorption produced typical lacuna formation, which was particularly observed in fracture cases. The most morphologically severe destructive pattern of dentin resorption was observed in large cystic lesions. This study is the first report to elucidate the relationships between three clinical types of undesirable periapical lesions: (1) undertreatment, (2) periapical fracture, (3) macro-level resorption, and the microstructure of external root resorption including from small defects at the cementum surface to a significant destructive pattern inside the dentin. Microsc. Res. Tech. 79:495-500, 2016. © 2016 Wiley Periodicals, Inc. PMID:26957368

  12. Convergent responses of nitrogen and phosphorus resorption to nitrogen inputs in a semiarid grassland.

    PubMed

    Lü, Xiao-Tao; Reed, Sasha; Yu, Qiang; He, Nian-Peng; Wang, Zheng-Wen; Han, Xing-Guo

    2013-09-01

    Human activities have significantly altered nitrogen (N) availability in most terrestrial ecosystems, with consequences for community composition and ecosystem functioning. Although studies of how changes in N availability affect biodiversity and community composition are relatively common, much less remains known about the effects of N inputs on the coupled biogeochemical cycling of N and phosphorus (P), and still fewer data exist regarding how increased N inputs affect the internal cycling of these two elements in plants. Nutrient resorption is an important driver of plant nutrient economies and of the quality of litter plants produce. Accordingly, resorption patterns have marked ecological implications for plant population and community fitness, as well as for ecosystem nutrient cycling. In a semiarid grassland in northern China, we studied the effects of a wide range of N inputs on foliar nutrient resorption of two dominant grasses, Leymus chinensis and Stipa grandis. After 4 years of treatments, N and P availability in soil and N and P concentrations in green and senesced grass leaves increased with increasing rates of N addition. Foliar N and P resorption significantly decreased along the N addition gradient, implying a resorption-mediated, positive plant-soil feedback induced by N inputs. Furthermore, N : P resorption ratios were negatively correlated with the rates of N addition, indicating the sensitivity of plant N and P stoichiometry to N inputs. Taken together, the results demonstrate that N additions accelerate ecosystem uptake and turnover of both N and P in the temperate steppe and that N and P cycles are coupled in dynamic ways. The convergence of N and P resorption in response to N inputs emphasizes the importance of nutrient resorption as a pathway by which plants and ecosystems adjust in the face of increasing N availability.

  13. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells.

    PubMed

    Li, Ziqing; Li, Chaohong; Zhou, Yuhuan; Chen, Weishen; Luo, Guotian; Zhang, Ziji; Wang, Haixing; Zhang, Yangchun; Xu, Dongliang; Sheng, Puyi

    2016-03-01

    Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW264.7 cell-derived osteoclast-like cells (OCLs). AGE-modified BSA (50-400 μg/ml) or control BSA (100 μg/ml) was then added at the beginning of each stage. Results showed that the presence of AGEs at the cell fusion stage reduced pit numbers, resorption area, and CTSK expression. Moreover, expression of receptor activator of nuclear factor-κB (RANK) as well as the number of TRAP-positive cells, nuclei per OCL, actin rings, and podosomes also decreased. However, the presence of AGEs at the mature stage enlarged the resorption area markedly and increased pit numbers slightly. Intriguingly, only the number of nuclei per OCL and podosomes increased. These data indicate that AGEs biphasically modulate bone resorption activity of OCLs in a differentiation stage-dependent manner. AGEs at the cell fusion stage reduce bone resorption dramatically, mainly via suppression of RANK expression in osteoclast precursors, whereas AGEs at the mature stage enhance bone resorption slightly, most likely by increasing the number of podosomes in mature OCLs.

  14. Overexpression of cathepsin K accelerates the resorption cycle and osteoblast differentiation in vitro.

    PubMed

    Morko, Jukka; Kiviranta, Riku; Mulari, Mika T K; Ivaska, Kaisa K; Väänänen, H Kalervo; Vuorio, Eero; Laitala-Leinonen, Tiina

    2009-04-01

    Bone resorption is a multistep process including osteoclast attachment, cytoskeletal reorganization, formation of four distinct plasma membrane domains, and matrix demineralization and degradation followed by cell detachment. The present study describes the intracellular mechanisms by which overexpression of cathepsin K in osteoclasts results in enhanced bone resorption. Osteoclasts and bone marrow-derived osteoclast and osteoblast precursors were isolated from mice homozygous (UTU17(+/+)) and negative for the transgene locus. Cells cultured on bovine cortical bone slices were analyzed by fluorescence and confocal laser scanning microscopy, and bone resorption was studied by measurements of biochemical resorption markers, morphometry, and FESEM. Excessive cathepsin K protein and enzyme activity were microscopically observed in various intracellular vesicles and in the resorption lacunae of cathepsin K-overexpressing osteoclasts. The number of cathepsin K-containing vesicles in UTU17(+/+) osteoclasts was highly increased, and co-localization with markers for the biosynthetic and transcytotic pathways was observed throughout the cytoplasm. As a functional consequence of cathepsin K overexpression, biochemical resorption markers were increased in culture media of UTU17(+/+) osteoclasts. Detailed morphometrical analysis of the erosion in bone slices indicated that the increased biosynthesis of cathepsin K was sufficient to accelerate the osteoclastic bone resorption cycle. Cathepsin K overexpression also enhanced osteogenesis and induced the formation of exceptionally small, actively resorbing osteoclasts from their bone marrow precursors in vitro. The present study describes for the first time how enhancement in one phase of the osteoclastic resorption cycle also stimulates its other phases and further demonstrate that tight control and temporal coupling of mesenchymal and hematopoietic bone cells in this multistep process.

  15. Self-assembling bisphosphonates into nanofibers to enhance their inhibitory capacity on bone resorption

    NASA Astrophysics Data System (ADS)

    Tang, Anming; Qian, Yu; Liu, Shuang; Wang, Weijuan; Xu, Bing; Qin, An; Liang, Gaolin

    2016-05-01

    Osteoporosis (OP) is an important aging-related disease and the effective prevention/treatment of this disease remains challenging. Considering the acidic microenvironment of bone resorption lacunae, herein, we rationally designed two pamidronate (Pami)-derivative and alendronate (Alen)-derivative hydrogelators Pami-D and Alen-D which self-assemble into nanofibers to form supramolecular hydrogels under acidic conditions. Cell viability assay, osteoclastogenesis, osteoclastic gene expression, and in vitro bone resorption results indicated that both Pami-D and Alen-D have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs Pami-D and Alen-D could ``smartly'' self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently.Osteoporosis (OP) is an important aging-related disease and the effective prevention/treatment of this disease remains challenging. Considering the acidic microenvironment of bone resorption lacunae, herein, we rationally designed two pamidronate (Pami)-derivative and alendronate (Alen)-derivative hydrogelators Pami-D and Alen-D which self-assemble into nanofibers to form supramolecular hydrogels under acidic conditions. Cell viability assay, osteoclastogenesis, osteoclastic gene expression, and in vitro bone resorption results indicated that both Pami-D and Alen-D have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs Pami-D and Alen-D could ``smartly'' self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently. Electronic supplementary information (ESI) available: Experiment methods and details; syntheses and characterization of Pami-D and Alen-D; HPLC conditions; Fig. S1-S15, Schemes S1 and S2, Tables S1 and S2

  16. Prevention and management of external inflammatory resorption following trauma to teeth.

    PubMed

    Abbott, P V

    2016-03-01

    External inflammatory resorption is one of the potential consequences of trauma to the teeth. It occurs when there has been loss of cementum due to damage to the external surface of the tooth root during trauma, plus the root canal system has become infected with bacteria. It is characterized by the radiographic appearance of loss of tooth substance with a radiolucency in the adjacent periodontal ligament and bone. The loss of cementum allows the intracanal bacteria and/or their endotoxins to reach the periodontal ligament more readily and this can lead to the development of the inflammatory resorptive process. External inflammatory resorption can ultimately lead to loss of the tooth if it is not managed in a timely manner. There are some injuries that are very likely to develop this type of resorption and a preventive approach can be adopted by commencing root canal treatment immediately as part of the emergency management of such cases. In cases where the resorptive process is already established, root canal treatment can arrest the resorption and encourage hard tissue repair. The use of a corticosteroid-antibiotic intracanal medicament has been shown to be particularly useful in the prevention and management of external inflammatory resorption. Calcium hydroxide should not be used as an immediate medicament because of its inherent toxicity and irritant properties but it is valuable as a subsequent medicament to encourage hard tissue repair where required. This review outlines the external inflammatory resorptive process and the management strategies that can be employed to prevent it from occurring, and to treat it if already present. PMID:26923450

  17. Resorption of bone implants. The effect of in vivo incorporation of a diphosphonate and fluoride on resorption.

    PubMed

    Rosenquist, J B; Baylink, D J

    1978-02-01

    Weanling isogenously related rats were divided into one control group, one group given a fluoride supplement of 100 parts/10(6) of F- in the drinking water, and a third group given 0.5 mg per kg body weight of phosphorus as dichloromethylene diphosphanic acid (Cl2MDP). The rats were labeled with 1 muCi per g body weight of 3H proline and 40 muCi of 45Ca. Four weeks after labeling, the animals were sacrificed and one scapula was implanted subcutaneously in the back of an isogenously related rat of the same age. The other scapula was stored in a freezer pending analysis. After another 4 weeks the implants were recovered and the radioactivity of each isotope was compared with that of the initially stored scapulae. A 30-40% loss of activity was found, reflecting a considerable loss of bone. However, this loss was significantly lower (P less than 0.01) when Cl2MDP was given to the donor animals, whereas fluoride treatment did not affect the resorption.

  18. Wormhole Travel for Macrophages.

    PubMed

    Okabe, Yasutaka; Medzhitov, Ruslan

    2016-04-21

    Leukocyte recruitment is generally achieved by rapid migration of inflammatory cells out of circulation, through modified blood vessels, and into affected tissues. Now, Wang and Kubes show that macrophages can be rapidly recruited from body cavities to the liver, via a non-vascular route, where they help to coordinate tissue repair.

  19. An automatic early stage alveolar-bone-resorption evaluation method on digital dental panoramic radiographs

    NASA Astrophysics Data System (ADS)

    Zhang, Min; Katsumata, Akitoshi; Muramatsu, Chisako; Hara, Takeshi; Suzuki, Hiroki; Fujita, Hiroshi

    2014-03-01

    Periodontal disease is a kind of typical dental diseases, which affects many adults. The presence of alveolar bone resorption, which can be observed from dental panoramic radiographs, is one of the most important signs of the progression of periodontal disease. Automatically evaluating alveolar-bone resorption is of important clinic meaning in dental radiology. The purpose of this study was to propose a novel system for automated alveolar-bone-resorption evaluation from digital dental panoramic radiographs for the first time. The proposed system enables visualization and quantitative evaluation of alveolar bone resorption degree surrounding the teeth. It has the following procedures: (1) pre-processing for a test image; (2) detection of tooth root apices with Gabor filter and curve fitting for the root apex line; (3) detection of features related with alveolar bone by using image phase congruency map and template matching and curving fitting for the alveolar line; (4) detection of occlusion line with selected Gabor filter; (5) finally, evaluation of the quantitative alveolar-bone-resorption degree in the area surrounding teeth by simply computing the average ratio of the height of the alveolar bone and the height of the teeth. The proposed scheme was applied to 30 patient cases of digital panoramic radiographs, with alveolar bone resorption of different stages. Our initial trial on these test cases indicates that the quantitative evaluation results are correlated with the alveolar-boneresorption degree, although the performance still needs further improvement. Therefore it has potential clinical practicability.

  20. CBCT evaluation of multiple idiopathic internal resorptions in permanent molars: case report

    PubMed Central

    2014-01-01

    Background Internal inflammatory root resorption is a rare condition in permanent teeth, which requires the presence of necrotic and infected pulp tissue within the coronal portion of the root canal system as well as inflamed pulp tissue apical to the resorptive defect. The aetiology of internal root resorption is not completely understandable, trauma and chronic pulpitis are considered the main risk factors. Case presentation We report a rare case of the multiple idiopathic resorption in the permanent maxillary and mandibular molars in a healthy 33-year-old female patient. In addition to clinical examination the patient was imaged using conventional radiography techniques and cone beam computed tomography (CBCT).The patient had recurrent throbbing pain in her # 46. The radiographic examination including “panoramic radiography and CBCT” revealed that radiographic evidence of internal resorption in #37 #36 #35 #34 #33 #47 #46 #45 #44 #43 #16 #15 #14 #13 and also including in unerupted #17, #26, #27, #28 teeth. The definitive diagnosis was made with the histopathological examination of the extracted tooth. Conclusions Internal root resorption is a rare clinical process that should be examined using different radiographic modalities. CBCT seems to be useful in evaluation of the lesions with superior diagnostic performance. PMID:24739085

  1. The complexity of nectar: secretion and resorption dynamically regulate nectar features

    NASA Astrophysics Data System (ADS)

    Nepi, Massimo; Stpiczyńska, Małgorzata

    2008-03-01

    In this paper, we review the phenomenon of nectar resorption, focusing on its physiological and ecological meaning. Nectar resorption is a phenomenon that has long been known but was rarely reported until the1990s. It has more recently been demonstrated in several species by various direct and indirect methodologies. It has generally been demonstrated in senescent flowers as a phenomenon separate in time from, and independent of, nectar secretion. The significance of this type of resorption is generally recognized as a resource-recovery strategy, recycling at least some materials invested in nectar production. Nevertheless, nectar resorption can occur concomitantly with nectar secretion. Nectar production is therefore best considered as a unified process comprising nectar secretion and resorption. The modulation of these two opposite phases allows nectar concentration to be maintained in a range suitable for pollinators (nectar homeostasis). The mechanism of nectar resorption at the cell level has received little attention, and its molecular basis can only be hypothesized on the basis of recent studies concerning sugar sensing.

  2. Role of carbonic anhydrase in bone resorption induced by prostaglandin E2 in vitro

    NASA Technical Reports Server (NTRS)

    Hall, G. E.; Kenny, A. D.

    1985-01-01

    The possible role of carbonic anhydrase in bone resorption induced by prostaglandin E2 (PGE2) was studied using an in vitro neonatal mouse calvarial culture system. PGE2 (10 to the -6th M) was effective in stimulating resorption, as assessed by calcium release into culture media. This enhanced resorption was accompanied by significant increases in calvarial carbonic anhydrase activity over control values at 48 and 96 h. At 48 h, bones treated with PGE2 had 20 percent more carbonic anhydrase activity than controls. By 96 h, treated bones contained 79 percent more carbonic anhydrase activity than controls. PGE2-induced bone resorption was inhibited by the carbonic anhydrase inhibitor acetazolamide in a dose-dependent fashion from 10 to the -5th to 10 to the -4th M with 77 percent inhibition observed at 10 to the -4th M. The acetazolamide analogue CL 13,850 (N-t-butylacetazolamide), which does not inhibit carbonic anhydrase, failed to inhibit PGE2-induced resorption. These results are consistent with the hypothesis that carbonic anhydrase is a necessary component of the osteoclastic bone resorptive mechanism.

  3. In vitro degradation and in vivo resorption of dicalcium phosphate cement based grafts.

    PubMed

    Sheikh, Zeeshan; Zhang, Yu Ling; Grover, Liam; Merle, Géraldine E; Tamimi, Faleh; Barralet, Jake

    2015-10-01

    There are two types of DCP: dihydrated (brushite) and anhydrous (monetite). After implantation, brushite converts to hydroxyapatite (HA) which resorbs very slowly. This conversion is not observed after implantation of monetite cements and result in a greater of resorption. The precise mechanisms of resorption and degradation however of these ceramics remain uncertain. This study was designed to investigate the effect of: porosity, surface area and hydration on in vitro degradation and in vivo resorption of DCP. Brushite and two types of monetite cement based grafts (produced by wet and dry thermal conversion) were aged in phosphate buffered saline (PBS) and bovine serum solutions in vitro and were implanted subcutaneously in rats. Here we show that for high relative porosity grafts (50-65%), solubility and surface area does not play a significant role towards in vitro mass loss with disintegration and fragmentation being the main factors dictating mass loss. For grafts having lower relative porosity (35-45%), solubility plays a more crucial role in mass loss during in vitro ageing and in vivo resorption. Also, serum inhibited dissolution and the formation of HA in brushite cements. However, when aged in PBS, brushite undergoes phase conversion to a mixture of octacalcium phosphate (OCP) and HA. This phase conversion was not observed for monetite upon ageing (in both serum and PBS) or in subcutaneous implantation. This study provides greater understanding of the degradation and resorption process of DCP based grafts, allowing us to prepare bone replacement materials with more predictable resorption profiles.

  4. Leptin regulation of bone resorption by the sympathetic nervous system and CART.

    PubMed

    Elefteriou, Florent; Ahn, Jong Deok; Takeda, Shu; Starbuck, Michael; Yang, Xiangli; Liu, Xiuyun; Kondo, Hisataka; Richards, William G; Bannon, Tony W; Noda, Masaki; Clement, Karine; Vaisse, Christian; Karsenty, Gerard

    2005-03-24

    Bone remodelling, the mechanism by which vertebrates regulate bone mass, comprises two phases, namely resorption by osteoclasts and formation by osteoblasts; osteoblasts are multifunctional cells also controlling osteoclast differentiation. Sympathetic signalling via beta2-adrenergic receptors (Adrb2) present on osteoblasts controls bone formation downstream of leptin. Here we show, by analysing Adrb2-deficient mice, that the sympathetic nervous system favours bone resorption by increasing expression in osteoblast progenitor cells of the osteoclast differentiation factor Rankl. This sympathetic function requires phosphorylation (by protein kinase A) of ATF4, a cell-specific CREB-related transcription factor essential for osteoblast differentiation and function. That bone resorption cannot increase in gonadectomized Adrb2-deficient mice highlights the biological importance of this regulation, but also contrasts sharply with the increase in bone resorption characterizing another hypogonadic mouse with low sympathetic tone, the ob/ob mouse. This discrepancy is explained, in part, by the fact that CART ('cocaine amphetamine regulated transcript'), a neuropeptide whose expression is controlled by leptin and nearly abolished in ob/ob mice, inhibits bone resorption by modulating Rankl expression. Our study establishes that leptin-regulated neural pathways control both aspects of bone remodelling, and demonstrates that integrity of sympathetic signalling is necessary for the increase in bone resorption caused by gonadal failure. PMID:15724149

  5. In vitro bone resorption is dependent on physiological concentrations of zinc.

    PubMed

    Chen, D; Waite, L C; Pierce, W M

    1998-01-01

    The addition of physiological concentrations of zinc (25-200 (microg/dL) to Dulbecco's Modified Eagle's Medium containing tibiae from 19-d chick embryos resulted in a concentration-dependent increase in tibial content of tartrate-resistant acid phosphatase (TRAP) and an increase in bone resorption, as measured by tibial calcium release. This increase in bone resorption was additive to the resorptive effect resulting from the addition of 10(-9)-10(-7) M parathyroid hormone (PTH), but was not additive to similar effects produced by the addition of 10(-9)-10(-7) M prostaglandin E2 (PGE2). An inhibitor of prostaglandin synthesis, flurbiprofen (10[-6] M), did not influence the effect of zinc on bone resorption. However, the addition of 2,6-pyridinedicarboxylic acid (10[-3] M, 2,6-PDCA), a chelator of zinc, did attenuate the effects of zinc, as did the addition of an inhibitor of DNA replication (hydroxyurea, 10[-3] M). Hydroxyurea also attenuated the bone resorptive response to PGE2, but had no influence on the effects of PTH. These results indicate that physiological concentrations of zinc alter bone resorptive rates in vitro by a mechanism that is dependent on DNA replication.

  6. Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer.

    PubMed

    Taube, T; Elomaa, I; Blomqvist, C; Beneton, M N; Kanis, J A

    1994-01-01

    We studied bone biopsies from 65 normocalcaemic women with breast cancer and predominantly osteolytic bone metastases in order to examine the pathophysiology of bone destruction in metastatic bone disease. Quantitative histomorphometric measurements were made at sites of tumour involvement, at sites adjacent to tumour tissue and at sites distant from tumour tissue. There were no significant differences in bone volume or in indices of bone resorption or formation between biopsies taken from sites distant from tumour and the controls. Bone resorption, as judged by eroded surface, increased progressively from bone distant from tumour to tumour-laden bone. The number of osteoclasts was significantly increased in bone immediately adjacent to tumour and within metastases. There was no decrease in the ratio of osteoclast to eroded surface in breast cancer compared to controls suggesting that increased resorption in breast cancer was mainly osteoclast mediated and locally activated by the tumour. Two thirds of the biopsies taken from tumour involved regions showed osteosclerosis with woven bone formation. The volume of the pre-existing lamellar trabecular bone was lower than normal in 75% of these biopsies, suggesting that bone resorption must have been increased before the onset of woven bone formation. Since all patients were receiving hormonal treatment or chemotherapy, it is likely that osteosclerosis at sites of previous resorption mainly resulted from the basic cancer treatment as a sign of response to treatment. Osteoclastic bone resorption was, however, not completely inhibited by the active cancer treatment.

  7. Bone resorption in incompletely impacted mandibular third molars and acute pericoronitis.

    PubMed

    Yamaoka, Minoru; Ono, Yusuke; Takahashi, Masahiro; Doto, Ryosuke; Yasuda, Kouichi; Uematsu, Takashi; Furusawa, Kiyofumi

    2009-01-01

    Acute pericoronitis (AP) arises frequently in incompletely impacted mandibular third molars, but it remains unknown whether bone resorption in aging is associated with acute inflammation of the third molar. We conducted an experiment to compare the ratio of bone resorption to root length in the distal surface of the second molar (A), the proximal surface (B), and distal surface (C) in mesio-angular, incompletely impacted third molars in 27 young and 58 older adults with AP and 77 young and 79 older adults without a history of AP. Bone resorption in A, B, and C in older adults with AP demonstrated a significantly higher ratio when compared to those without AP, whereas there was no difference between those with and without AP in young adults except for B in women. However, there were no differences between bone resorption in B with AP in young and older women, and between bone resorption in C with AP in young and older adults. These indicate that AP and bone resorption are associated with incompletely impacted mandibular third molars in older adults.

  8. Cone beam computed tomography study of apical root resorption induced by Herbst appliance

    PubMed Central

    SCHWARTZ, João Paulo; RAVELI, Taísa Boamorte; ALMEIDA, Kélei Cristina de Mathias; SCHWARTZ-FILHO, Humberto Osvaldo; RAVELI, Dirceu Barnabé

    2015-01-01

    Objective This study evaluated the frequency of root resorption during the orthodontic treatment with Herbst appliance by Cone Beam Computed Tomography (CBCT). Material and Methods The sample comprised 23 patients (11 men, 12 women; mean ages 15.76±1.75 years) with Class II division 1 malocclusion, treated with Herbst appliance. CBCT was obtained before treatment (T0) and after Herbst treatment (T1). All the dental roots, except third molars, were evaluated, and apical root resorption was determined using the axial guided navigation method. Paired t-tests and Wilcoxon T Test were used to compare the dependent samples in parametric and nonparametric cases, respectively. Chi-Square Test with Yates’ correction was used to evaluate the relationship between apical root resorption and gender. Results were considered at a significance level of 5%. Results Apical resorption was detected by CBCT in 57.96% of 980 roots that underwent Herbst appliance treatment. All patients had minimal resorption and there was no statistical significance between the genders. Conclusion CBCT three-dimensional evaluation showed association between Herbst appliance and minimal apical root resorption, mostly in the anchoring teeth, without clinical significance. PMID:26537718

  9. Resorption Rate Tunable Bioceramic: Si, Zn-Modified Tricalcium Phosphate

    SciTech Connect

    Wei, Xiang

    2006-01-01

    This dissertation is organized in an alternate format. Several manuscripts which have already been published or are to be submitted for publication have been included as separate chapters. Chapter 1 is a general introduction which describes the dissertation organization and introduces the human bone and ceramic materials as bone substitute. Chapter 2 is the background and literature review on dissolution behavior of calcium phosphate, and discussion of motivation for this research. Chapter 3 is a manuscript entitled ''Si,Zn-modified tricalcium phosphate: a phase composition and crystal structure study'', which was published in ''Key Engineering Materials'' [1]. Chapter 4 gives more crystal structure details by neutron powder diffraction, which identifies the position for Si and Zn substitution and explains the stabilization mechanism of the structure. A manuscript entitled ''Crystal structure analysis of Si, Zn-modified Tricalcium phosphate by Neutron Powder Diffraction'' will be submitted to Biomaterials [2]. Chapter 5 is a manuscript, entitled ''Dissolution behavior and cytotoxicity test of Si, Zn-modified tricalcium phosphate'', which is to be submitted to Biomaterials [3]. This paper discusses the additives effect on the dissolution behavior of TCP, and cytotoxicity test result is also included. Chapter 6 is the study of hydrolysis process of {alpha}-tricalcium phosphate in the simulated body fluid, and the phase development during drying process is discussed. A manuscript entitled ''Hydrolysis of {alpha}-tricalcium phosphate in simulated body fluid and phase transformation during drying process'' is to be submitted to Biomaterials [4]. Ozan Ugurlu is included as co-authors in these two papers due to his TEM contributions. Appendix A is the general introduction of the materials synthesis, crystal structure and preliminary dissolution result. A manuscript entitled ''Resorption rate tunable bioceramic: Si and Zn-modified tricalcium phosphate'' was published in

  10. Titanium particles and surface-bound LPS activate different pathways in IC-21 macrophages.

    PubMed

    Schwab, Luciana P; Xing, Zhiqing; Hasty, Karen A; Smith, Richard A

    2006-10-01

    It is still unknown if wear-debris particles themselves induce osteolysis or if they serve a functional role as receptors for ligands that incite an inflammatory response that ultimately leads to bone resorption. In this study, commercially pure titanium particles (cpTi) were subjected to a serial combination of different cleaning methods to remove Lipopolysaccharide (LPS) or were incubated in LPS solutions of known concentrations. Then, the response of the macrophage cell line IC-21 to the cleaned particles, LPS-bound Ti particles, and soluble LPS was examined. It was found that cleaned particles up to 1000 particles per cell did not stimulate macrophages to release Tumor necrosis factor-alpha (TNF-alpha) or Interleukin 6 (IL-6), but they significantly increased the release of Prostaglandin E(2) (PGE(2)) when the particle concentration was higher than 500 particles per cell. At one particle per cell, Ti particles bound with LPS stimulated the release of IL-6 and TNF-alpha by macrophages. The level of released cytokines was dependent on, and correlated with, the amount of LPS present on the particles. The macrophages were more sensitive to soluble LPS than to particle-bound LPS, and the simultaneous addition of cleaned Ti particles did not have additional effects on the effects of soluble LPS. This study shows evidence that, cpTi particles and LPS have distinct mechanisms of action on the IC-21 macrophages, but that both contribute to the development of an inflammatory response. PMID:16544307

  11. Transcriptional Regulation and Macrophage Differentiation.

    PubMed

    Hume, David A; Summers, Kim M; Rehli, Michael

    2016-06-01

    Monocytes and macrophages are professional phagocytes that occupy specific niches in every tissue of the body. Their survival, proliferation, and differentiation are controlled by signals from the macrophage colony-stimulating factor receptor (CSF-1R) and its two ligands, CSF-1 and interleukin-34. In this review, we address the developmental and transcriptional relationships between hematopoietic progenitor cells, blood monocytes, and tissue macrophages as well as the distinctions from dendritic cells. A huge repertoire of receptors allows monocytes, tissue-resident macrophages, or pathology-associated macrophages to adapt to specific microenvironments. These processes create a broad spectrum of macrophages with different functions and individual effector capacities. The production of large transcriptomic data sets in mouse, human, and other species provides new insights into the mechanisms that underlie macrophage functional plasticity. PMID:27337479

  12. Ultrasound stimulation attenuates resorption of tooth root induced by experimental force application.

    PubMed

    Inubushi, Toshihiro; Tanaka, Eiji; Rego, Emanuel B; Ohtani, Junji; Kawazoe, Aki; Tanne, Kazuo; Miyauchi, Mutsumi; Takata, Takashi

    2013-04-01

    Root resorption is an adverse outcome of orthodontic tooth movement. However, there have been no available approaches for the protection and repair of root resorption. The aim of this study was to evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on root resorption during experimental tooth movement and the effects of LIPUS in the RANKL/OPG mechanism in osteoblasts and cementoblasts in vitro. Twenty four Wistar strain male rats of 12-week-old were used in this study. The upper first molars were subjected to experimental movement in the mesial direction for 1-3weeks. Through the experimental periods, the right upper first maxillary molar was exposed to LIPUS (LIPUS group) every day for 1, 2 or 3weeks. The nature of root resorption was observed and then quantified by histomorphometric analysis. In the 2weeks period, significantly greater amount of tooth movement was observed in the LIPUS group (p<0.05). In addition, LIPUS group showed less root resorption lacunae and lower number of odontoclasts. In the period of 3weeks, LIPUS group presented significantly shorter length of root resorption lacunae and smaller amount of root resorption area (p<0.01). The number of odontoclasts and osteoclasts was also significantly lower in the LIPUS group (p<0.01 and p<0.05, respectively). However, no significant differences could be found regarding the amount of tooth movement. It is shown that LIPUS exposure significantly reduced the degree of root resorption during tooth movement without interrupting tooth movement. In vitro experiments showed that MC3T3-1 constitutively expressed higher levels of RANKL and RANTES mRNA comparing to OCCM-30. However, OPG mRNA expression was much higher in OCCM-30. LIPUS stimulation significantly increased the mRNA expression of RANKL in MC3T3-E1 at 4 (p<0.01) and 12h (p<0.05), although OPG mRNA expression was not affected by LIPUS. In contrast, the expression of RANKL and OPG mRNAs were both significantly increased by LIPUS in OCCM-30

  13. External apical root resorption in maxillary incisors in orthodontic patients: associated factors and radiographic evaluation

    PubMed Central

    Patanaporn, Virush; Janhom, Apirum; Korwanich, Narumanus

    2012-01-01

    Purpose This study was performed to evaluate the incidence and degree of external apical root resorption of maxillary incisors after orthodontic treatment and to evaluate particular associated factors related to external apical root resorption. Materials and Methods The records and maxillary incisor periapical radiographs of 181 patients were investigated. Crown and root lengths were measured and compared on the pre- and post-treatment periapical radiographs. Crown length was measured from the center of the incisal edge to the midpoint of the cemento-enamel junction (CEJ). Root length was measured from the CEJ midpoint to the root apex. A correction factor for the enlargement difference was used to calculate root resorption. Results The periapical radiographs of 564 teeth showed that the average root resorption was 1.39±1.27 (8.24±7.22%) and 1.69±1.14 mm (10.16±6.78%) for the maxillary central and lateral incisors, respectively. The results showed that the dilacerated or pointed roots, maxillary premolar extraction cases, and treatment duration were highly significant factors for root resorption (p<0.001). Allergic condition was a significant factor at p<0.01. Age at the start of treatment, large overjet, and history of facial trauma were also factors significantly associated with root resorption (p<0.05). There was no statistically significant difference in root resorption among the factors of gender, overbite, tongue-thrusting habit, types of malocclusion, and types of bracket. Conclusion These results suggested that orthodontic treatment should be carefully performed in pre-treatment extraction patients who have pointed or dilacerated roots and need long treatment duration. PMID:23071964

  14. Intracanal bisphosphonate does not inhibit replacement resorption associated with delayed replantation of monkey incisors.

    PubMed

    Thong, Yo Len; Messer, Harold H; Zain, Rosnah Binti; Saw, Lip Hean; Yoong, Lai Thong

    2009-08-01

    Progressive replacement resorption following delayed replantation of avulsed teeth has proved to be an intractable clinical problem. A wide variety of therapeutic approaches have failed to result in the predictable arrest of resorption, with a good long-term prognosis for tooth survival. Bisphosphonates are used in the medical management of a range of bone disorders and topically applied bisphosphonate has been reported to inhibit root resorption in dogs. This study evaluated the effectiveness of a bisphosphonate (etidronate disodium) as an intracanal medicament in the root canals of avulsed monkey teeth, placed before replantation after 1 h of extraoral dry storage. Incisors of six Macaca fascicularis monkeys were extracted and stored dry for 1 h. Teeth were then replanted after canal contamination with dental plaque (negative control) or after root canal debridement and placement of etidronate sealed in the canal space. A positive control of calcium hydroxide placed 8-9 days after replantation was also included. All monkeys were sacrificed 8 weeks later and block sections were prepared for histomorphometric assessment of root resorption and periodontal ligament status. Untreated teeth showed the greatest extent of root resorption (46% of the root surface), which was predominantly inflammatory in nature. Calcium hydroxide treated teeth showed the lowest overall level of resorption (<30% of the root surface), while the bisphosphonate-treated group was intermediate (39%). Ankylosis, defined as the extent of the root surface demonstrating direct bony union to both intact and resorbed root surface, was the lowest in the untreated control group (15% of the root surface), intermediate in the calcium hydroxide group (27%) and the highest in the bisphosphonate group (41%). Bony attachment to the tooth root was divided approximately equally between attachment to intact cementum and to previously resorbed dentin. Overall, bisphosphonate resulted in a worse outcome than

  15. Macrophage polarization following chitosan implantation.

    PubMed

    Vasconcelos, Daniela P; Fonseca, Ana C; Costa, Madalena; Amaral, Isabel F; Barbosa, Mário A; Águas, Artur P; Barbosa, Judite N

    2013-12-01

    Macrophages are a key cell in the host response to implants and can be polarized into different phenotypes capable of inducing both detrimental and beneficial outcomes in tissue repair and remodeling, being important in tissue engineering and regenerative medicine. The objective of this study was to evaluate the macrophage response to 3D porous chitosan (Ch) scaffolds with different degrees of acetylation (DA, 5% and 15%). The M1/M2 phenotypic polarization profile of macrophages was investigated in vivo using a rodent air-pouch model. Our results show that the DA affects the macrophage response. Ch scaffolds with DA 5% induced the adhesion of lower numbers of inflammatory cells, being the M2 the predominant phenotypic profile among the adherent macrophages. In the inflammatory exudates F4/80(+)/CD206(+) cells (M2 macrophages) appeared in higher numbers then F4/80(+)/CCR7(+) cells (M1 macrophages), in addition, lower levels of pro-inflammatory cytokines together with higher levels of anti-inflammatory cytokines were found. Ch scaffolds with DA 15% showed opposite results, since M1 were the predominant macrophages both adherent to the scaffold and in the exudates, together with high levels of pro-inflammatory cytokines. In conclusion, Ch scaffolds with DA 5% induced a benign M2 anti-inflammatory macrophage response, whereas Ch scaffolds with DA 15% caused a macrophage M1 pro-inflammatory response.

  16. Imaging macrophages with nanoparticles

    NASA Astrophysics Data System (ADS)

    Weissleder, Ralph; Nahrendorf, Matthias; Pittet, Mikael J.

    2014-02-01

    Nanomaterials have much to offer, not only in deciphering innate immune cell biology and tracking cells, but also in advancing personalized clinical care by providing diagnostic and prognostic information, quantifying treatment efficacy and designing better therapeutics. This Review presents different types of nanomaterial, their biological properties and their applications for imaging macrophages in human diseases, including cancer, atherosclerosis, myocardial infarction, aortic aneurysm, diabetes and other conditions. We anticipate that future needs will include the development of nanomaterials that are specific for immune cell subsets and can be used as imaging surrogates for nanotherapeutics. New in vivo imaging clinical tools for noninvasive macrophage quantification are thus ultimately expected to become relevant to predicting patients' clinical outcome, defining treatment options and monitoring responses to therapy.

  17. Early hematopoiesis and macrophage development.

    PubMed

    McGrath, Kathleen E; Frame, Jenna M; Palis, James

    2015-12-01

    The paradigm that all blood cells are derived from hematopoietic stem cells (HSCs) has been challenged by two findings. First, there are tissue-resident hematopoietic cells, including subsets of macrophages that are not replenished by adult HSCs, but instead are maintained by self-renewal of fetal-derived cells. Second, during embryogenesis, there is a conserved program of HSC-independent hematopoiesis that precedes HSC function and is required for embryonic survival. The presence of waves of HSC-independent hematopoiesis as well as fetal HSCs raises questions about the origin of fetal-derived adult tissue-resident macrophages. In the murine embryo, historical examination of embryonic macrophage and monocyte populations combined with recent reports utilizing genetic lineage-tracing approaches has led to a model of macrophage ontogeny that can be integrated with existing models of hematopoietic ontogeny. The first wave of hematopoiesis contains primitive erythroid, megakaryocyte and macrophage progenitors that arise in the yolk sac, and these macrophage progenitors are the source of early macrophages throughout the embryo, including the liver. A second wave of multipotential erythro-myeloid progenitors (EMPs) also arises in the yolk sac. EMPs colonize the fetal liver, initiating myelopoiesis and forming macrophages. Lineage tracing indicates that this second wave of macrophages are distributed in most fetal tissues, although not appreciably in the brain. Thus, fetal-derived adult tissue-resident macrophages, other than microglia, appear to predominately derive from EMPs. While HSCs emerge at midgestation and colonize the fetal liver, the relative contribution of fetal HSCs to tissue macrophages at later stages of development is unclear. The inclusion of macrophage potential in multiple waves of hematopoiesis is consistent with reports of their functional roles throughout development in innate immunity, phagocytosis, and tissue morphogenesis and remodeling

  18. Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory.

    PubMed

    Iwanowycz, Stephen; Wang, Junfeng; Altomare, Diego; Hui, Yvonne; Fan, Daping

    2016-05-27

    Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFNγ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFNγ- and IL4-responsive genes through inhibiting NFκB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies.

  19. Epigenomics of macrophages.

    PubMed

    Gosselin, David; Glass, Christopher K

    2014-11-01

    Macrophages play essential roles in tissue homeostasis, pathogen elimination, and tissue repair. A defining characteristic of these cells is their ability to efficiently adapt to a variety of abruptly changing and complex environments. This ability is intrinsically linked to a capacity to quickly alter their transcriptome, and this is tightly associated with the epigenomic organization of these cells and, in particular, their enhancer repertoire. Indeed, enhancers are genomic sites that serve as platforms for the integration of signaling pathways with the mechanisms that regulate mRNA transcription. Notably, transcription is pervasive at active enhancers and enhancer RNAs (eRNAs) are tightly coupled to regulated transcription of protein-coding genes. Furthermore, given that each cell type possesses a defining enhancer repertoire, studies on enhancers provide a powerful method to study how specialization of functions among the diverse macrophage subtypes may arise. Here, we review recent studies providing insights into the distinct mechanisms that contribute to the establishment of enhancers and their role in the regulation of transcription in macrophages.

  20. Epigenomics of macrophages

    PubMed Central

    Gosselin, David; Glass, Christopher K

    2014-01-01

    Summary Macrophages play essential roles in tissue homeostasis, pathogen elimination, and tissue repair. A defining characteristic of these cells is their ability to efficiently adapt to a variety of abruptly changing and complex environments. This ability is intrinsically linked to a capacity to quickly alter their transcriptome, and this is tightly associated with the epigenomic organization of these cells and, in particular, their enhancer repertoire. Indeed, enhancers are genomic sites that serve as platforms for the integration of signaling pathways with the mechanisms that regulate mRNA transcription. Notably, transcription is pervasive at active enhancers and enhancer RNAs (eRNAs) are tightly coupled to regulated transcription of protein-coding genes. Furthermore, given that each cell type possesses a defining enhancer repertoire, studies on enhancers provide a powerful method to study how specialization of functions among the diverse macrophage subtypes may arise. Here, we review recent studies providing insights into the distinct mechanisms that contribute to the establishment of enhancers and their role in the regulation of transcription in macrophages. PMID:25319330

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

    PubMed Central

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

    2015-01-01

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

  2. The macrophages in rheumatic diseases

    PubMed Central

    Laria, Antonella; Lurati, Alfredomaria; Marrazza, Mariagrazia; Mazzocchi, Daniela; Re, Katia Angela; Scarpellini, Magda

    2016-01-01

    Macrophages belong to the innate immune system giving us protection against pathogens. However it is known that they are also involved in rheumatic diseases. Activated macrophages have two different phenotypes related to different stimuli: M1 (classically activated) and M2 (alternatively activated). M1 macrophages release high levels of pro-inflammatory cytokines, reactive nitrogen and oxygen intermediates killing microorganisms and tumor cells; while M2 macrophages are involved in resolution of inflammation through phagocytosis of apoptotic neutrophils, reduced production of pro-inflammatory cytokines, and increased synthesis of mediators important in tissue remodeling, angiogenesis, and wound repair. The role of macrophages in the different rheumatic diseases is different according to their M1/M2 macrophages phenotype. PMID:26929657

  3. Effect of fangchinoline on root resorption during rat orthodontic tooth movement

    PubMed Central

    Bao, Xingfu; Zhang, Yi; Machibya, Ferdinand; Zhang, Ying; Jiang, Huan; Yu, Dongsheng

    2012-01-01

    Objective To evaluate the short-term effect of fangchinoline, an antiinflammatory drug widely used in Asia, on root resorption that is associated with orthodontic tooth movement. Methods Twenty-four Wistar rats were randomly divided into 6 groups. Mesial forces of 0, 50, or 100 g were applied to the maxillary first molar of the rats in each group for 14 days by activating nickel-titanium closed-coil springs. One-half of the rats receiving each of these treatments also received injections of 200 µL fangchinoline every 2 days. Finally, movement of the maxillary first molars was measured using digitized radiographs. The molars were extracted and the surfaces of the root resorption craters were recorded using a scanning electron microscope. The distance the molars moved and resorptionarea ratio was measured, and results were analyzed using 2-way ANOVA tests. Results There were no statistical differences in the distances the first molars moved under 50 or 100 g force, regardless of treatment with fangchinoline. However, the resorption area ratios were significantly smaller in those rats that were treated with both tension and fangchinoline than in those rats treated by tension alone. Conclusions Fangchinoline reduced the resorption area ratio in rats and is therefore an important means of alleviating root resorption. PMID:23112944

  4. Diagnostic Accuracy of Cone-Beam Computed Tomography and Periapical Radiography in Internal Root Resorption

    PubMed Central

    Madani, Zahrasadat; Moudi, Ehsan; Bijani, Ali; Mahmoudi, Elham

    2016-01-01

    Introduction: The aim of this study was to compare the diagnostic value of cone-beam computed tomography (CBCT) and periapical (PA) radiography in detecting internal root resorption. Methods and Materials: Eighty single rooted human teeth with visible pulps in PA radiography were split mesiodistally along the coronal plane. Internal resorption like lesions were created in three areas (cervical, middle and apical) in labial wall of the canals in different diameters. PA radiography and CBCT images were taken from each tooth. Two observers examined the radiographs and CBCT images to evaluate the presence of resorption cavities. The data were statistically analyzed and degree of agreement was calculated using Cohen’s kappa (k) values. Results: The mean±SD of agreement coefficient of kappa between the two observers of the CBCT images was calculated to be 0.681±0.047. The coefficients for the direct, mesial and distal PA radiography were 0.405±0.059, 0.421±0.060 and 0.432±0.056, respectively (P=0.001). The differences in the diagnostic accuracy of resorption of different sizes were statistically significant (P<0.05); however, the PA radiography and CBCT, had no statistically significant differences in detection of internal resorption lesions in the cervical, middle and apical regions. Conclusion: Though, CBCT has a higher sensitivity, specificity, positive predictive value and negative predictive value in comparison with conventional radiography, this difference was not significant. PMID:26843878

  5. Resorption Protection. Anthocyanins Facilitate Nutrient Recovery in Autumn by Shielding Leaves from Potentially Damaging Light Levels

    PubMed Central

    Hoch, William A.; Singsaas, Eric L.; McCown, Brent H.

    2003-01-01

    The resorption protection hypothesis, which states that anthocyanins protect foliar nutrient resorption during senescence by shielding photosynthetic tissues from excess light, was tested using wild-type (WT) and anthocyanin-deficient mutants of three deciduous woody species, Cornus sericea, Vaccinium elliottii (Chapmn.), and Viburnum sargentii (Koehne). WT Betula papyrifera (Marsh) was included to compare the senescence performance of a species that does not produce anthocyanins in autumn. Plants were subjected to three environmental regimes during senescence: an outdoor treatment; a 5-d high-stress (high light and low temperature) treatment followed by transfer to a low-stress environment and a low-stress treatment that served as control. In the outdoor treatment, the appearance of anthocyanins in senescing leaves of WT plants was concomitant with the development of photo-inhibition in mutant plants of all three anthocyanin-producing species. In the high-stress environment, WT plants maintained higher photochemical efficiencies than mutants and were able to recover when transferred to the low-stress environment, whereas mutant leaves dropped while still green and displayed signs of irreversible photooxidative damage. Nitrogen resorption efficiencies and proficiencies of all mutants in both stressful treatments were significantly lower than the WT counterparts. B. papyrifera displayed photochemical efficiencies and nitrogen resorption performance comparable with the highest of the anthocyanin-producing species in all three senescing environments, indicating a photoprotective strategy divergent from the other species studied. These results strongly support the resorption protection hypothesis of anthocyanins in senescing leaves. PMID:14526111

  6. Modulating Bone Resorption and Bone Formation in Opposite Directions in the Treatment of Postmenopausal Osteoporosis.

    PubMed

    Appelman-Dijkstra, Natasha M; Papapoulos, Socrates E

    2015-07-01

    Bone remodeling, the fundamental process for bone renewal, is targeted by treatments of osteoporosis to correct the imbalance between bone resorption and bone formation and reduce the risk of fractures and associated clinical consequences. Currently available therapeutics affect bone resorption and bone formation in the same direction and either decrease (inhibitors of bone resorption) or increase (parathyroid hormone [PTH] peptides) bone remodeling. Studies of patients with rare bone diseases and genetically modified animal models demonstrated that bone resorption and bone formation may not necessarily be coupled, leading to identification of molecular targets in bone cells for the development of novel agents for the treatment of osteoporosis. Application of such agents to the treatment of women with low bone mass confirmed that bone resorption and bone formation can be modulated in different directions and so far two new classes of therapeutics for osteoporosis have been defined with distinct mechanisms of action. Such treatments, if combined with a favorable safety profile, will offer new therapeutic options and will improve the management of patients with osteoporosis.

  7. Conservative management of external root resorption after tooth reimplantation: a 3-year follow-up.

    PubMed

    Ionta, Franciny Querobim; de Oliveira, Gabriela Cristina; de Alencar, Catarina Ribeiro Barros; Gonçalves, Priscilla Santana Pinto; Alcalde, Murilo Priori; Minotti, Paloma Gagliardi; Machado, Maria Aparecida de Andrade Moreira; Rios, Daniela

    2016-01-01

    The aim of this case report is to describe the treatment of a 9-year-old patient who suffered external root resorption of the permanent maxillary left lateral incisor following reimplantation of the avulsed left central and lateral incisors. Sixteen days after reimplantation and splinting of the incisors in a hospital emergency department, the patient was brought to the pediatric department of a dental school for further treatment. Root canal access was created in the maxillary left lateral and central incisors, and calcium hydroxide paste was used as intracanal dressing. At the 5-month follow-up, a radiograph revealed extensive external root resorption, a communicating root canal, and a periodontal lesion affecting the left lateral incisor. Management of the root resorption included obturation of the apical third of the canal with gutta percha and the middle third with mineral trioxide aggregate (MTA). At the 3-year recall examination, the patient was asymptomatic, and no mobility or soft tissue alterations were observed clinically. There was no radiographic sign that resorption had progressed. Despite the success of treatment, observation is still required. The use of MTA may be considered an alternative treatment for external root resorption after tooth reimplantation. The technique may allow tooth preservation in children until skeletal growth and development are completed and implant treatment may be considered. PMID:27367632

  8. Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography.

    PubMed

    Lambers, F M; Stuker, F; Weigt, C; Kuhn, G; Koch, K; Schulte, F A; Ripoll, J; Rudin, M; Müller, R

    2013-02-01

    Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, p<0.01), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89-109% greater (p<0.05) for mice subjected to mechanical loading than control mice. Bone resorption was 5-8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice.

  9. Soil nitrogen drives community-level phosphorus resorption in a co-limited system: evidence from a northern hardwood forest

    NASA Astrophysics Data System (ADS)

    See, C. R.; Yanai, R. D.

    2013-12-01

    Fertilization studies in northeastern forests suggest that forest productivity may be co-limited by nitrogen and phosphorus. Foliar nutrient resorption is a crucial conservation mechanism for plants. Resorption controls litterfall nutrient concentration, and litterfall is the largest aboveground nutrient flux in this system. Previous studies have attempted to link the foliar resorption of P to soil P status with mixed results. We propose that in an N and P co-limited system, foliar resorption of P may be linked to N availability. Here we compare the foliar chemistry of six hardwood tree species to soil chemistry across 18 plots in 6 stands in Bartlett Experimental Forest, New Hampshire. Resorption efficiency was calculated by species as the percent difference between green and senesced leaves. We weighted the resorption efficiencies for dominant tree species in each plot by their litterfall mass to create a community-level estimate of resorption for each plot. Estimates of soil N content to 30 centimeters in the mineral soil were strongly correlated with community-level estimates of both P resorption efficiency (p=0.002) and proficiency (p=0.006). At the population level, this trend was observed in four of the six tree species sampled. Neither N nor P resorption was correlated with any of the soil P fractions we examined. If N availability drives biological P conservation, it would provide an important mechanism for the coupled cycling of N and P in co-limited systems.

  10. Macrophage Roles Following Myocardial Infarction

    PubMed Central

    Lambert, Jessica M.; Lopez, Elizabeth F.; Lindsey, Merry L.

    2010-01-01

    Following myocardial infarction (MI), circulating blood monocytes respond to chemotactic factors, migrate into the infarcted myocardium, and differentiate into macrophages. At the injury site, macrophages remove necrotic cardiac myocytes and apoptotic neutrophils; secrete cytokines, chemokines, and growth factors; and modulate phases of the angiogenic response. As such, the macrophage is a primary responder cell type that is involved in the regulation of post-MI wound healing at multiple levels. This review summarizes what is currently known about macrophage functions post-MI and borrows literature from other injury and inflammatory models to speculate on additional roles. Basic science and clinical avenues that remain to be explored are also discussed. PMID:18656272

  11. Bioelectric modulation of macrophage polarization

    NASA Astrophysics Data System (ADS)

    Li, Chunmei; Levin, Michael; Kaplan, David L.

    2016-02-01

    Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells’ resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine.

  12. Macrophages in homeostatic immune function.

    PubMed

    Jantsch, Jonathan; Binger, Katrina J; Müller, Dominik N; Titze, Jens

    2014-01-01

    Macrophages are not only involved in inflammatory and anti-infective processes, but also play an important role in maintaining tissue homeostasis. In this review, we summarize recent evidence investigating the role of macrophages in controlling angiogenesis, metabolism as well as salt and water balance. Particularly, we summarize the importance of macrophage tonicity enhancer binding protein (TonEBP, also termed nuclear factor of activated T-cells 5 [NFAT5]) expression in the regulation of salt and water homeostasis. Further understanding of homeostatic macrophage function may lead to new therapeutic approaches to treat ischemia, hypertension and metabolic disorders. PMID:24847274

  13. Macrophages in homeostatic immune function

    PubMed Central

    Jantsch, Jonathan; Binger, Katrina J.; Müller, Dominik N.; Titze, Jens

    2014-01-01

    Macrophages are not only involved in inflammatory and anti-infective processes, but also play an important role in maintaining tissue homeostasis. In this review, we summarize recent evidence investigating the role of macrophages in controlling angiogenesis, metabolism as well as salt and water balance. Particularly, we summarize the importance of macrophage tonicity enhancer binding protein (TonEBP, also termed nuclear factor of activated T-cells 5 [NFAT5]) expression in the regulation of salt and water homeostasis. Further understanding of homeostatic macrophage function may lead to new therapeutic approaches to treat ischemia, hypertension and metabolic disorders. PMID:24847274

  14. Nonsurgical management of a large periapical lesion associated with an immature tooth displaying external inflammatory resorption

    PubMed Central

    Fernandes, Marina; de Ataide, Ida

    2015-01-01

    Immature nonvital teeth can often be associated with periapical lesions. Presence of external inflammatory resorption can complicate the treatment plan. A 21-year-old female patient presented with a large periapical lesion in relation to teeth 11 and 12. Tooth 11 was an immature tooth undergoing external inflammatory resorption. Aspiration through the root canal was carried out to evacuate the purulent fluid in the periapical lesion. Triple antibiotic paste was then placed as an intracanal medicament for a period of 2 weeks, followed by calcium hydroxide therapy for a period of 2 months. Mineral trioxide aggregate was then placed as an apical barrier to a thickness of about 4 mm. Obturation of the remainder of the canal space was done after 48 h. Complete periapical healing was evident after 1 year and 6 months. Nonsurgical healing of a large periapical lesion associated with an immature tooth displaying external inflammatory resorption can be successfully achieved. PMID:26180425

  15. Plasma fluctuation in estradiol-17β and bone resorption markers around parturition in dairy cows.

    PubMed

    Devkota, Bhuminad; Takahashi, Masahiro; Sato, Saori; Sasaki, Kouya; Ueki, Atsushi; Osawa, Takeshi; Takahashi, Masahiro; Yamagishi, Norio

    2015-07-01

    Blood samples were obtained sequentially from 10 dairy cows around the time of parturition to assess plasma fluctuations in estradiol-17β (E2) levels in association with those of several bone resorption markers. Plasma E2 concentration increased sharply a few days prepartum and decreased quickly after parturition. In terms of bone resorption markers, the plasma level of tartrate-resistant acid phosphatase isoform 5b (TRAP5b) rose significantly, commencing 1 week prepartum, and was maintained at this level to a few days postpartum. The plasma concentration of carboxyterminal collagen cross-links of type-I collagen (CTx) increased significantly after parturition. These observations suggest that osteoclast-mediated bone resorption was activated after parturition when plasma E2 concentrations decreased.

  16. Bis-Enoxacin Blocks Rat Alveolar Bone Resorption from Experimental Periodontitis

    PubMed Central

    Lee, Ju-Youn; Bhattacharyya, Indraneel; Dolce, Calogero; Toro, Edgardo J.; Holliday, L. Shannon; Kesavalu, Lakshmyya

    2014-01-01

    Periodontal diseases are multifactorial, caused by polymicrobial subgingival pathogens, including Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Chronic periodontal infection results in inflammation, destruction of connective tissues, periodontal ligament, and alveolar bone resorption, and ultimately tooth loss. Enoxacin and a bisphosphonate derivative of enoxacin (bis-enoxacin) inhibit osteoclast formation and bone resorption and also contain antibiotic properties. Our study proposes that enoxacin and/or bis-enoxacin may be useful in reducing alveolar bone resorption and possibly bacterial colonization. Rats were infected with 109 cells of polymicrobial inoculum consisting of P. gingivalis, T. denticola, and T. forsythia, as an oral lavage every other week for twelve weeks. Daily subcutaneous injections of enoxacin (5 mg/kg/day), bis-enoxacin (5, 25 mg/kg/day), alendronate (1, 10 mg/kg/day), or doxycycline (5 mg/day) were administered after 6 weeks of polymicrobial infection. Periodontal disease parameters, including bacterial colonization/infection, immune response, inflammation, alveolar bone resorption, and systemic spread, were assessed post-euthanasia. All three periodontal pathogens colonized the rat oral cavity during polymicrobial infection. Polymicrobial infection induced an increase in total alveolar bone resorption, intrabony defects, and gingival inflammation. Treatment with bis-enoxacin significantly decreased alveolar bone resorption more effectively than either alendronate or doxycycline. Histologic examination revealed that treatment with bis-enoxacin and enoxacin reduced gingival inflammation and decreased apical migration of junctional epithelium. These data support the hypothesis that bis-enoxacin and enoxacin may be useful for the treatment of periodontal disease. PMID:24638087

  17. The Effect of Ovariectomy and Orchiectomy on Orthodontic Tooth Movement and Root Resorption in Wistar Rats

    PubMed Central

    Seifi, Massoud; Ezzati, Baharak; Saedi, Sara; Hedayati, Mehdi

    2015-01-01

    Statement of the Problem Root resorption (RR) after orthodontic tooth movement (OTM) is known as a multifactorial complication of orthodontic treatments. Hormonal deficiencies and their effect on bone turnover are reported to have influences on the rate of tooth movement and root resorption. Purpose This study was designed to evaluate the effect of female and male steroid sex hormones on tooth movement and root resorption. Materials and Method Orthodontic appliances were placed on the right maxillary first molars of 10 ovariectomized female and 10 orchiectomized male Wistar rats as experimental groups and 10 female and 10 male healthy Wistar rats as control groups. NiTi closed-coil springs (9mm, Medium, 011"×.030", Ortho Technology®; Tampa, Florida) were placed between the right incisors and the first right maxillary molars to induce tipping movement in the first molars with the application of a 60g force. After 21 days, the rats were sacrificed and tooth movement was measured by using a digital caliper (Guanglu, China). Orthodontic induced root resorption (OIRR) was assessed by histomorphometric analysis after hematoxylin and eosin staining of sections of the mesial root. Results The rate of tooth movement was significantly higher in all female rats, with the root resorption being lower in the experimental group. The rate of tooth movement in experimental male rats was significantly higher than the control group (p= 0.001) and the rate of root resorption was significantly lower in the experimental group (p= 0.001). Conclusion It seems that alterations in plasma levels of estrogen, progesterone, and testosterone hormones can influence the rate of OTM and RR. The acceleration in tooth movement increased OTM and decreased RR. PMID:26636117

  18. Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption.

    PubMed

    Razi, Hajar; Birkhold, Annette I; Weinkamer, Richard; Duda, Georg N; Willie, Bettina M; Checa, Sara

    2015-10-01

    Physical activity is essential to maintain skeletal mass and structure, but its effect seems to diminish with age. To test the hypothesis that bone becomes less sensitive to mechanical strain with age, we used a combined in vivo/in silico approach. We investigated how maturation and aging influence the mechanical regulation of bone formation and resorption to 2 weeks of noninvasive in vivo controlled loading in mice. Using 3D in vivo morphometrical assessment of longitudinal microcomputed tomography images, we quantified sites in the mouse tibia where bone was deposited or resorbed in response to controlled in vivo loading. We compared the (re)modeling events (formation/resorption/quiescent) to the mechanical strains induced at these sites (predicted using finite element analysis). Mice of all age groups (young, adult, and elderly) responded to loading with increased formation and decreased resorption, preferentially at high strains. Low strains were associated with no anabolic response in adult and elderly mice, whereas young animals showed a strong response. Adult animals showed a clear separation between strain ranges where formation and resorption occurred but without an intermediate quiescent "lazy zone". This strain threshold disappeared in elderly mice, as mechanically induced (re)modeling became dysregulated, apparent in an inability to inhibit resorption or initiate formation. Contrary to what is generally believed until now, aging does not shift the mechanical threshold required to initiate formation or resorption, but rather blurs its specificity. These data suggest that pharmaceutical strategies augmenting physical exercise should consider this dysfunction in the mechanical regulation of bone (re)modeling to more effectively combat age-related bone loss.

  19. A radiographic comparison of apical root resorption after orthodontic treatment with the edgewise and Speed appliances.

    PubMed

    Blake, M; Woodside, D G; Pharoah, M J

    1995-07-01

    Apical root resorption is a serious iatrogenic problem sometimes associated with orthodontic treatment. The Speed appliance (Strite Industries, Ltd., Ontario, Canada) provides a continuous rotatory and torque action through its spring clip mechanism, in contrast with the edgewise appliance that may provide an interrupted force. The effect of continuous action on root resorption compared with the interrupted action of the edgewise system has not been investigated previously. The purpose of the present investigation is to test the null hypothesis that there is no difference in the apical root resorption seen after orthodontic treatment with the edgewise straight wire and the Speed appliance systems. Pretreatment and posttreatment periapical radiographs of 63 patients, (30 treated with the Speed 0.018 bracket and 33 with the 0.018 edgewise bracket) were studied. The long cone paralleling technique was used for all the radiographs. Any image distortion between the pretreatment and posttreatment radiograph was calculated and compensated for by using the crown length measurements, on the assumption that the crown length remains unaltered during the treatment period. Quantitative measurements of crown and root lengths for the maxillary and the mandibular central and lateral incisors were compared. Means and standard deviations for the percentage root resorption per tooth group were calculated. A three-factor analysis for variance (ANOVA test) was performed to determine whether there was an appliance, treatment, or gender effect on the amount of root resorption seen after treatment. No statistically significant difference in root resorption between the two appliance systems was found.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Bis-enoxacin blocks rat alveolar bone resorption from experimental periodontitis.

    PubMed

    Rivera, Mercedes F; Chukkapalli, Sasanka S; Velsko, Irina M; Lee, Ju-Youn; Bhattacharyya, Indraneel; Dolce, Calogero; Toro, Edgardo J; Holliday, L Shannon; Kesavalu, Lakshmyya

    2014-01-01

    Periodontal diseases are multifactorial, caused by polymicrobial subgingival pathogens, including Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Chronic periodontal infection results in inflammation, destruction of connective tissues, periodontal ligament, and alveolar bone resorption, and ultimately tooth loss. Enoxacin and a bisphosphonate derivative of enoxacin (bis-enoxacin) inhibit osteoclast formation and bone resorption and also contain antibiotic properties. Our study proposes that enoxacin and/or bis-enoxacin may be useful in reducing alveolar bone resorption and possibly bacterial colonization. Rats were infected with 10(9) cells of polymicrobial inoculum consisting of P. gingivalis, T. denticola, and T. forsythia, as an oral lavage every other week for twelve weeks. Daily subcutaneous injections of enoxacin (5 mg/kg/day), bis-enoxacin (5, 25 mg/kg/day), alendronate (1, 10 mg/kg/day), or doxycycline (5 mg/day) were administered after 6 weeks of polymicrobial infection. Periodontal disease parameters, including bacterial colonization/infection, immune response, inflammation, alveolar bone resorption, and systemic spread, were assessed post-euthanasia. All three periodontal pathogens colonized the rat oral cavity during polymicrobial infection. Polymicrobial infection induced an increase in total alveolar bone resorption, intrabony defects, and gingival inflammation. Treatment with bis-enoxacin significantly decreased alveolar bone resorption more effectively than either alendronate or doxycycline. Histologic examination revealed that treatment with bis-enoxacin and enoxacin reduced gingival inflammation and decreased apical migration of junctional epithelium. These data support the hypothesis that bis-enoxacin and enoxacin may be useful for the treatment of periodontal disease.

  1. Potential and realized nutrient resorption in serpentine and non-serpentine chaparral shrubs and trees.

    PubMed

    Drenovsky, Rebecca E; Koehler, Catherine E; Skelly, Kathryn; Richards, James H

    2013-01-01

    Low-nutrient adapted species have numerous mechanisms that aid in nutrient conservation. Hypothetically, species adapted to nutrient-poor soils should have tighter internal nutrient recycling, as evidenced by greater resorption. However, literature results are mixed. We suggest methodological factors may limit our understanding of this process. We hypothesized that plants adapted to serpentine soils would be more proficient in resorbing N and P than plants adapted to non-serpentine soils, although there would be differences among functional groups within each soil type. For six growing seasons, we sampled senescent leaf tissue from the dominant and co-dominant shrubs and trees found in serpentine and non-serpentine chaparral communities in the California Coast Range. Our study also explicitly included congener pairs found on both soil types. Most species were highly N proficient, but species adapted to serpentine soils were more P proficient. Surprisingly, two of the three potential N-fixing species were also highly N proficient. Evergreen Quercus congeners were more N proficient than their deciduous congener pairs, although there was no difference in P resorption proficiency. Overall, large inter-annual variation was observed among most species sampled, but at least in some years, maximum potential resorption likely was reached. However, climate (temperature and precipitation) was not strongly correlated with either N or P resorption proficiency. Our data suggest that controlling for phylogeny can aid in interpretation of resorption patterns. More importantly, our study clearly shows that resorption patterns can only be discerned through long-term datasets, of which few exist in the literature.

  2. Dissolved water distribution in vesicular magmatic glass records both decompressive bubble growth and quench resorption

    NASA Astrophysics Data System (ADS)

    McIntosh, I. M.; Llewellin, E.; Humphreys, M.; Nichols, A. R.; Burgisser, A.; Schipper, C.

    2013-12-01

    Water distribution in magma varies over the lifetime of an eruption due to a variety of processes, including decompressive degassing of the melt, cooling during the quench from melt to glass, and post-emplacement hydration under ambient conditions. Correct interpretation of water distributions in erupted pyroclasts can therefore offer crucial insights into the dynamics of eruption mechanisms and emplacement histories. Volcanic eruptions are driven by the nucleation and growth of bubbles in magma. Bubbles grow as volatile species in the melt, of which water is volumetrically the most important, diffuse down a concentration gradient towards and across the bubble wall. On cooling, the melt quenches to glass, preserving the spatial distribution of water concentration around the bubbles (now vesicles). We use Backscatter Scanning Electron Microscopy (BSEM), Secondary Ion Mass Spectrometry (SIMS) and Fourier Transform Infra-Red spectroscopy (FTIR) to measure the spatial distribution of water around vesicles in experimentally-vesiculated samples. We find that, contrary to expectation, the total water concentration increases (by up to 2 wt.%) in the ~30 microns closest to the vesicle wall. Our samples record significant resorption of water back into the melt around bubbles during the quench process, a process which represents ';regassing' of the magma. We propose that the observed total water resorption profiles result from the increase in the equilibrium solubility of water as temperature decreases during the quench to glass, and that this resorption locally overprints the pre-existing concentration total water profile resulting from bubble growth during decompression. This resorption occurs over the very short timescales of rapid experimental quench (3-10 seconds) resulting in strongly disequilibrium water speciation. Water re-enters the melt as molecular water leading to enrichment in molecular water around vesicles, while the distribution of hydroxyl groups remains

  3. Influence of radiation resorption on criteria of the existence of local thermodynamic equilibrium

    SciTech Connect

    Denisova, N.V.; Preobrazhenskii, N.G.; Sevast'yanenko, V.G.

    1986-12-01

    The emission of radiation from a plasma volume upsets the Boltzmann equilibrium. A number of authors have proposed criteria for approximate testing of the existence of local thermodynamic equilibrium on the basis of collision and radiation processes. However, those criteria give excessive values, because they do not take into account radiation resorption, which can moderate the test conditions. The present article is concerned with the influence of radiation resorption on the criterion of the existence of local thermodynamic equilibrium in a low-temperature plasma. The domain of existence of local thermodynamic equilibrium (in the sense of Saha-Boltzmann equilibrium) is calculated for electric arcs.

  4. Role of macrophages in the biological reaction to wear debris from joint replacements.

    PubMed

    Nich, Christophe; Goodman, Stuart B

    2014-01-01

    Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene particles are heavily involved in the stimulation of local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone resorption (osteolysis), and, eventually, implant loosening. As sentinels of the innate immune system, cells of the monocyte/macrophage lineage initiate the inflammatory cascade that leads to osteolysis. The biological processes involved are complex, based on the unique properties of the monocytes/macrophages, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The interaction with wear debris triggers the release of pro-inflammatory factors, such as TNF-α, IL-1, and others, pro-osteoclastic factors such as RANKL, and chemokines, such as MCP-1 and MIP-1, all being crucial to the recruitment, migration, differentiation, and ultimately activation of bone resorbing osteoclasts. In parallel, other distinct macrophage populations inhibit inflammation and mitigate its consequences on the bone-implant interface. Here, the role of the monocyte/macrophage cell lineage in the initiation and maintenance of the host inflammatory response to wear debris and subsequent periprosthetic osteolysis is presented. PMID:25747029

  5. Adipose tissue macrophages: amicus adipem?

    PubMed Central

    Odegaard, Justin I.; Ganeshan, Kirthana; Chawla, Ajay

    2014-01-01

    Chronic overnutrition drives complex adaptations within both professional metabolic and bystander tissues that, despite intense investigation, are still poorly understood. Xu et al. (2013) now describe the unexpected ability of adipose tissue macrophages to buffer lipids released from obese adipocytes in a manner independent of inflammatory macrophage activation. PMID:24315364

  6. Biology of Bony Fish Macrophages

    PubMed Central

    Hodgkinson, Jordan W.; Grayfer, Leon; Belosevic, Miodrag

    2015-01-01

    Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation. PMID:26633534

  7. Novel treatment of equine odontoclastic tooth resorption and hypercementosis of incisor teeth in a 22-year-old Arabian mare.

    PubMed

    Grier-Lowe, Candace K; Anthony, James

    2015-08-01

    Equine odontoclastic tooth resorption and hypercementosis is a rarely reported condition in the incisor and canine teeth of older horses. Histologically, there is internal and external resorption of the tooth with formation of excessive cementum. Once lesions become infected or supragingival this condition is very painful. The clinical manifestation, diagnosis and treatment of hypercementosis in an Arabian mare are described.

  8. 1,25-Dihydroxyvitamin D3 stimulates rat osteoblastic cells to release a soluble factor that increases osteoclastic bone resorption.

    PubMed Central

    McSheehy, P M; Chambers, T J

    1987-01-01

    Although 1,25-dihydroxyvitamin D3 stimulates osteoclastic bone resorption in vivo and in organ culture, the mechanism by which it effects this stimulation is unknown. We have recently found that the agent does not stimulate resorption by osteoclasts mechanically disaggregated from bone and incubated on slices of cortical bone. This suggests that the osteoclasts were removed by disaggregation from the influence of some cell type, present in intact bone, that mediates hormone responsiveness. We therefore tested the ability of osteoblastic cells derived from neonatal rat calvariae and of cloned, hormone-responsive osteosarcoma cells (UMR106) to restore hormone responsiveness to unresponsive populations of osteoclasts. We found that osteoblastic cells from both sources induced a two- to fourfold stimulation of osteoclastic bone resorption in the presence of 1,25-dihydroxyvitamin D3. Stimulation was observed at concentrations of 10(-10) M and above. Actinomycin D and cycloheximide did not affect bone resorption by osteoclasts incubated alone, but abolished the capacity of osteoblastic cells to stimulate osteoclastic resorption in the presence of 1,25-dihydroxyvitamin D3. When calvarial cells or osteoblastlike UMR cells were incubated with the hormone, they produced a factor in cell-free supernatants that stimulated bone resorption by disaggregated osteoclasts. These experiments suggest that 1,25-dihydroxyvitamin D3 stimulates bone resorption through a primary action on osteoblastic cells, that are induced by the hormone to produce a factor that stimulates osteoclastic bone resorption. PMID:3611354

  9. Amiloride‐sensitive fluid resorption in NCI‐H441 lung epithelia depends on an apical Cl− conductance

    PubMed Central

    Korbmacher, Jonas P.; Michel, Christiane; Neubauer, Daniel; Thompson, Kristin; Mizaikoff, Boris; Frick, Manfred; Dietl, Paul; Wittekindt, Oliver H.

    2014-01-01

    Abstract Proper apical airway surface hydration is essential to maintain lung function. This hydration depends on well‐balanced water resorption and secretion. The mechanisms involved in resorption are still a matter of debate, especially as the measurement of transepithelial water transport remains challenging. In this study, we combined classical short circuit current (ISC) measurements with a novel D2O dilution method to correlate ion and water transport in order to reveal basic transport mechanisms in lung epithelia. D2O dilution method enabled precise analysis of water resorption with an unprecedented resolution. NCI‐H441 cells cultured at an air–liquid interface resorbed water at a rate of 1.5 ± 0.4 μL/(h cm2). Water resorption and ISC were reduced by almost 80% in the presence of the bulk Cl− channel inhibitor 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid (NPPB) or amiloride, a specific inhibitor of epithelial sodium channel (ENaC). However, water resorption and ISC were only moderately affected by forskolin or cystic fibrosis transmembrane regulator (CFTR) channel inhibitors (CFTRinh‐172 and glybenclamide). In line with previous studies, we demonstrate that water resorption depends on ENaC, and CFTR channels have only a minor but probably modulating effect on water resorption. However, the major ENaC‐mediated water resorption depends on an apical non‐CFTR Cl− conductance. PMID:24744880

  10. The Effect of Root Coating with Titanium on Prevention of Root Resorption in Avulsed Teeth: An Animal Study

    PubMed Central

    Heydari, Azar; Tahmasbi, Soodeh; Badiee, Mohammadreza; Izadi, SeyedSadra; Mashhadi Abbas, Fatemeh; Mokhtari, Sepideh

    2016-01-01

    Introduction: Tooth avulsion is a real dental emergency. If immediate replantation is not performed, the avulsed tooth may be lost due to inflammatory or replacement resorption. This animal study aimed to evaluate the bone response to the titanium coating of the root surface as an artificial barrier, and prevention of resorption of avulsed teeth. Methods and Materials: This experimental study was conducted on four male dogs. The dogs were randomly divided into two groups for assessment at two and eight weeks. Four teeth were extracted in each animal. The root surfaces of the test group were coated with a titanium layer using the Electron Beam Deposition system. After 24 h, replantation of the teeth was performed. Two animals were sacrificed after two weeks and the remaining dogs were killed after eight weeks. The presence of inflammation, inflammatory resorption, replacement resorption, periodontal regeneration, periapical granuloma and ankylosis were evaluated through histological analyses. Results: Inflammatory root resorption was not present in any tooth except one tooth in the coated group after eight weeks. Replacement resorption was noted just in three of the non-coated teeth after two weeks and two teeth after eight weeks. The McNemar's test revealed that the frequency of replacement resorption in the non-coated group was significantly higher than the coated group (P=0.031). Conclusion: Based on the results of this study, it seems that coating the root surfaces of avulsed teeth with titanium may control the replacement root resorption. PMID:27790261

  11. Novel treatment of equine odontoclastic tooth resorption and hypercementosis of incisor teeth in a 22-year-old Arabian mare

    PubMed Central

    Grier-Lowe, Candace K.; Anthony, James

    2015-01-01

    Equine odontoclastic tooth resorption and hypercementosis is a rarely reported condition in the incisor and canine teeth of older horses. Histologically, there is internal and external resorption of the tooth with formation of excessive cementum. Once lesions become infected or supragingival this condition is very painful. The clinical manifestation, diagnosis and treatment of hypercementosis in an Arabian mare are described. PMID:26246633

  12. Novel treatment of equine odontoclastic tooth resorption and hypercementosis of incisor teeth in a 22-year-old Arabian mare.

    PubMed

    Grier-Lowe, Candace K; Anthony, James

    2015-08-01

    Equine odontoclastic tooth resorption and hypercementosis is a rarely reported condition in the incisor and canine teeth of older horses. Histologically, there is internal and external resorption of the tooth with formation of excessive cementum. Once lesions become infected or supragingival this condition is very painful. The clinical manifestation, diagnosis and treatment of hypercementosis in an Arabian mare are described. PMID:26246633

  13. Novel Use of PRF and PDT in the Management of Trauma Induced Root Resorption and Infrabony Defect.

    PubMed

    Pruthi, Preeti Jain; Yadav, Neha; Nawal, Ruchika Roongta; Talwar, Sangeeta; Lamba, Arundeep Kaur

    2015-05-01

    Root resorption is a common squeal of traumatic injury to the dentition. Its progression can be minimized by early diagnosis and appropriate treatment. This case report presents the diagnosis and management of a case of trauma induced trio of apical root resorption, intraradicular root resorption and infrabony defect in maxillary central incisor. The main aim in treating such cases of resorption is to limit the inflammatory response at the periapical region so as to halt the resorptive process. To allow faster regeneration of the periodontal tissues, Platelet rich fibrin (PRF), a second generation platelet concentrate was used as an apical matrix over which MTA plug was given. The periodontal defect was managed with the help of localized antimicrobial photodynamic therapy (aPDT).

  14. Novel Use of PRF and PDT in the Management of Trauma Induced Root Resorption and Infrabony Defect

    PubMed Central

    Yadav, Neha; Nawal, Ruchika Roongta; Talwar, Sangeeta; Lamba, Arundeep Kaur

    2015-01-01

    Root resorption is a common squeal of traumatic injury to the dentition. Its progression can be minimized by early diagnosis and appropriate treatment. This case report presents the diagnosis and management of a case of trauma induced trio of apical root resorption, intraradicular root resorption and infrabony defect in maxillary central incisor. The main aim in treating such cases of resorption is to limit the inflammatory response at the periapical region so as to halt the resorptive process. To allow faster regeneration of the periodontal tissues, Platelet rich fibrin (PRF), a second generation platelet concentrate was used as an apical matrix over which MTA plug was given. The periodontal defect was managed with the help of localized antimicrobial photodynamic therapy (aPDT). PMID:26155584

  15. Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats.

    PubMed

    Kirschneck, Christian; Wolf, Michael; Reicheneder, Claudia; Wahlmann, Ulrich; Proff, Peter; Roemer, Piero

    2014-12-01

    The anchorage mechanisms currently used in orthodontic treatment have various disadvantages. The objective of this study was to determine the applicability of the osteoporosis medication strontium ranelate in pharmacologically induced orthodontic tooth anchorage. In 48 male Wistar rats, a constant orthodontic force of 0.25 N was reciprocally applied to the upper first molar and the incisors by means of a Sentalloy(®) closed coil spring for two to four weeks. 50% of the animals received strontium ranelate at a daily oral dosage of 900 mg per kilogramme of body weight. Bioavailability was determined by blood analyses. The extent of tooth movement was measured both optometrically and cephalometrically (CBCT). Relative alveolar gene expression of osteoclastic markers and OPG-RANKL was assessed by qRT-PCR and root resorption area and osteoclastic activity were determined in TRAP-stained histologic sections of the alveolar process. Compared to controls, the animals treated with strontium ranelate showed up to 40% less tooth movement after four weeks of orthodontic treatment. Gene expression and histologic analyses showed significantly less osteoclastic activity and a significantly smaller root resorption area. Blood analyses confirmed sufficient bioavailability of strontium ranelate. Because of its pharmacologic effects on bone metabolism, strontium ranelate significantly reduced tooth movement and root resorption in orthodontic treatment of rats. Strontium ranelate may be a viable agent for inducing tooth anchorage and reducing undesired root resorption in orthodontic treatment. Patients under medication of strontium ranelate have to expect prolonged orthodontic treatment times. PMID:25281203

  16. Management of a massive resorptive lesion with multiple perforations in a molar: case report.

    PubMed

    Borkar, Swati; de Noronha de Ataide, Ida

    2015-05-01

    Internal resorption is usually asymptomatic. Large resorption defects may result in penetration of the root dentin leading to perforation. In this case report, we describe the diagnosis and nonsurgical repair of a large resorptive lesion with multiple perforations in a mandibular first molar using cone-beam computed tomographic technology. The 3 different root perforations were located in the mesial root and repaired using Biodentine (Septodont, Saint-Maur des Fossés, France). The mesial root weakened from resorption was reinforced by replacing the lost root dentin with calcium silicate-based cement and placement of a glass fiber post. The 18-month follow-up confirmed remineralization of the osseous defect and asymptomatic function of the tooth. A further follow-up at 43 months revealed retention of the tooth and absence of root fracture. Usually, a tooth with multiple perforations and such a severe tooth material loss would have been destined for extraction. However, with contemporary diagnostic techniques such as cone-beam computed tomography and use of advanced biomaterials and root reinforcement methods, such teeth can be salvaged.

  17. Conservative Management of Class 4 Invasive Cervical Root Resorption Using Calcium-enriched Mixture Cement.

    PubMed

    Asgary, Saeed; Nosrat, Ali

    2016-08-01

    Class 4 invasive cervical root resorption (ICRR) presents a treatment dilemma in endodontics. The widely accepted treatment options for a class 4 ICRR are to leave these teeth untreated for as long as they are asymptomatic or extraction. This report presents a conservative approach for the management of class 4 ICRR. A 28-year-old woman was referred for root canal treatment of tooth #26. The patient had a history of orthodontic treatment. Radiographic evaluation showed class 4 ICRR that had perforated the root canal space, a radiolucent crestal bony defect, and a periapical lesion. Clinically, a deep (6-mm) probing area was found on the mesial side of the tooth that bled on probing. The tooth was sensitive to percussion. After the treatment options were discussed with the patient, she chose to save the tooth. After complete chemomechanical preparation of the root canal, the entire canal space and perforation area were filled with calcium-enriched mixture cement. No attempt was made to mechanically remove the resorptive lacuna. Twenty four months after treatment, the tooth was functional and asymptomatic, and probing was within normal limits (<3 mm) with no bleeding during probing. Radiographic examination revealed no progression of resorption, osseous healing of the crestal bony defect, and healing of the periapical lesion. Obturation of the root canal space with calcium-enriched mixture cement may be a viable treatment option for an otherwise non-treatable tooth with class 4 invasive cervical root resorption. PMID:27316319

  18. Osteoclastogenesis and Osteoclastic Resorption of Tricalcium Phosphate: Effect of Strontium and Magnesium Doping

    PubMed Central

    Roy, Mangal; Bose, Susmita

    2012-01-01

    Bone substitute materials are required to support the remodeling process, which consists of osteoclastic resorption and osteoblastic synthesis. Osteoclasts, the bone resorbing cells, generate from differentiation of hemopoietic mononuclear cells. In the present study we have evaluated the effects of 1.0 wt% strontium (Sr) and 1.0 wt% magnesium (Mg) doping in beta-tricalcium phosphate (β-TCP) on the differentiation of mononuclear cells into osteoclast-like cells and its resorptive activity. In vitro osteoclast-like cell formation, adhesion, and resorption were studied using osteoclast precursor RAW 264.7 cell, supplemented with receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast-like cell formation was noticed on pure and Sr doped β-TCP samples at day 8 which was absent on Mg doped β-TCP samples indicating decrease in initial osteoclast differentiation due to Mg doping. After 21 days of culture, osteoclast-like cell formation was evident on all samples with osteoclastic markers such as actin ring, multiple nuclei, and presence of vitronectin receptor αvβ3 integrin. After osteoclast differentiation, all substrates showed osteoclast-like cell mediated degradation, however; significantly restricted for Mg doped β-TCP samples. Our present results indicated substrate chemistry controlled osteoclast differentiation and resorptive activity which can be used in designing TCP based resorbable bone substitutes with controlled degradation properties. PMID:22566212

  19. Optical and scanning electron microscopy in the single osteoclast resorption assay.

    PubMed

    Boyde, A; Ali, N N; Jones, S J

    1985-01-01

    The present studies relate to the single or isolated osteoclastic resorption function assay which we introduced in 1983 to overcome objections to assays based upon measurements of calcium release from bones, in which it was never strictly controlled whether the mechanism involved the destruction of bone with the formation of classical Howship's lacunae. The method may prove to be quite popular in the near future and has already been adopted by other research groups. In previous work, we had utilised stereophotogrammetry of scanning electron micrographs to measure the depth, volume and other parameters of the individual lacunae. However, increasing experience with the method has suggested that we can await a wide range of biological variability in single cell function in any one experiment. We have therefore tested other methods from which data could be obtained more rapidly to permit a better statistical analysis, albeit with reduced accuracy, of each resorption complex. The main aim of the studies reported here was to evaluate various methods of optical and scanning electron microscopy that can be used for the visualization of osteoclasts and their associated resorption lacunae generated in vitro in slabs of dentine and bone. Optical microscopy was found to be complementary to SEM, enabling vital microscopy of unstained and stained cells. In particular, oblique illumination LM and tandem scanning reflected LM (TSRLM) proved to be of paramount value for this purpose. Fixed coated specimens could be most rapidly scanned for resorption lacunae using darkfield reflected LM or TSRLM.

  20. Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase.

    PubMed Central

    Kasten, T P; Collin-Osdoby, P; Patel, N; Osdoby, P; Krukowski, M; Misko, T P; Settle, S L; Currie, M G; Nickols, G A

    1994-01-01

    We have examined the effects of modulating nitric oxide (NO) levels on osteoclast-mediated bone resorption in vitro and the effects of nitric oxide synthase (NOS) inhibitors on bone mineral density in vivo. Diaphorase-based histochemical staining for NOS activity of bone sections or highly enriched osteoclast cultures suggested that osteoclasts exhibit substantial NOS activity that may account for basal NO production. Chicken osteoclasts were cultured for 36 hr on bovine bone slices in the presence or absence of the NO-generating agent sodium nitroprusside or the NOS inhibitors N-nitro-L-arginine methyl ester and aminoguanidine. Nitroprusside markedly decreased the number of bone pits and the average pit area in comparison with control cultures. On the other hand, NOS inhibition by N-nitro-L-arginine methyl ester or aminoguanidine dramatically increased the number of bone pits and the average resorption area per pit. In a model of osteoporosis, aminoguanidine potentiated the loss of bone mineral density in ovariectomized rats. Aminoguanidine also caused a loss of bone mineral density in the sham-operated rats. Inhibition of NOS activity in vitro and in vivo resulted in an apparent potentiation of osteoclast activity. These findings suggest that endogenous NO production in osteoclast cultures may regulate resorption activity. The modulation of NOS and NO levels by cells within the bone microenvironment may be a sensitive mechanism for local control of osteoclast bone resorption. Images PMID:7513424

  1. Localized idiopathic root resorption in the primary dentition: Review of the literature and a case report.

    PubMed

    Nasehi, Atefeh; Mazhari, Fatemeh; Mohtasham, Nooshin

    2015-01-01

    Idiopathic root resorption (IRR) is an infrequent condition that is usually found as an accidental finding on radiography. A significant number of cases of IRR in permanent dentition have been presented but are rarely reported in primary dentition. The aim of this case report is to present a case of localized IRR in a 7-year-old boy. The patient was referred because of increased mobility of the left mandibular primary second molar. On radiographic evaluation, severe root resorption of that tooth, and mild root resorption of the right mandibular primary second molar were evident; the patient was caries-free. The left affected tooth was lost, and after placing a band and loop space maintainer, the patient was followed for 18 months. A patient with an abnormal pattern of root resorption, especially in the primary dentition, should alert the clinician to rule out the known important local and systemic factors. The exact causes of and treatments for IRR continue to be discovered.

  2. Localized idiopathic root resorption in the primary dentition: Review of the literature and a case report

    PubMed Central

    Nasehi, Atefeh; Mazhari, Fatemeh; Mohtasham, Nooshin

    2015-01-01

    Idiopathic root resorption (IRR) is an infrequent condition that is usually found as an accidental finding on radiography. A significant number of cases of IRR in permanent dentition have been presented but are rarely reported in primary dentition. The aim of this case report is to present a case of localized IRR in a 7-year-old boy. The patient was referred because of increased mobility of the left mandibular primary second molar. On radiographic evaluation, severe root resorption of that tooth, and mild root resorption of the right mandibular primary second molar were evident; the patient was caries-free. The left affected tooth was lost, and after placing a band and loop space maintainer, the patient was followed for 18 months. A patient with an abnormal pattern of root resorption, especially in the primary dentition, should alert the clinician to rule out the known important local and systemic factors. The exact causes of and treatments for IRR continue to be discovered. PMID:26929703

  3. Impairment of osteoclastic bone resorption in rapidly growing female p47phox knockout mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone formation is dependent on the activity and differentiation of osteoblasts; whereas resorption of preexisting mineralized bone matrix by osteoclasts is necessary not only for bone development but also for regeneration and remodeling. Bone remodeling is a process in which osteoblasts and osteocla...

  4. Soil nitrogen affects phosphorus recycling: foliar resorption and plant-soil feedbacks in a northern hardwood forest.

    PubMed

    See, Craig R; Yanai, Ruth D; Fisk, Melany C; Vadeboncoeur, Matthew A; Quintero, Brauuo A; Fahey, Timothy J

    2015-09-01

    Previous studies have attempted to link foliar resorption of nitrogen and phosphorus to their. respective availabilities in soil, with mixed results. Based on resource optimization theory, we hypothesized that the foliar resorption of one element could be driven by the availability of another element. We tested various measures of soil N and P as predictors of N and P resorption in six tree species in 18 plots across six stands at the Bartlett Experimental Forest, New Hampshire, USA. Phosphorus resorption efficiency (P < 0.01) and proficiency (P = 0.01) increased with soil N content. to 30 cm depth, suggesting that trees conserve P based on the availability of soil N. Phosphorus resorption also increased with soil P content, which is difficult to explain basdd on single-element limitation, butfollows from the correlation between soil N and soil P. The expected single-element relationships were evident only in the 0 horizon: P resorption was high where resin-available P was low in the Oe (P < 0.01 for efficiency, P < 0.001 for proficiency) and N resorption was high where potential N mineralization in the Oa was low (P < 0.01 for efficiency and 0.11 for proficiency). Since leaf litter is a principal source of N and P to the 0 horizon, low nutrient availability there could be a result rather than a cause of high resorption. The striking effect of soil N content on foliar P resorption is the first evidence of multiple-element control on nutrient resorption to be reported from an unmanipulated ecosystem.

  5. Inhibition of osteoclast bone resorption activity through osteoprotegerin-induced damage of the sealing zone.

    PubMed

    Song, Ruilong; Gu, Jianhong; Liu, Xuezhong; Zhu, Jiaqiao; Wang, Qichao; Gao, Qian; Zhang, Jiaming; Cheng, Laiyang; Tong, Xishuai; Qi, Xinyi; Yuan, Yan; Liu, Zongping

    2014-09-01

    Bone remodeling is dependent on the dynamic equilibrium between osteoclast-mediated bone resorption and osteoblast-mediated osteogenesis. The sealing zone is an osteoclast-specific cytoskeletal structure, the integrity of which is critical for osteoclast-mediated bone resorption. To date, studies have focused mainly on the osteoprotegerin (OPG)‑induced inhibition of osteoclast differentiation through the OPG/receptor activator of the nuclear factor kappa-B ligand (RANKL)/RANK system, which affects the bone resorption of osteoclasts. However, the effects of OPG on the sealing zone have not been reported to date. In this study, the formation of the sealing zone was observed by Hoffman modulation contrast (HMC) microscopy and confocal laser scanning microscopy. The effects of OPG on the existing sealing zone and osteoclast-mediated bone resorption activity, as well as the regulatory role of genes involved in the formation of the sealing zone were examined by immunofluorescence staining, HMC microscopy, quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot analysis and scanning electron microscopy. The sealing zone was formed on day 5, with belt-like protuberances at the cell edge and scattered distribution of cell nuclei, but no filopodia. The sealing zone was intact in the untreated control group. However, defects in the sealing zone were observed in the OPG-treated group (20 ng/ml) and the structure was absent in the groups treated with 40 and 80 ng/ml OPG. The podosomes showed a scattered or clustered distribution between the basal surface of the osteoclasts and the well surface. Furthermore, resorption lacunae were not detected in the 20 ng/ml OPG-treated group, indicating the loss of osteoclast-mediated bone resorption activity. Treatment with OPG resulted in a significant decrease in the expression of Arhgef8/Net1 and DOCK5 Rho guanine nucleotide exchange factors (RhoGEFs), 10 of 18 RhoGTPases (RhoA, RhoB, cdc42v1, cdc42v2

  6. Metabolic Reprograming in Macrophage Polarization

    PubMed Central

    Galván-Peña, Silvia; O’Neill, Luke A. J.

    2014-01-01

    Studying the metabolism of immune cells in recent years has emphasized the tight link existing between the metabolic state and the phenotype of these cells. Macrophages in particular are a good example of this phenomenon. Whether the macrophage obtains its energy through glycolysis or through oxidative metabolism can give rise to different phenotypes. Classically activated or M1 macrophages are key players of the first line of defense against bacterial infections and are known to obtain energy through glycolysis. Alternatively activated or M2 macrophages on the other hand are involved in tissue repair and wound healing and use oxidative metabolism to fuel their longer-term functions. Metabolic intermediates, however, are not just a source of energy but can be directly implicated in a particular macrophage phenotype. In M1 macrophages, the Krebs cycle intermediate succinate regulates HIF1α, which is responsible for driving the sustained production of the pro-inflammatory cytokine IL1β. In M2 macrophages, the sedoheptulose kinase carbohydrate kinase-like protein is critical for regulating the pentose phosphate pathway. The potential to target these events and impact on disease is an exciting prospect. PMID:25228902

  7. Changes in Bone Resorption Across the Menopause Transition: Effects of Reproductive Hormones, Body Size, and Ethnicity

    PubMed Central

    Sowers, MaryFran R.; Zheng, Huiyong; Greendale, Gail A.; Neer, Robert M.; Cauley, Jane A.; Ellis, Jayne; Johnson, Sarah

    2013-01-01

    Objective: Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. Methods: Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. Results: Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m2 and smallest in women with BMI >30 kg/m2. Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. Summary: During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss. PMID:23666961

  8. Assessment of global morphological and topological changes in trabecular structure under the bone resorption process

    NASA Astrophysics Data System (ADS)

    Sidorenko, Irina N.; Bauer, Jan; Monetti, Roberto; Baum, Thomas; Rummeny, Ernst J.; Eckstein, Felix; Matsuura, Maiko; Lochmueller, Eva-Maria; Zysset, Philippe K.; Raeth, Christoph W.

    2012-03-01

    Osteoporosis is a frequent skeletal disease characterised both by loss of bone mineral mass and deterioration of cancellous bone micro-architecture. It can be caused by mechanical disuse, estrogen deficiency or natural age-related resorption process. Numerical analysis of high-resolution images of the trabecular network is recognised as a powerful tool for assessment of structural characteristics. Using μCT images of 73 thoracic and 78 lumbar human vertebral specimens in vitro with isotropic resolution of 26μm we simulate bone atrophy as random resorption of bone surface voxels. Global morphological and topological characteristics provided by four Minkowski Functionals (MF) are calculated for two numerical resorption models with and without conservation of global topological connectivity of the trabecular network, which simulates different types of bone loss in osteoporosis, as it has been described in males and females. Diagnostic performance of morphological and topological characteristics as a function of relative bone loss is evaluated by a correlation analysis with respect to experimentally measured Maximum Compressive Strength (MCS). In both resorption models the second MF, which coincides with bone surface fraction BS/TV, demonstrates almost constant value of Pearson's correlation coefficient with respect to the relative bone loss ▵BV/TV. This morphological characteristic does not vary considerably under age-related random resorption and can be used for predicting bone strength in the elderly. The third and fourth MF demonstrate an increasing correlation coefficients with MCS after applying random bone surface thinning without preserving topological connectivity, what can be used for improvement of evaluation of the current state of the structure.

  9. The relevance of leukotrienes for bone resorption induced by mechanical loading.

    PubMed

    Moura, A P; Taddei, S R A; Queiroz-Junior, C M; Madeira, M F M; Rodrigues, L F D; Garlet, G P; Souza, D G; Machado, F S; Andrade, I; Teixeira, M M; Silva, T A

    2014-12-01

    5-Lipoxygenase (5-LO) metabolites are important pro-inflammatory lipid mediators. However, much still remains to be understood about the role of such mediators in bone remodeling. This study aimed to investigate the effect of 5-LO metabolites, LTB4 and CysLTs, in a model of mechanical loading-induced bone remodeling. Strain-induced tooth movement and consequently alveolar bone resorption/apposition was achieved by using a coil spring placed on molar and attached to incisors of C57BL6 (wild-type-WT), 5-LO deficient mice (5-LO(-/-)) and mice treated with 5-LO inhibitor (zileuton-ZN) or with antagonist of CysLTs receptor (montelukast-MT). The amount of bone resorption and the number of osteoclasts were determined morphometrically. The expression of inflammatory and bone remodeling markers in periodontium was analyzed by qPCR. Osteoclast differentiation and TNF-α production were evaluated in vitro using RAW 264.7 cells treated with LTB4 or LTD4. Bone resorption, TRAP(+) cells and expression of Tnfa, Il10 and Runx2 were significantly diminished in 5-LO(-/-), ZN- and MT-treated mice. The expression of Rank was also reduced in 5-LO(-/-) and MT-treated mice. Accordingly, LTB4 and LTD4 in association with RANKL promoted osteoclast differentiation and increased TNF-α release in vitro. These data demonstrate that the absence of 5-LO metabolites, LTB4 and CysLTs reduces osteoclast recruitment and differentiation, consequently diminishing bone resorption induced by mechanical loading. Thus, 5-LO might be a potential target for controlling bone resorption in physiological and pathological conditions. PMID:25270168

  10. Effects of Zinc and Strontium Substitution in Tricalcium Phosphate on Osteoclast Differentiation and Resorption

    PubMed Central

    Roy, Mangal; Fielding, Gary; Bandyopadhyay, Amit; Bose, Susmita

    2013-01-01

    Bone replacement materials must be able to regulate both osteoblastic synthesis of new bone and osteoclastic resorption process in order to maintain the balance of bone remodeling. Osteoclasts generate from differentiation of mononuclear cells. In the present study, we have studied the osteoclast-like-cells responses (differentiation from mononuclear cells and resorption) to beta tricalcium phosphate (β-TCP) doped with zinc (Zn) and strontium (Sr). Osteoclast-like-cells differentiation and resorption was studied in vitro using osteoclast-like-cells precursor RAW 264.7 cell, supplemented with receptor activator of nuclear factor κβ ligand (RANKL). Morphological and immunohistochemical analysis confirmed successful differentiation of osteoclast-like-cells on the doped and undoped β-TCP substrates after 8 days of culture. Cells on the substrate surface expressed specific osteoclast markers such as; actin ring, multiple nucleus, tartrate-resistant acid phosphatase (TRAP) synthesis, and vitronectin receptor. However, quantitative TRAP assay indicated the inhibiting effect of Zn on osteoclast differentiation. Although, Zn doped β-TCP restricted osteoclast-like-cells differentiation, the samples were resorbed much faster. An increased resorption pit volume was noticed on Zn doped β-TCP samples after 28 days of culture compared to pure and Sr doped β-TCP. In this work, we demonstrated that β-TCP bone substitute materials can be successfully resorbed by osteoclast-like-cells, where both osteoclast-like-cells differentiation and resorption were modulated by Zn and/or Sr doping- a much needed property for successful bone remodeling. PMID:24244866

  11. The Effect of An Angiogenic Cytokine on Orthodontically Induced Inflammatory Root Resorption

    PubMed Central

    Seifi, Massoud; Lotfi, Ali; Badiee, Mohammad Reza; Abdolazimi, Zahra; Amdjadi, Parisa; Bargrizan, Majid

    2016-01-01

    Objective Orthodontically induced inflammatory root resorption (OIIRR) is an undesirable sequel of tooth movement after sterile necrosis that takes place in periodontal ligament due to blockage of blood vessels following exertion of orthodontic force. This study sought to assess the effect of an angiogenic cytokine on OIIRR in rat model. Materials and Methods In this experimental animal study, 50 rats were randomly divided into 5 groups of 10 each: E10, E100 and E1000 receiving an injection of 10, 100 and 1000 ng of basic fibroblast growth factor (bFGF), respectively, positive control group (CP) receiving an orthodontic appliance and injection of phosphate buffered saline (PBS) and the negative control group (CN) receiving only the anesthetic agent. A nickel titanium coil spring was placed between the first molar and the incisor on the right side of maxilla. Twenty-one days later, the rats were sacrificed. Histopathological sections were made to assess the number and area of resorption lacunae, number of blood vessels, osteoclasts and Howship’s lacunae. Data were statistically analyzed using ANOVA and Tukey’s honest significant difference (HSD) test. Results Number of resorption lacunae and area of resorption lacunae in E1000 (0.97 ± 0.80 and 1. 27 ± 0.01×10-3, respectively) were significantly lower than in CP (4.17 ± 0.90 and 2.77 ± 0.01×10-3, respectively, P=0.000). Number of blood vessels, osteoclasts and Howship’s lacunae were significantly higher in E1000 compared to CP (P<0.05). Conclusion Tooth movement as the outcome of bone remodeling is concomitant with the formation of sterile necrosis in the periodontal ligament following blocked blood supply. Thus, bFGF can significantly decrease the risk of root resorption by providing more oxygen and angiogenesis. PMID:27551674

  12. Combined effects of nitrogen addition and litter manipulation on nutrient resorption of Leymus chinensis in a semi-arid grassland of northern China.

    PubMed

    Li, X; Liu, J; Fan, J; Ma, Y; Ding, S; Zhong, Z; Wang, D

    2015-01-01

    Plant growth in semi-arid ecosystems is usually severely limited by soil nutrient availability. Alleviation of these resource stresses by fertiliser application and aboveground litter input may affect plant internal nutrient cycling in such regions. We conducted a 4-year field experiment to investigate the effects of nitrogen (N) addition (10 g N·m(-2) ·year(-1)) and plant litter manipulation on nutrient resorption of Leymus chinensis, the dominant native grass in a semi-arid grassland in northern China. Although N addition had no clear effects on N and phosphorus (P) resorption efficiencies in leaves and culms, N fertilisation generally decreased leaf N resorption proficiency by 54%, culm N resorption proficiency by 65%. Moreover, N fertilisation increased leaf P resorption proficiency by 13%, culm P resorption proficiency by 20%. Under ambient or enriched N conditions, litter addition reduced N and P resorption proficiencies in both leaves and culms. The response of P resorption proficiency to litter manipulation was more sensitive than N resorption proficiency: P resorption proficiency in leaves and culms decreased strongly with increasing litter amount under both ambient and enriched N conditions. In contrast, N resorption proficiency was not significantly affected by litter addition, except for leaf N resorption proficiency under ambient N conditions. Furthermore, although litter addition caused a general decrease of leaf and culm nutrient resorption efficiencies under both ambient and enriched N conditions, litter addition effects on nutrient resorption efficiency were much weaker than the effects of litter addition on nutrient resorption proficiency. Taken together, our results show that leaf and non-leaf organs of L. chinensis respond consistently to altered soil N availability. Our study confirms the strong effects of N addition on plant nutrient resorption processes and the potential role of aboveground litter, the most important natural fertiliser in

  13. Macrophages and the Viral Dissemination Super Highway

    PubMed Central

    Klepper, Arielle; Branch, Andrea D

    2016-01-01

    Monocytes and macrophages are key components of the innate immune system yet they are often the victims of attack by infectious agents. This review examines the significance of viral infection of macrophages. The central hypothesis is that macrophage tropism enhances viral dissemination and persistence, but these changes may come at the cost of reduced replication in cells other than macrophages. PMID:26949751

  14. Cellular metabolism and macrophage functional polarization.

    PubMed

    Zhu, Linnan; Zhao, Qingjie; Yang, Tao; Ding, Wenjun; Zhao, Yong

    2015-01-01

    Macrophages are a functionally heterogeneous cell population that is mainly shaped by a variety of microenvironmental stimuli. Interferon γ (IFN-γ), interleukin-1β (IL-1β), and lipopolysaccharide (LPS) induce a classical activation of macrophages (M1), whereas IL-4 and IL-13 induce an alternative activation program in macrophages (M2). Reprogramming of intracellular metabolisms is required for the proper polarization and functions of activated macrophages. Similar to the Warburg effect observed in tumor cells, M1 macrophages increase glucose consumption and lactate release and decreased oxygen consumption rate. In comparison, M2 macrophages mainly employ oxidative glucose metabolism pathways. In addition, fatty acids, vitamins, and iron metabolisms are also related to macrophage polarization. However, detailed metabolic pathways involved in macrophages have remained elusive. Understanding the bidirectional interactions between cellular metabolism and macrophage functions in physiological and pathological situations and the regulatory pathways involved may offer novel therapies for macrophage-associated diseases.

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

    PubMed

    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

  16. Deletion of FGFR3 in Osteoclast Lineage Cells Results in Increased Bone Mass in Mice by Inhibiting Osteoclastic Bone Resorption.

    PubMed

    Su, Nan; Li, Xiaogang; Tang, Yubin; Yang, Jing; Wen, Xuan; Guo, Jingyuan; Tang, Junzhou; Du, Xiaolan; Chen, Lin

    2016-09-01

    Fibroblast growth factor receptor 3 (FGFR3) participates in bone remodeling. Both Fgfr3 global knockout and activated mice showed decreased bone mass with increased osteoclast formation or bone resorption activity. To clarify the direct effect of FGFR3 on osteoclasts, we specifically deleted Fgfr3 in osteoclast lineage cells. Adult mice with Fgfr3 deficiency in osteoclast lineage cells (mutant [MUT]) showed increased bone mass. In a drilled-hole defect model, the bone remodeling of the holed area in cortical bone was also impaired with delayed resorption of residual woven bone in MUT mice. In vitro assay demonstrated that there was no significant difference between the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts derived from wild-type and Fgfr3-deficient bone marrow monocytes, suggesting that FGFR3 had no remarkable effect on osteoclast formation. The bone resorption activity of Fgfr3-deficient osteoclasts was markedly decreased accompanying with downregulated expressions of Trap, Ctsk, and Mmp 9. The upregulated activity of osteoclastic bone resorption by FGF2 in vitro was also impaired in Fgfr3-deficient osteoclasts, indicating that FGFR3 may participate in the regulation of bone resorption activity of osteoclasts by FGF2. Reduced adhesion but not migration in osteoclasts with Fgfr3 deficiency may be responsible for the impaired bone resorption activity. Our study for the first time genetically shows the direct positive regulation of FGFR3 on osteoclastic bone resorption. © 2016 American Society for Bone and Mineral Research.

  17. Deletion of FGFR3 in Osteoclast Lineage Cells Results in Increased Bone Mass in Mice by Inhibiting Osteoclastic Bone Resorption.

    PubMed

    Su, Nan; Li, Xiaogang; Tang, Yubin; Yang, Jing; Wen, Xuan; Guo, Jingyuan; Tang, Junzhou; Du, Xiaolan; Chen, Lin

    2016-09-01

    Fibroblast growth factor receptor 3 (FGFR3) participates in bone remodeling. Both Fgfr3 global knockout and activated mice showed decreased bone mass with increased osteoclast formation or bone resorption activity. To clarify the direct effect of FGFR3 on osteoclasts, we specifically deleted Fgfr3 in osteoclast lineage cells. Adult mice with Fgfr3 deficiency in osteoclast lineage cells (mutant [MUT]) showed increased bone mass. In a drilled-hole defect model, the bone remodeling of the holed area in cortical bone was also impaired with delayed resorption of residual woven bone in MUT mice. In vitro assay demonstrated that there was no significant difference between the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts derived from wild-type and Fgfr3-deficient bone marrow monocytes, suggesting that FGFR3 had no remarkable effect on osteoclast formation. The bone resorption activity of Fgfr3-deficient osteoclasts was markedly decreased accompanying with downregulated expressions of Trap, Ctsk, and Mmp 9. The upregulated activity of osteoclastic bone resorption by FGF2 in vitro was also impaired in Fgfr3-deficient osteoclasts, indicating that FGFR3 may participate in the regulation of bone resorption activity of osteoclasts by FGF2. Reduced adhesion but not migration in osteoclasts with Fgfr3 deficiency may be responsible for the impaired bone resorption activity. Our study for the first time genetically shows the direct positive regulation of FGFR3 on osteoclastic bone resorption. © 2016 American Society for Bone and Mineral Research. PMID:26990430

  18. Three-dimensional analysis of alveolar bone resorption by image processing of 3-D dental CT images

    NASA Astrophysics Data System (ADS)

    Nagao, Jiro; Kitasaka, Takayuki; Mori, Kensaku; Suenaga, Yasuhito; Yamada, Shohzoh; Naitoh, Munetaka

    2006-03-01

    We have developed a novel system that provides total support for assessment of alveolar bone resorption, caused by periodontitis, based on three-dimensional (3-D) dental CT images. In spite of the difficulty in perceiving the complex 3-D shape of resorption, dentists assessing resorption location and severity have been relying on two-dimensional radiography and probing, which merely provides one-dimensional information (depth) about resorption shape. However, there has been little work on assisting assessment of the disease by 3-D image processing and visualization techniques. This work provides quantitative evaluation results and figures for our system that measures the three-dimensional shape and spread of resorption. It has the following functions: (1) measures the depth of resorption by virtually simulating probing in the 3-D CT images, taking advantage of image processing of not suffering obstruction by teeth on the inter-proximal sides and much smaller measurement intervals than the conventional examination; (2) visualizes the disposition of the depth by movies and graphs; (3) produces a quantitative index and intuitive visual representation of the spread of resorption in the inter-radicular region in terms of area; and (4) calculates the volume of resorption as another severity index in the inter-radicular region and the region outside it. Experimental results in two cases of 3-D dental CT images and a comparison of the results with the clinical examination results and experts' measurements of the corresponding patients confirmed that the proposed system gives satisfying results, including 0.1 to 0.6mm of resorption measurement (probing) error and fairly intuitive presentation of measurement and calculation results.

  19. Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R

    PubMed Central

    LIU, SHUANGXIN; ZHU, WEIPING; LI, SIJIA; MA, JIANCHAO; ZHANG, HUITAO; LI, ZHONGHE; ZHANG, LI; ZHANG, BIN; LI, ZHUO; LIANG, XINLING; SHI, WEI

    2016-01-01

    The vacuolar-type H+ adenosine triphosphatase (V-ATPase) plays an important role in cellular acidification and bone resorption by osteoclasts. However, the direct effect of bovine parathyroid hormone (bPTH) on V-ATPase has not yet been elucidated. The aim of the present study was to assess the effects of bPTH on V-ATPase and osteoclasts. Osteoclasts from bone marrow (BM)-derived monocytes of C57BL/6 mice were cultured with or without bPTH. The mRNA and protein expression levels of the V-ATPase a3-subunit and d2-subunit (by RT-qPCR and western blot analysis), V-ATPase activity (using the V type ATPase Activity Assay kit) and the bone resorption function of osteoclasts (by bone resorption assay) were examined following treatment with various concentrations of bPTH (0.1, 1.0, 10 and 100 ng/ml) alone or with bPTH and its inhibitor, bafilomycin A1. Furthermore, the expression of parathyroid hormone (PTH) receptors in osteoclasts was also detected. The results revealed that the mRNA and protein expression levels of V-ATPase a3-subunit and d2-subunit increased in a dose-dependent manner, paralleling the level of bPTH present. In addition, an increase in the concentration of bPTH was accompanied by the increased resorption capability of osteoclasts, whereas bone resorption was inhibited in the presence of bafilomycin A1. In addition, we confirmed the existence of parathyroid hormone 1 receptor (PTH1R) in osteoclasts using three different methods (RT-qPCR, western blot analysis and immunofluorescence staining). We found that bPTH enhanced the bone resorption capability of osteoclasts by modulating the expression of V-ATPase subunits, intracellular acidification and V-ATPase activity. Thus, we propose that PTH has a direct effect on osteoblasts and osteoclasts, and that this effect is mediated through PTH1R, thus contributing to bone remodeling. PMID:26647715

  20. Dimensional analysis of osteoclastic bone resorption and the measurement of biologically active calcitonin.

    PubMed

    Zaidi, M; Bax, B E; Shankar, V S; Moonga, B S; Simon, B; Alam, A S; Gaines Das, R E; Pazianas, M; Huang, C L

    1994-05-01

    Calcitonin inhibits bone resorption through a direct action on the osteoclast. We report a quantitative analysis of bone resorption by disaggregated rat osteoclasts. We then used our findings to develop a formal bioassay for calcitonin. Osteoclasts were mechanically disaggregated from neonatal rat long bones and dispersed at low densities on slices of devitalized bovine cortical bone. The resulting areas of bone excavation were quantified to micrometric precision by scanning electron microscopy together with computer-assisted image analysis. These findings were correlated with the volumes of bone resorption in the same slices measured by confocal scanning microscopy for the first time. The total planar areas of bone resorption per slice correlated linearly (r = 0.78) with the confocal microscopic measurements of total volume resorbed, provided that volume was expressed to its two-thirds power. The latter transformation resulted in representations of the determined areas ([length]2) and volumes ([length]3) which were dimensionally consistent. These findings thus demonstrate that osteoclastic bone excavations show a consistent relationship between area and volume and that assessments of the area of excavations accordingly provide an empirical representation of the volume of bone resorbed. Furthermore, in view of the skewed nature of the distributions of area measurements, we assessed the effect of transforming the response variable to derive a metameter, (planar area of resorption)1/2. Such transformed data points, which expressed the data in the dimensions of [length], were more normally distributed than the raw data points and had more stable variances over a wider concentration range. We accordingly determined relative potencies using parallel line analyses on the transformed data. The latter offered a consistent correlation to the volume measurements when these were also converted to dimensions of [length] (r = 0.805). It was confirmed that the inhibition of bone

  1. Contrasting effects of an aminobisphosphonate, a potent inhibitor of bone resorption, on lipopolysaccharide-induced production of interleukin-1 and tumour necrosis factor α in mice

    PubMed Central

    Sugawara, Shunji; Shibazaki, Masahiko; Takada, Haruhiko; Kosugi, Hiroshi; Endo, Yasuo

    1998-01-01

    Aminobisphosphonates (aminoBPs), potent inhibitors of bone resorption, have been reported to induce inflammatory reactions such as fever and an increase in acute phase proteins in human patients, and to induce the histamine-forming enzyme, histidine decarboxylase, in mice. In the present study, we examined the effect of aminoBP, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP), on the production of the pro-inflammatory cytokines, IL-1 and TNFα, in mice.Intraperitoneal injection of AHBuBP did not itself produce detectable levels of IL-1 (α and β) and TNFα in the serum. However, the elevation of serum IL-1 induced by lipopolysaccharide (LPS) was greatly augmented in mice injected with AHBuBP 3 days before the LPS injection, whereas the LPS-induced elevation of serum TNFα was almost completely abolished.Spleen and bone marrow cells taken from mice injected with AHBuBP produced IL-1β in vitro spontaneously, and the production was augmented following the addition of LPS. Cells that accumulated in the peritoneal cavity in response to AHBuBP produced a particularly large amount of IL-1β. However, AHBuBP treatment of mice did not lead to an impairment of the in vitro production of TNFα by these three types of cells.Liposomes encapsulating dichloromethylene bisphosphonate (a non-amino BP) selectively deplete phagocytic macrophages. When an intraperitoneal injection of these liposomes was given 2 days after an injection of AHBuBP, there was a marked decrease in the LPS-induced elevation of serum IL-1 (α and β) (LPS being injected 3 days after the injection of AHBuBP).These results indicate that AHBuBP has contrasting effects on the in vivo LPS-induced production of IL-1 and TNFα in mice, enhancing the production of IL-1 by phagocytic macrophages and suppressing the production of TNFα, although underling mechanisms remain to be clarified. PMID:9831909

  2. Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice.

    PubMed

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

    2015-01-01

    Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo.

  3. Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice

    PubMed Central

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M.W.; Miyaura, Chisato; Inada, Masaki

    2015-01-01

    Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo. PMID:26155460

  4. Heterotopic new bone formation causes resorption of the inductive bone matrix

    SciTech Connect

    Nilsson, O.S.; Persson, P.E.; Ekelund, A. )

    1990-08-01

    The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM.

  5. Interdisciplinary Approach for Management of Iatrogenic Internal Root Resorption: A Case Report

    PubMed Central

    Ramazani, Mohsen; Asgary, Saeed; Zarenejad, Nafiseh; Mehrani, Javad

    2016-01-01

    For management of a symptomatic maxillary lateral incisor with dull pain on chewing, suppurative sinus tract, defective metal-ceramic crown and iatrogenic internal root resorption, an interdisciplinary approach was taken. Two-visit nonsurgical treatment with calcium-enriched mixture (CEM) cement, replacement of metal-ceramic crown with all-ceramic crown and corrective periodontal plastic surgery were included in the treatment plan. Six-month and one-year follow-ups revealed complete resolution of signs and symptoms and radiographic healing. This case report highlights the importance of adequate cooling during crown preparation to preserve the pulp vitality and prevent internal resorptive lesions and also the profound sealing ability and biocompatibility of CEM cement. PMID:26843882

  6. CBCT Post-Processing Tools to Manage the Progression of Invasive Cervical Resorption: A Case Report.

    PubMed

    Vasconcelos, Karla de Faria; de-Azevedo-Vaz, Sergio Lins; Freitas, Deborah Queiroz; Haiter-Neto, Francisco

    2016-01-01

    This case report aimed to highlight the usefulness of cone beam computed tomography (CBCT) and its post-processing tools for the diagnosis, follow-up and treatment planning of invasive cervical resorption (ICR). A 16-year-old female patient was referred for periapical radiographic examination, which revealed an irregular but well demarcated radiolucency in the mandibular right central incisor. In addition, CBCT scanning was performed to distinguish between ICR and internal root resorption. After the diagnosis of ICR, the patient was advised to return shortly but did so only six years later. At that time, another CBCT scan was performed and CBCT registration and subtraction were done to document lesion progress. These imaging tools were able to show lesion progress and extent clearly and were fundamental for differential diagnosis and treatment decision. PMID:27652714

  7. Bone resorption by isolated human osteoclasts in vitro: effects of calcitonin.

    PubMed

    Murrills, R J; Shane, E; Lindsay, R; Dempster, D W

    1989-04-01

    Human osteoclasts were isolated from 12- to 17-week-old fetal tissue and from transiliac crest bone biopsies for an in vitro study of their biology. A hypodermic needle was used to flush either the fetal long bones or the trabeculae of the iliac crest bone biopsy with tissue culture medium and the resulting cell suspension sedimented briefly either onto the surface of plastic tissue culture dishes, for time-lapse microcinematography, or onto slices of devitalized bovine cortical bone for quantitative assay of bone resorption. The osteoclasts were motile, tartrate-resistant acid phosphatase positive and capable of excavating pits in slices of devitalized bovine cortical bone. Human calcitonin, at doses of 1 ng/ml and 1 microgram/ml, caused a 70% inhibition of bone resorption by human fetal osteoclasts over a 24 h period but had no apparent effect on the morphology or motility of either fetal or adult osteoclasts. PMID:2728929

  8. Study on bone resorption behavior of osteoclast under drug effect using 41Ca tracing

    NASA Astrophysics Data System (ADS)

    Kejun, Dong; Liyan, Lu; Ming, He; Yinggen, Ouyang; Yan, Xue; Chaoli, Li; Shaoyong, Wu; Xianggao, Wang; Hongtao, Shen; Jianjun, Gao; Wei, Wang; Dafu, Chen; Yonggang, Xing; Jian, Yuan; Shan, Jiang

    2013-01-01

    The mechanisms governing calcium fluxes during bone remodeling processes in Osteoporosis (OP) patients are poorly known. Understanding the changes of Osteoclasts (OC) during this dynamic transition is important to prevent and cure OP. The exploration of long-lived 41Ca (T1/2 = 1.04 × 105 years) tracer combined with AMS measurements leads to the possibility of monitoring the bone resorption behavior of OC in OP patients. In this work, the behavior of OC with the administration of Strontium Ranelate (SR), a drug for OP, was studied by using 41Ca labeled hydroxyapatite (HAP) to simulate the bone. AMS on the HI-13 tandem accelerator at CIAE was used to determine trace amounts of 41Ca. The results show that the technique of 41Ca tracing with AMS can be used to quantitatively monitor the behavior of OC in bone resorption under the effects of drugs. Experimental details and preliminary results will be presented.

  9. Management of external invasive cervical resorption of tooth with Biodentine: A case report

    PubMed Central

    Baranwal, Akash Kumar

    2016-01-01

    Invasive cervical resorption (ICR) of a tooth is relatively uncommon and the etiology is not very clear. It is sometimes misdiagnosed and can lead to improper management or tooth loss. Correct diagnosis and proper management can result in a successful outcome. The treatment should aim toward the complete suppression of all resorbing tissues and the reconstruction of resorptive defect by the placement of a suitable filling material or some biological systems. One of the most significant developments of the past decade, i.e. the operating microscope used for surgical endodontics, helps the surgeon to assess pathological changes more precisely and to remove pathological lesions with far greater precision, thus minimizing tissue damage. The aim of this article was to show the management of maxillary left central incisor diagnosed with external ICR using Biodentine under dental operatory microscope (DOM). PMID:27217649

  10. Management of external invasive cervical resorption of tooth with Biodentine: A case report.

    PubMed

    Baranwal, Akash Kumar

    2016-01-01

    Invasive cervical resorption (ICR) of a tooth is relatively uncommon and the etiology is not very clear. It is sometimes misdiagnosed and can lead to improper management or tooth loss. Correct diagnosis and proper management can result in a successful outcome. The treatment should aim toward the complete suppression of all resorbing tissues and the reconstruction of resorptive defect by the placement of a suitable filling material or some biological systems. One of the most significant developments of the past decade, i.e. the operating microscope used for surgical endodontics, helps the surgeon to assess pathological changes more precisely and to remove pathological lesions with far greater precision, thus minimizing tissue damage. The aim of this article was to show the management of maxillary left central incisor diagnosed with external ICR using Biodentine under dental operatory microscope (DOM).

  11. Condylar resorption after orthognathic surgery. Evaluation of treatment in 8 patients.

    PubMed

    Merkx, M A; Van Damme, P A

    1994-02-01

    Several articles have been published on the subject of condylar resorption as a complication of orthognathic surgery. However, since there is little reference to treatment, the frequency of this phenomenon and the results of therapy are evaluated in a retrospective study. 8 patients out of a group of 329 who underwent sagittal split osteotomy in a 10-year period (251 bilateral, 73 Le Fort I + bilateral and 5 unilateral), were treated actively following the development of condylar resorption. 4 patients were operated upon a second time while others underwent occlusal rehabilitation. The results for the patients who underwent revisional surgery were unsatisfactory, with poor aesthetics and occlusal stability. The patients treated with an occlusal splint (+/- orthodontics and/or prosthetic therapy) had a functional occlusion and tolerable temporo-mandibular-joint complaints.

  12. Interdisciplinary Approach for Management of Iatrogenic Internal Root Resorption: A Case Report.

    PubMed

    Ramazani, Mohsen; Asgary, Saeed; Zarenejad, Nafiseh; Mehrani, Javad

    2016-01-01

    For management of a symptomatic maxillary lateral incisor with dull pain on chewing, suppurative sinus tract, defective metal-ceramic crown and iatrogenic internal root resorption, an interdisciplinary approach was taken. Two-visit nonsurgical treatment with calcium-enriched mixture (CEM) cement, replacement of metal-ceramic crown with all-ceramic crown and corrective periodontal plastic surgery were included in the treatment plan. Six-month and one-year follow-ups revealed complete resolution of signs and symptoms and radiographic healing. This case report highlights the importance of adequate cooling during crown preparation to preserve the pulp vitality and prevent internal resorptive lesions and also the profound sealing ability and biocompatibility of CEM cement. PMID:26843882

  13. Mapping nutrient resorption efficiencies of subarctic cryptogams and seed plants onto the Tree of Life

    PubMed Central

    Lang, Simone I; Aerts, Rien; van Logtestijn, Richard S P; Schweikert, Wenka; Klahn, Thorsten; Quested, Helen M; van Hal, Jurgen R; Cornelissen, Johannes H C

    2014-01-01

    Nutrient resorption from senescing photosynthetic organs is a powerful mechanism for conserving nitrogen (N) and phosphorus (P) in infertile environments. Evolution has resulted in enhanced differentiation of conducting tissues to facilitate transport of photosynthate to other plant parts, ultimately leading to phloem. Such tissues may also serve to translocate N and P to other plant parts upon their senescence. Therefore, we hypothesize that nutrient resorption efficiency (RE, % of nutrient pool exported) should correspond with the degree of specialization of these conducting tissues across the autotrophic branches of the Tree of Life. To test this hypothesis, we had to compare members of different plant clades and lichens within a climatic region, to minimize confounding effects of climatic drivers on nutrient resorption. Thus, we compared RE among wide-ranging basal clades from the principally N-limited subarctic region, employing a novel method to correct for mass loss during senescence. Even with the limited numbers of species available for certain clades in this region, we found some consistent patterns. Mosses, lichens, and lycophytes generally showed low REN (<20%), liverworts and conifers intermediate (40%) and monilophytes, eudicots, and monocots high (>70%). REP appeared higher in eudicots and liverworts than in mosses. Within mosses, taxa with more efficient conductance also showed higher REN. The differences in REN among clades broadly matched the degree of specialization of conducting tissues. This novel mapping of a physiological process onto the Tree of Life broadly supports the idea that the evolution of conducting tissues toward specialized phloem has aided land plants to optimize their internal nitrogen recycling. The generality of evolutionary lines in conducting tissues and nutrient resorption efficiency needs to be tested across different floras in different climatic regions with different levels of N versus P availability. PMID:25360262

  14. Pre-Eruptive Intracoronal Resorption (PEIR): Literature Review and Case Report.

    PubMed

    Omar, Samah; Choi, Jessica; Nelson, Bonnie; Shin, Michelle; Chen, Jung-Wei

    2015-05-01

    Pre-eruptive intracoronal resorption (PEIR) are lesions that are often located in the occlusal portion of the crown in unerupted teeth. The etiology and pathology of these lesions remain unclear and most go undetected until later stages of development. Prognosis is dependent on early detection, and conservative treatment is recommended. This report reviews the etiology, prevalence, diagnosis and treatment of PEIR and describes a case of a permanent second molar with PEIR diagnosed in an 11-year-old patient. PMID:26798901

  15. Morphologic criteria for root canal treatment of primary molars undergoing resorption.

    PubMed

    Rimondini, L; Baroni, C

    1995-06-01

    The endodontic anatomy of primary molars is difficult to predict because of the balance of resorption and hard tissue deposition. In particular, the resorption causes perforating lacunae across the wall of the root, even at the furcation level, and modifies shape, dimension and position of endodontic apex. The phenomenon can be so deep as to compromise endodontic therapy. The first aim of the study was to verify if reliable criteria can be found for treatability in primary molars undergoing resorption, i.e. if it is possible to predict if perforating lacunae are present or not. The second aim of the study was to verify if other informations needed for endodontic treatment, as shape, dimension and location of the apex, and curvature of the root canal can be predicted. For the study, 80 extracted primary molars, 75 of which pulpally involved by caries, were selected. The treatability was evaluated in term of root length, root shape, dimension and shape of endodontic apex, age of the patient and X-ray index of resorption. The association between variables was performed by multiple correspondence analysis. The results suggested that root length was the most reliable criterion of the integrity of the root. The borderline of treatability was at the length of 4 mm. The position of endodontic apex related to anatomical apex, and the lingual related to the buccal root length were analyzed by linear regression analysis. The canal length was often similar to the root length (i.e. the endo and anatomical apices were very close) in lower and upper molars. However, in lower molars, if two or more canals were present in the same root, a discrepancy was observed between buccal and lingual root length. This finding was constant in first lower molars. In addition regression analysis provided a linear function between the lengths of the buccal and lingual side of the same root in lower molars. Its coefficient b was 0.73. PMID:7641630

  16. Effect of Nanocrystalline Hydroxyapatite Socket Preservation on Orthodontically Induced Inflammatory Root Resorption

    PubMed Central

    Seifi, Massoud; Arayesh, Ali; Shamloo, Nafise; Hamedi, Roya

    2015-01-01

    Objective Orthodontically induced inflammatory root resorption (OIIRR) is considered to be an important sequel associated with orthodontic tooth movement (OTM). OTM after Socket preservation enhances the periodontal condition before orthodontic space closure. The purpose of this study is to investigate the histologic effects of NanoBone®, a new highly nonsintered porous nano-crystalline hydroxyapatite bone on root resorption following OTM. Materials and Methods This experimental study was conducted on four male dogs. In each dog, four defects were created at the mesial aspects of the maxillary and mandibular first premolars. The defects were filled with NanoBone®. We used the NiTi closed coil for mesial movement of the first premolar tooth. When the experimental teeth moved approximately halfway into the defects, after two months, the animals were sacrificed and we harvested the area of interest. The first premolar root and adjacent tissues were histologically evaluated. The three-way ANOVA statistical test was used for comparison. Results The mean root resorption in the synthetic bone substitute group was 22.87 ± 11.25×10-4mm2 in the maxilla and 21.41 ± 11.25×10-4mm2 in the mandible. Statistically, there was no significant difference compared to the control group (p>0.05). Conclusion The use of a substitution graft in the nano particle has some positive effects in accessing healthy periodontal tissue following orthodontic procedures without significant influence on root resorption (RR). Histological evaluation in the present study showed osteoblastic activity and remodeling environment of nanoparticles in NanoBone®. PMID:25685742

  17. Mapping nutrient resorption efficiencies of subarctic cryptogams and seed plants onto the Tree of Life.

    PubMed

    Lang, Simone I; Aerts, Rien; van Logtestijn, Richard S P; Schweikert, Wenka; Klahn, Thorsten; Quested, Helen M; van Hal, Jurgen R; Cornelissen, Johannes H C

    2014-06-01

    Nutrient resorption from senescing photosynthetic organs is a powerful mechanism for conserving nitrogen (N) and phosphorus (P) in infertile environments. Evolution has resulted in enhanced differentiation of conducting tissues to facilitate transport of photosynthate to other plant parts, ultimately leading to phloem. Such tissues may also serve to translocate N and P to other plant parts upon their senescence. Therefore, we hypothesize that nutrient resorption efficiency (RE, % of nutrient pool exported) should correspond with the degree of specialization of these conducting tissues across the autotrophic branches of the Tree of Life. To test this hypothesis, we had to compare members of different plant clades and lichens within a climatic region, to minimize confounding effects of climatic drivers on nutrient resorption. Thus, we compared RE among wide-ranging basal clades from the principally N-limited subarctic region, employing a novel method to correct for mass loss during senescence. Even with the limited numbers of species available for certain clades in this region, we found some consistent patterns. Mosses, lichens, and lycophytes generally showed low REN (<20%), liverworts and conifers intermediate (40%) and monilophytes, eudicots, and monocots high (>70%). REP appeared higher in eudicots and liverworts than in mosses. Within mosses, taxa with more efficient conductance also showed higher REN. The differences in REN among clades broadly matched the degree of specialization of conducting tissues. This novel mapping of a physiological process onto the Tree of Life broadly supports the idea that the evolution of conducting tissues toward specialized phloem has aided land plants to optimize their internal nitrogen recycling. The generality of evolutionary lines in conducting tissues and nutrient resorption efficiency needs to be tested across different floras in different climatic regions with different levels of N versus P availability. PMID:25360262

  18. Gallium a unique anti-resorptive agent in bone: Preclinical studies on its mechanisms of action

    SciTech Connect

    Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R. ); Jones, K.W. )

    1990-01-01

    The discovery of gallium as a new and unique agent for the treatment of metabolic bone disorders was in part fortuitous. Gallium is an exciting new therapeutic agent for the treatment of pathologic states characterized by accelerated bone resorption. Compared to other therapeutic metal compounds containing platinum or germanium, gallium affects its antiresorptive action without any evidence of a cytotoxic effect on bone cells. Gallium is unique amongst all therapeutically available antiresorptive agents in that it favors bone formation. 18 refs., 1 fig.

  19. Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone.

    PubMed

    Asou, Y; Rittling, S R; Yoshitake, H; Tsuji, K; Shinomiya, K; Nifuji, A; Denhardt, D T; Noda, M

    2001-03-01

    Osteoclastic bone resorption requires a number of complex steps that are under the control of local regulatory molecules. Osteopontin is expressed in osteoclasts and is also present in bone matrix; however, its biological function has not been fully understood. To elucidate the role of osteopontin in the process of osteoclastic bone resorption, we conducted ectopic bone implantation experiments using wild-type and osteopontin knockout mouse. In the wild-type group, bone discs from calvariae implanted ectopically in muscle were resorbed, and their mass was reduced by 25% within 4 weeks. In contrast, the mass of the bone discs from calvariae of osteopontin knockout mice was reduced by only 5% when implanted in osteopontin knockout mice. Histological analyses indicated that the number of osteoclasts associated with the implanted bones was reduced in the osteopontin knockout mice. As osteopontin deficiency does not suppress osteoclastogenesis per se, we further examined vascularization immunohistologically and found that the number of vessels containing CD31-positive endothelial cells around the bone discs implanted in muscle was reduced in the osteopontin knockout mice. Furthermore, sc implantation assays indicated that the length and branching points of the newly formed vasculatures associated with the bone discs were also reduced in the absence of osteopontin. In this assay, tartrate-resistant acid phosphatase-positive area of the bone discs was also reduced in the osteopontin knockout mice, indicating further the link between the osteopontin-dependent vascularization and osteoclast accumulation. The bone resorption defect could be rescued by topical administration of recombinant osteopontin to the bones implanted in muscle. These observations indicate that osteopontin is required for efficient vascularization by the hemangiogenic endothelial cells and subsequent osteoclastic resorption of bones. PMID:11181551

  20. Effect of odanacatib on root resorption and alveolar bone metabolism during orthodontic tooth movement.

    PubMed

    Wei, X X; Chu, J P; Zou, Y Z; Ru, N; Cui, S X; Bai, Y X

    2015-01-01

    The aim of this study was to investigate the effect of local administration of odanacatib (ODN) on orthodontic root resorption and the status of alveolar bone metabolism in rat molars. All specimens were scanned using microcomputed tomography and then the raw images were reconstructed. The total volume of the root resorption craters of the 60 g-NS (normal saline) group was higher than in the 60 g-ODN group and the control group. In the 60 g-NS group, the bone volume fraction values of alveolar bone were significantly decreased compared with the other 2 groups. There were no significant differences in the bone volume fraction values of the tibiae among the 3 groups. The results of tartrate-resistant acid phosphatase-positive (TRAP+) numbers showed that there was no difference between the 60 g-NS group and the 60 g-ODN group. The expression of cathepsin K was decreased significantly in the 60 g-ODN group. These results indicate that ODN reduces orthodontics-induced external root resorption and increases alveolar bone metabolism. This may be because ODN inhibits the activity of odontoclasts, but maintains the quantity of odontoclasts and enhances bone formation. ODN promotes local alveolar bone metabolism, but does not affect systemic bone metabolism. PMID:26782444

  1. Effect of low-intensity pulsed ultrasound on orthodontically induced root resorption in beagle dogs.

    PubMed

    Al-Daghreer, Saleh; Doschak, Michael; Sloan, Alastair J; Major, Paul W; Heo, Giseon; Scurtescu, Cristian; Tsui, Ying Y; El-Bialy, Tarek

    2014-06-01

    We investigated the effect of low-intensity pulsed ultrasound (LIPUS) on orthodontically induced inflammatory root resorption in vivo. Ten beagle dogs were treated with an orthodontic appliance to move the mandibular fourth premolars bodily. The orthodontic movement was carried out for 4 wk with a continuous force of 1 N/side; using a split-mouth model, LIPUS was applied daily for 20 min. Fourth premolar and surrounding periodontal tissue were evaluated with micro-computed tomography and hematoxylin and eosin and tartrate-resistant acid phosphatase staining. We calculated the number, volume and distribution of root resorption lacunae and their percentage relative to total root volume, orthodontic tooth movement and periodontal ligament space. There was no significant difference in orthodontic tooth movement between the two sides. LIPUS significantly reduced the number of orthodontically induced inflammatory root resorption initiation areas by 71%, reduced their total volume by 68% and reduced their volume relative to the affected root total volume by 70%. LIPUS induced the formation of a precementum layer, thicker cementum and reparative cellular cementum.

  2. Three-dimensional localization of impacted canines and root resorption assessment using cone beam computed tomography.

    PubMed

    Almuhtaseb, Eyad; Mao, Jing; Mahony, Derek; Bader, Rawan; Zhang, Zhi-xing

    2014-06-01

    The purpose of this study was to develop a new way to localize the impacted canines from three dimensions and to investigate the root resorption of the adjacent teeth by using cone beam computed tomography (CBCT). Forty-six patients undergoing orthodontic treatments and having impacted canines in Tongji Hospital were examined. The images of CBCT scans were obtained from KaVo 3D exam vision. Angular and linear measurements of the cusp tip and root apex according to the three planes (mid-sagittal, occlusal and frontal) have been taken using the cephalometric tool of the InVivo Dental Anatomage Version 5.1.10. The measurements of the angular and linear coordinates of the maxillary and mandibular canines were obtained. Using this technique the operators could envision the location of the impacted canine according to the three clinical planes. Adjacent teeth root resorption of 28.26 % was in the upper lateral incisors while 17.39% in upper central incisors, but no lower root resorption was found in our samples. Accurate and reliable localization of the impacted canines could be obtained from the novel analysis system, which offers a better surgical and orthodontic treatment for the patients with impacted canines.

  3. Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

    PubMed Central

    van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

    2000-01-01

    Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. PMID:10869429

  4. Effect of odanacatib on root resorption and alveolar bone metabolism during orthodontic tooth movement.

    PubMed

    Wei, X X; Chu, J P; Zou, Y Z; Ru, N; Cui, S X; Bai, Y X

    2015-12-22

    The aim of this study was to investigate the effect of local administration of odanacatib (ODN) on orthodontic root resorption and the status of alveolar bone metabolism in rat molars. All specimens were scanned using microcomputed tomography and then the raw images were reconstructed. The total volume of the root resorption craters of the 60 g-NS (normal saline) group was higher than in the 60 g-ODN group and the control group. In the 60 g-NS group, the bone volume fraction values of alveolar bone were significantly decreased compared with the other 2 groups. There were no significant differences in the bone volume fraction values of the tibiae among the 3 groups. The results of tartrate-resistant acid phosphatase-positive (TRAP+) numbers showed that there was no difference between the 60 g-NS group and the 60 g-ODN group. The expression of cathepsin K was decreased significantly in the 60 g-ODN group. These results indicate that ODN reduces orthodontics-induced external root resorption and increases alveolar bone metabolism. This may be because ODN inhibits the activity of odontoclasts, but maintains the quantity of odontoclasts and enhances bone formation. ODN promotes local alveolar bone metabolism, but does not affect systemic bone metabolism.

  5. The influence of age on adaptive bone formation and bone resorption.

    PubMed

    Birkhold, Annette I; Razi, Hajar; Duda, Georg N; Weinkamer, Richard; Checa, Sara; Willie, Bettina M

    2014-11-01

    Bone is a tissue with enormous adaptive capacity, balancing resorption and formation processes. It is known that mechanical loading shifts this balance towards an increased formation, leading to enhanced bone mass and mechanical performance. What is not known is how this adaptive response to mechanical loading changes with age. Using dynamic micro-tomography, we show that structural adaptive changes of trabecular bone within the tibia of living mice subjected to two weeks of in vivo cyclic loading are altered by aging. Comparisons of 10, 26 and 78 weeks old animals reveal that the adaptive capacity diminishes. Strikingly, adaptation was asymmetric in that loading increases formation more than it reduces resorption. This asymmetry further shifts the (re)modeling balance towards a net bone loss with age. Loading results in a major increase in the surface area of mineralizing bone. Interestingly, the resorption thickness is independent of loading in trabecular bone in all age groups. This data suggests that during youth, mechanical stimulation induces the recruitment of bone modeling cells whereas in old age, only bone forming cells are affected. These findings provide mechanistic insights into the processes that guide skeletal aging in mice as well as in other mammals.

  6. Root resorption of upper permanent incisor caused by impacted canine. An analysis of 23 cases.

    PubMed

    Sasakura, H; Yoshida, T; Murayama, S; Hanada, K; Nakajima, T

    1984-08-01

    Unusual root resorption of 12 central and 11 lateral upper permanent incisors in 11 patients is described. The degree of resorption ranged from loss of the apical 1/4 to almost complete loss of root structure. Excepting 1 case, permanent canines were partially or completely impacted and their crowns were in close apposition to the resorbed surfaces of the incisors. The roots of the canines were either in the process of formation or completely formed. The findings suggest that the pressure from the canine which persists in moving downward despite the lack of space to permit normal eruption could cause root resorption of adjacent incisors even in the absence of systemic factors. Of 14 extracted incisors, 10 were replaced orthodontically by the impacted canines, whereas the spaces of the extracted incisors were restored by prosthetic means in the 4 other cases. 6 incisors were preserved without any treatment and 2 with the aid of a sapphire dento-osseous anchor pin. Since the resorbed incisors were mostly free of pain, early detection by radiographic examination is essential to establish a proper diagnosis.

  7. Time course of "escape" from calcitonin-induced inhibition of motility and resorption of disaggregated osteoclasts.

    PubMed

    Kanehisa, J

    1989-01-01

    The reversible calcitonin (CT)-induced inhibition of osteoclastic activity has been studied to clarify the mechanisms responsible for the so-called "escape phenomenon." Osteoclasts disaggregated from neonatal rabbits were cultured on glass coverslips or thin bovine bone slices. Resorption activity was evaluated by using time-lapse recording and scanning electron microscopy. Addition of CT to the cultures caused most osteoclasts on glass surfaces to be immotile and contracted. From 1.5 h onward, in cultures with CT, osteoclasts started to escape from CT-induced quiescence independently of other cells. CT also prevented osteoclasts on bone slices from excavating bone while concomitant cell immobility occurred. Inhibited osteoclasts were able to regain apparent bone-resorbing potency only after resumption of cytoplasmic immobility. The resumption of bone resorption could begin as early as 9.7 h after CT addition. The observations indicate that CT-induced inhibition of osteoclastic bone resorption is associated with inhibition of cytoplasmic motility and that the "escape" phenomenon reflects resumption of activity of osteoclasts that were previously inhibited by CT action rather than the resportive activity of newly formed osteoclasts. PMID:2765310

  8. Histomorphometric evidence for echistatin inhibition of bone resorption in mice with secondary hyperparathyroidism.

    PubMed

    Masarachia, P; Yamamoto, M; Leu, C T; Rodan, G; Duong, L

    1998-03-01

    Echistatin, an RGD-containing peptide, was shown to inhibit the acute calcemic response to exogenous PTH or PTH-related protein (PTH-rP) in thyroparathyroidectomized rats, suggesting that echistatin inhibits bone resorption. In this study: 1) we present histological evidence for echistatin inhibition of bone resorption in mice with secondary hyperparathyroidism, and show that 2) echistatin binds to osteoclasts in vivo, 3) increases osteoclast number, and 4) does not detectably alter osteoclast morphology. Infusion of echistatin (30 microg/kg x min) for 3 days prevented the 2.6-fold increase in tibial cancellous bone turnover and the 36% loss in bone volume, produced by a low calcium diet. At the light microscopy level, echistatin immunolocalized to osteoclasts and megakaryocytes. Echistatin treatment increased osteoclast-covered bone surface by about 50%. At the ultrastructural level, these osteoclasts appeared normal, and the fraction of cells containing ruffled borders and clear zones was similar to controls. Echistatin was found on the basolateral membrane and in intracellular vesicles of actively resorbing osteoclasts. Weak labeling was found in the ruffled border, and no immunoreactivity was detected at the clear zone/bone surface interface. These findings provide histological evidence for echistatin binding to osteoclasts and for inhibition of bone resorption in vivo, through reduced osteoclast efficacy, without apparent changes in osteoclast morphology.

  9. Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.; Morey-Holton, E. R.; Doty, S. B.; Currier, P. A.; Tanner, S. J.; Halloran, B. P.

    1994-01-01

    Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

  10. Family 2 cystatins inhibit osteoclast-mediated bone resorption in calvarial bone explants.

    PubMed

    Brand, H S; Lerner, U H; Grubb, A; Beertsen, W; Nieuw Amerongen, A V; Everts, V

    2004-09-01

    Osteoclastic bone resorption depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteine proteinases. Biochemical studies have shown that cystatins, naturally occurring inhibitors of these enzymes, inhibit bone matrix degradation. Since the mechanism by which cystatins exert this inhibitory effect is not completely resolved yet, we studied the effect of cystatins on bone resorption microscopically and by Ca-release measurements. Calvarial bone explants were cultured in the presence or absence of family 2 cystatins and processed for light and electron microscopic analysis, and the culture media were analyzed for calcium release. Both egg white cystatin and human cystatin C decreased calcium release into the medium significantly. Microscopic analyses of the bone explants demonstrated that in the presence of either inhibitor, a high percentage of osteoclasts was associated with demineralized non-degraded bone matrix. Following a 24-h incubation in the presence of cystatin C, 41% of the cells were adjacent to areas of demineralized non-degraded bone matrix, whereas in controls, this was only 6%. If bone explants were cultured with both PTH and cystatin C, 60% of the osteoclasts were associated with demineralized non-degraded bone matrix, compared to 27% for bones treated with PTH only (P < 0.01). Our study provides evidence that cystatins, the naturally occurring inhibitors of cysteine proteinases, reversibly inhibit bone matrix degradation in the resorption lacunae adjacent to osteoclasts. These findings suggest the involvement of cystatins in the modulation of osteoclastic bone degradation.

  11. Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

    SciTech Connect

    Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

    2014-01-10

    Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

  12. Dental Management of a Patient with Multiple Idiopathic Cervical Root Resorption.

    PubMed

    Ali, Rahat; Fayle, Stephen; Langley, David; Altaie, Asmaa; Nattress, Brian

    2015-09-01

    Multiple Idiopathic Cervical Root Resorption (MICRR) is a rare condition. It initiates at the cemento-enamel junction of multiple teeth. The lesions continue to grow until they unite, thereby undermining the entire coronal structure of affected teeth. Its distribution can vary from a single region to the entire dentition and the number of teeth affected by resorption tends to increase as the condition is followed over time. The teeth themselves appear clinically normal. The aetiology of MICRR is unknown and it is considered to be a diagnosis of exclusion. The condition tends to be progressive. Consequently, root treatments/surgical curettage and restoration of the lesions have been unsuccessful at arresting the condition. Affected teeth are often extracted in anticipation of catastrophic fracture and have been replaced with partial or complete dentures. In this case report, we describe how a young female patient was dentally managed over 10 years and ultimately rehabilitated with dental implants. CPD/CLINICAL RELEVANCE: Patients suspected of having multiple idiopathic cervical root resorption may require specialist, multidisciplinary care and require referral to an appropriate secondary care unit for treatment planning and potential oral rehabilitation. PMID:26630864

  13. A histopathological study of the role of periodontal ligament tissue in root resorption in the rat.

    PubMed

    Shiraishi, C; Hara, Y; Abe, Y; Ukai, T; Kato, I

    2001-02-01

    Whether periodontal ligament (PDL) tissue is capable of inducing root resorption was examined. The distal root of the rat molar was sectioned at the furcation and the PDL tissue removed from the root (non-PDL group, n=40). The distal root with the PDL intact was also prepared (PDL-intact group, n=40). The roots were transplanted into the dorsal skin of the rat. On the 1st, 3rd, 5th, 7th, 10th, 14th, 21st or 28th day after transplantation, the roots were removed together with surrounding dorsal subcutaneous tissue and were fixed, demineralized and embedded in paraffin. Serial sections from each block were stained with haematoxylin and eosin or by the tartrate-resistant acid phosphatase (TRAP) method to observe root-resorbing cell formation. Cyclo-oxygenase-2 (COX2) was also detected immunohistologically to examine prostaglandin E(2) production. On the 7th day after transplantation, multinucleated root-resorbing cells with TRAP were observed in the PDL-intact group. The number of TRAP-positive cells peaked on the 10th day after transplantation. COX2-positive cells were observed in PDL during the early experimental stages. No root resorption was seen in the non-PDL group. These results suggest that PDL tissue is involved in the formation of root-resorbing cells and root resorption. PMID:11163317

  14. Is the fasting calcium/creatinine a bone resorption marker in patients with calcium renal stones?

    PubMed

    Arrabal-Polo, Miguel Angel; Arrabal-Martin, Miguel; Poyatos-Andujar, Antonio; Cardenas-Grande, Encarnacion; Merino-Salas, Sergio; Zuluaga-Gomez, Armando

    2012-06-01

    Osteoporosis and osteopenia are an important endocrine-metabolic disease that affect women and men from a certain age and it has a high risk and health cost. The aim of this short communication is to show that fasting calcium/creatinine ratio in patients with calcium stones is a marker of bone resorption.We studied 180 patients with renal stones with calcium composition and the relationship of them between the calcium/creatinine in urine after 8 h of fasting with bone densitometry (T-score) and values of bone resorption marker β-crosslaps (ng/ml). The Pearson correlation test was applied for the analysis of linear correlations between quantitative variables.We have observed a statistically significant positive linear correlation between the fasting calcium/creatinine and serum and β-crosslaps (R = 0.534, p < 0.0001) and a statistically significant negative linear correlation between fasting calcium/creatinine and T-score of bone densitometry in hip (R = -0.237, p = 0.002), femoral neck (R = -0.217, p = 0.009) and lumbar spine (R = 0.292, p = 0.001).The fasting ratio calcium/creatinine in urine is associated with increased levels of β-crosslaps marker and therefore may be useful as a marker of bone resorption in these patients.

  15. siRNA Knock-Down of RANK Signaling to Control Osteoclast-Mediated Bone Resorption

    PubMed Central

    Wang, Yuwei; Grainger, David W.

    2010-01-01

    Purpose To demonstrate the ability of small interfering (si)RNA targeting the cell receptor, RANK, to control osteoclast function in cultures of both primary and secondary osteoclasts and their precursor cells. Methods siRNA targeting RANK was transfected into both RAW264.7 and primary bone marrow cell cultures. RANK knock-down by siRNA and functional inhibition were assessed in both mature osteoclast and their precursor cell cultures. RANK mRNA message and protein expression after the transfections were analyzed by PCR and Western blot, respectively. Off-target effects were assessed. The inhibition of osteoclast formation was evaluated using tartrate-resistant acid phosphatase (TRAP) assay, and subsequent bone resorption was determined by resorption pit assay. Results Both osteoclasts and osteoclast precursors can be targeted by siRNA in serum-containing media. Delivery of siRNA targeting RANK to both RAW 264.7 and primary bone marrow cell cultures produces short term repression of RANK expression without off-targeting effects, and significantly inhibits both osteoclast formation and bone resorption. Moreover, data support successful RANK knock-down by siRNA specifically in mature osteoclast cultures. Conclusions RANK is demonstrated to be an attractive target for siRNA control of osteoclast activity, with utility for development of new therapeutics for low bone mass pathologies or osteoporosis. PMID:20333451

  16. Epstein-Barr virus infection induces bone resorption in apical periodontitis via increased production of reactive oxygen species.

    PubMed

    Jakovljevic, Aleksandar; Andric, Miroslav; Miletic, Maja; Beljic-Ivanovic, Katarina; Knezevic, Aleksandra; Mojsilovic, Slavko; Milasin, Jelena

    2016-09-01

    Chronic inflammatory processes in periapical tissues caused by etiological agents of endodontic origin lead to apical periodontitis. Apart from bacteria, two herpesviruses, Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) are recognized as putative pathogens in apical periodontitis. Although previous reports suggest the involvement of EBV in the pathogenesis of apical periodontitis, its exact role in periapical bone resorption has not yet been fully elucidated. We hypothesize that EBV infection in apical periodontitis is capable of inducing periapical bone resorption via stimulation of reactive oxygen species (ROS) overproduction. Increased levels of ROS induce expression of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). RANKL binding to receptor activator of nuclear factor κB (RANK) present on the surface of preosteoclasts induces their maturation and activation which consequently leads to bone resorption. The potential benefit of antiviral and antioxidant-based therapies in periapical bone resorption treatment remains to be assessed. PMID:27515196

  17. A Comparison of pical Root Resorption in Incisors after Fixed Orthodontic Treatment with Standard Edgewise and Straight Wire (MBT) Method

    PubMed Central

    Zahed Zahedani, SM; Oshagh, M; Momeni Danaei, Sh; Roeinpeikar, SMM

    2013-01-01

    Statement of Problem: One of the major outcomes of orthodontic treatment is the apical root resorption of teeth moved during the treatment. Identifying the possible risk factors, are necessary for every orthodontist. Purpose: The aim of this study was to compare the rate of apical root resorption after fixed orthodontic treatment with standard edgewise and straight wire (MBT) method, and also to evaluate other factors effecting the rate of root resorption in orthodontic treatments. Materials and Method: In this study, parallel periapical radiographs of 127 patients imaging a total of 737 individual teeth, were collected. A total of 76 patients were treated by standard edgewise and 51 patients by straight wire method. The periapical radiographs were scanned and then the percentage of root resorption was calculated by Photoshop software. The data were analyzed by Paired-Samples t-test and the Generalized Linear Model adopting the SPSS 15.0. Results: In patients treated with straight wire method (MBT), mean root resorption was 18.26% compared to 14.82% in patients treated with standard edgewise technique (p< .05). Male patients had higher rate of root resorption,statistically significant (p< .05). Age at onset of treatment, duration of treatment, type of dental occlusion, premolar extractions and the use of intermaxillary elastics had no significant effect on the root resorption in this study. Conclusion: Having more root resorption in the straight wire method and less in the standard edgewise technique can be attributed to more root movement in pre-adjusted MBT technique due to the brackets employed in this method. PMID:24724131

  18. Macrophage functions in Biozzi mice.

    PubMed Central

    Dockrell, H M; Taverne, J; Lelchuk, R; Depledge, P; Brown, I N; Playfair, J H

    1985-01-01

    The faster degradation of antigen by macrophages in Biozzi low (L) responder mice, compared to Biozzi high (H) responder mice, is thought to be responsible for their lower antibody response. We have measured four functions associated with macrophages to see whether macrophages from L mice were generally more active than those from H mice. Peritoneal macrophages obtained from normal mice were compared with those from groups of mice given Mycobacterium bovis BCG or Propionibacterium acnes. Cells from normal H mice gave a stronger oxidative burst when triggered with phorbol myristate acetate, and were more cytotoxic for tumour cells than cells from L mice. Cells from all mice injected with BCG or P. acnes gave a stronger oxidative burst, and were more cytotoxic for tumour cells; again, both responses were higher in H mice than in L mice. By contrast, when groups of mice that had received P. acnes were given endotoxin and bled, higher titres of tumour necrosis factor were found in the sera of L mice. Spleen cells from both lines of mice released similar levels of interleukin-1, both spontaneously and in response to lipopolysaccharide. Our results suggest that these various macrophage responses are expressed independently in H and L mice. PMID:3894222

  19. Calcineurin/NFAT pathway mediates wear particle-induced TNF-α release and osteoclastogenesis from mice bone marrow macrophages in vitro

    PubMed Central

    Liu, Feng-xiang; Wu, Chuan-long; Zhu, Zhen-an; Li, Mao-qiang; Mao, Yuan-qing; Liu, Ming; Wang, Xiao-qing; Yu, De-gang; Tang, Ting-ting

    2013-01-01

    Aim: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. Methods: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA. Results: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 μmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h). Conclusion: Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis. PMID:24056707

  20. Anti-Resorptive Activity of Anti-Hypertensive Agent ACEi in Older Men

    NASA Technical Reports Server (NTRS)

    Rianon, Nahid; Edwards, BeJier; Nhonthachit, Phetsamong; Messick, Amanda; Gagel, Robert; Smith, Scott M.

    2016-01-01

    Hypertension (HTN) is associated with bone loss due to activation of the renin- angiotensin system (RAS) which in turn affects bone turnover. Animal studies have shown decreased bone resorption (up to 19%) and increased bone mass (up to 2%) following treatment with RAStargeted antihypertensive medications (e.g., angiotensin converting enzyme inhibitors, ACEi). Cross-sectional human studies have documented greater femoral neck BMD in older hypertensive men and women treated with ACEi compared to those not-treated with ACEi (nor other RAS-targeted medications). These findings raise the potential for ACEi use in preventing, or at a minimum slowing bone loss due to age or even microgravity. Based on this, we conducted a cohort study to investigate if ACEi treatment would decrease bone resorption in humans. We investigated changes in serum CTX and P1NP in 10 hypertensive men (45 years or older) treated with (N=5) without (N=5) exposure to ACEi for 3-months. Lisinopril was the ACEi used, and dose was adjusted as deemed appropriate by the attending physicians. Participants did not have any known skeletal health problem and were not exposed to any bisphosphonates or hydrochlorothiazides. A small sample size prevented detailed statistical analysis and hence, we present a preliminary descriptive report of our findings. Participants' age was 57+/-7 years (mean +/-SD), baseline body mass index was 27+/-5 kg/sq m, serum concentration of 25-hydroxyvitamin D was 66+/-17 nmol/L and parathyroid hormone was 30+/-13 pg/ml. After Lisinopril treatment, men demonstrated a 10% decrease in the bone resorption marker C-terminal telopeptide (CTX) and 5% decrease in formation marker procollagen type 1 amino-terminal pro-peptide (P1NP). On the contrary, serum CTX increased 41% and P1NP increased 10% in those who were not treated with ACEi. This is the first human study to report reduction in bone resorptive activity following ACEi treatment for hypertension in older men. Our results indicates

  1. In-vivo effect of andrographolide on alveolar bone resorption induced by Porphyromonas gingivalis and its relation with antioxidant enzymes.

    PubMed

    Al Batran, Rami; Al-Bayaty, Fouad H; Al-Obaidi, Mazen M Jamil

    2013-01-01

    Alveolar bone resorption is one of the most important facts in denture construction. Porphyromonas gingivalis (Pg) causes alveolar bone resorption, and morphologic measurements are the most frequent methods to identify bone resorption in periodontal studies. This study has aimed at evaluating the effect of Andrographolide (AND) on alveolar bone resorption in rats induced by Pg. 24 healthy male Sprague Dawley rats were divided into four groups as follows: normal control group and three experimental groups challenged orally with Pg ATCC 33277 five times a week supplemented with 20 mg/kg and 10 mg/kg of AND for twelve weeks. Alveolar bones of the left and right sides of the mandible were assessed by a morphometric method. The bone level, that is, the distance from the alveolar bone crest to cementumenamel junction (CEJ), was measured using 6.1 : 1 zoom stereomicroscope and software. AND reduced the effect of Pg on alveolar bone resorption and decreased the serum levels of Hexanoyl-Lysine (HEL); furthermore the reduced glutathione/oxidised glutathione (GSH/GSSG) ratio in AND treated groups (10 and 20 mg/kg) significantly increased when compared with the Pg group (P < 0.05). We can conclude that AND suppresses alveolar bone resorption caused by Pg in rats.

  2. Role of carbonic anhydrase in bone resorption induced by 1,25 dihydroxyvitamin D3 in vitro

    NASA Technical Reports Server (NTRS)

    Hall, G. E.; Kenny, A. D.

    1985-01-01

    The calvaria of 5-to-6-day-old mice treated with 1 x 10 to the -8th M of 1,25(OH)2D3 in vitro for 48 hours are examined in order to study the function of carbonic anhydrase in bone resorption. Calcium concentrations in the culture were measured to assess bone resorption. It is observed that 1,25(OH)2D3 effectively stimulates bone resorption in vitro and the resorption is dose-dependent. The effects of azetazolamide on 1,25(OH)2D3-induced bone resorption are investigated. The data reveal that 1,25(OH)2D3-induced calcium release is associated with an increase in the carbonic anhydrase activity of bone, and bone alkaline phosphatase activity is decreased and acid phosphatase activity is increased in response to 1,25(OH)2D3. A two-fold mechanism for 1,25(OH)2D3-induced bone resorption is proposed; the first mechanism is an indirect activation of osteoclasts and the second involves an interaction between hormone and osteoclast precursors.

  3. Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops.

    PubMed

    Li, Jing; Zeng, Li; Xie, Juan; Yue, Zhiying; Deng, Huayun; Ma, Xueyun; Zheng, Chunbing; Wu, Xiushan; Luo, Jian; Liu, Mingyao

    2015-01-01

    Excessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems. In mouse and human, XN inhibited osteoclast differentiation and osteoclast formation at the early stage. Furthermore, XN inhibited osteoclast actin-ring formation and bone resorption in a dose-dependent manner. In ovariectomized-induced bone loss mouse model and RANKL-injection-induced bone resorption model, we found that administration of XN markedly inhibited bone loss and resorption by suppressing osteoclast activity. At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca(2+)/NFATc1 signaling pathway during osteoclastogenesis. As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr. Therefore, our data demonstrated that XN inhibits osteoclastogenesis and bone resorption through RANK/TRAF6 signaling pathways. XN could be a promising drug candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis. PMID:26620037

  4. Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption.

    PubMed Central

    Greenfield, E M; Shaw, S M; Gornik, S A; Banks, M A

    1995-01-01

    Parathyroid hormone and other bone resorptive agents function, at least in part, by inducing osteoblasts to secrete cytokines that stimulate both differentiation and resorptive activity of osteoclasts. We previously identified two potentially important cytokines by demonstrating that parathyroid hormone induces expression by osteoblasts of IL-6 and leukemia inhibitory factor without affecting levels of 14 other cytokines. Although parathyroid hormone activates multiple signal transduction pathways, induction of IL-6 and leukemia inhibitory factor is dependent on activation of adenyl cyclase. This study demonstrates that adenyl cyclase is also required for stimulation of osteoclast activity in cultures containing osteoclasts from rat long bones and UMR106-01 rat osteoblast-like osteosarcoma cells. Since the stimulation by parathyroid hormone of both cytokine production and bone resorption depends on the same signal transduction pathway, we hypothesized that IL-6 might be a downstream effector of parathyroid hormone. We found that addition of exogenous IL-6 mimics the ability of parathyroid hormone to stimulate bone resorption. More importantly, an antibody directed against the IL-6 receptor blocks moderate stimulation of osteoclast activity induced by the hormone. Interestingly, strong stimulation of resorption overcomes this dependence on IL-6. Thus, parathyroid hormone likely induces multiple, redundant cytokines that can overcome the IL-6 requirement associated with moderate stimulation. Taken together with studies showing that many other bone resorptive agents also stimulate IL-6 production, our results suggest that IL-6 may be a downstream effector of these agents as well as of parathyroid hormone. Images PMID:7657797

  5. Inhibition of Osteoclastogenesis and Bone Resorption in vitro and in vivo by a prenylflavonoid xanthohumol from hops

    PubMed Central

    Li, Jing; Zeng, Li; Xie, Juan; Yue, Zhiying; Deng, Huayun; Ma, Xueyun; Zheng, Chunbing; Wu, Xiushan; Luo, Jian; Liu, Mingyao

    2015-01-01

    Excessive RANKL signaling leads to superfluous osteoclast formation and bone resorption, is widespread in the pathologic bone loss and destruction. Therefore, targeting RANKL or its signaling pathway has been a promising and successful strategy for this osteoclast-related diseases. In this study, we examined the effects of xanthohumol (XN), an abundant prenylflavonoid from hops plant, on osteoclastogenesis, osteoclast resorption, and RANKL-induced signaling pathway using both in vitro and in vivo assay systems. In mouse and human, XN inhibited osteoclast differentiation and osteoclast formation at the early stage. Furthermore, XN inhibited osteoclast actin-ring formation and bone resorption in a dose-dependent manner. In ovariectomized-induced bone loss mouse model and RANKL-injection-induced bone resorption model, we found that administration of XN markedly inhibited bone loss and resorption by suppressing osteoclast activity. At the molecular level, XN disrupted the association of RANK and TRAF6, resulted in the inhibition of NF-κB and Ca2+/NFATc1 signaling pathway during osteoclastogenesis. As a results, XN suppressed the expression of osteoclastogenesis-related marker genes, including CtsK, Nfatc1, Trap, Ctr. Therefore, our data demonstrated that XN inhibits osteoclastogenesis and bone resorption through RANK/TRAF6 signaling pathways. XN could be a promising drug candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis. PMID:26620037

  6. Simulation of the in vivo resorption rate of β-tricalcium phosphate bone graft substitutes implanted in a sheep model.

    PubMed

    Bashoor-Zadeh, Mahdieh; Baroud, Gamal; Bohner, Marc

    2011-09-01

    A few years ago, a model was proposed to predict the effect of the pore architecture of a bone graft substitute on its cell-mediated resorption rate. The aim of the present study was to compare the predictions of the model with the in vivo resorption rate of four β-tricalcium phosphate bone graft substitutes implanted in a sheep model. The simulation algorithm contained two main steps: (1) detection of the pores that could be accessed by blood vessels of 50 μm in diameter, and (2) removal of one solid layer at the surface of these pores. This process was repeated until full resorption occurred. Since the pore architecture was complex, μCT data and fuzzy imaging techniques were combined to reconstruct the precise bone graft substitute geometry and then image processing algorithms were developed to perform the resorption simulation steps. The proposed algorithm was verified by comparing its results with the analytical results of a simple geometry and experimental in-vivo data of β-TCP bone substitutes with more complex geometry. An excellent correlation (r(2)>0.9 for all 4 bone graft substitutes) was found between simulation results and in-vivo data, suggesting that this resorption model could be used to (i) better understand the in vivo behavior of bone graft substitutes resorbed by cell-mediation, and (ii) optimize the pore architecture of a bone graft substitute, for example to maximize its resorption rate.

  7. Cisplatin stimulates protein tyrosine phosphorylation in macrophages.

    PubMed

    Kumar, R; Shrivastava, A; Sodhi, A

    1995-03-01

    Cisplatin [cis-dichlorodiamine platinum (II)], a potent anti-tumor compound, stimulates immune responses by activating monocyte-macrophages and other cells of the immune system. The mechanism by which cisplatin activates these cells is poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event that mediates cellular responses, we examined whether cisplatin alters tyrosine phosphorylation in macrophages. We found that cisplatin increased tyrosine phosphorylation of several proteins in peritoneal macrophages and in P388D1 and IC-21 macrophage cell lines. Treatment of macrophages with tyrosine kinase inhibitors, genestein and lavendustin A, inhibited cisplatin-stimulated protein tyrosine phosphorylation in macrophages. Macrophages treated with cisplatin also exhibit increased fluorescence with anti-phosphotyrosine-FITC antibody. These data indicate that protein tyrosine phosphorylation plays a role in cisplatin-induced activation of macrophages. PMID:7539662

  8. Phenotypic Transitions of Macrophages Orchestrate Tissue Repair

    PubMed Central

    Novak, Margaret L.; Koh, Timothy J.

    2014-01-01

    Macrophages are essential for the efficient healing of numerous tissues, and they contribute to impaired healing and fibrosis. Tissue repair proceeds through overlapping phases of inflammation, proliferation, and remodeling, and macrophages are present throughout this progression. Macrophages exhibit transitions in phenotype and function as tissue repair progresses, although the precise factors regulating these transitions remain poorly defined. In efficiently healing injuries, macrophages present during a given stage of repair appear to orchestrate transition into the next phase and, in turn, can promote debridement of the injury site, cell proliferation and angiogenesis, collagen deposition, and matrix remodeling. However, dysregulated macrophage function can contribute to failure to heal or fibrosis in several pathological situations. This review will address current knowledge of the origins and functions of macrophages during the progression of tissue repair, with emphasis on skin and skeletal muscle. Dysregulation of macrophages in disease states and therapies targeting macrophage activation to promote tissue repair are also discussed. PMID:24091222

  9. Macrophage-induced thymic lymphocyte maturation.

    PubMed Central

    Van den Tweel, J G; Walker, W S

    1977-01-01

    Guinea-pig peritoneal macrophages were found to influence the functional maturation of thymic lymphocytes. Autologous thymic lymphocytes obtained from macrophage co-cultures responded to three different mitogens and were reduced in their ability to reassociate spontaneously with macrophages. Neither of these properties were found in thymic lymphocytes that had not been cultured with macrophages. These functional changes appeared to be specific for macrophages since thymic lymphocytes incubated with skin fibroblasts failed to respond to the test mitogens. Furthermore, they were not the result of either the inactivation, by macrophages, of a putative suppressor thymocyte or a soluble macrophage product. In addition to influencing the functional maturation of thymic lymphocytes, macrophages also appeared to play a direct role in inducing the mitogen response of functionally mature cells. PMID:304037

  10. Isolation and culture of murine macrophages.

    PubMed

    Davies, John Q; Gordon, Siamon

    2005-01-01

    The two most convenient sources of primary murine macrophages are the bone marrow and the peritoneal cavity. Resident peritoneal macrophages can readily be harvested from mice and purified by adherence to tissue culture plastic. The injection of Bio-Gel polyacrylamide beads or thioglycollate broth into the peritoneal cavity produces an inflammatory response allowing the purification of large numbers of elicited macrophages. The production of an activated macrophage population can be achieved by using Bacillus-Calmette-Guerin as the inflammatory stimulus. Resident bone marrow macrophages can be isolated following enzymatic separation of cells from bone marrow plugs and enrichment on 30% fetal calf serum containing medium or Ficoll-Hypaque gradients. Bone marrow-derived macrophages can be produced by differentiating nonadherent macrophage precursors with medium containing macrophage colony-stimulating factor.

  11. Macrophages and HIV-1: An Unhealthy Constellation.

    PubMed

    Sattentau, Quentin J; Stevenson, Mario

    2016-03-01

    Lentiviruses have a long-documented association with macrophages. Abundant evidence exists for in vitro and, in a tissue-specific manner, in vivo infection of macrophages by the primate lentiviruses HIV-1 and SIV. However, macrophage contribution to aspects of HIV-1 and SIV pathogenesis, and their role in viral persistence in individuals on suppressive antiretroviral therapy, remains unclear. Here we discuss recent evidence implicating macrophages in HIV-1-mediated disease and highlight directions for further investigation.

  12. Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

    PubMed Central

    Rojas, Joselyn; Salazar, Juan; Martínez, María Sofía; Palmar, Jim; Bautista, Jordan; Chávez-Castillo, Mervin; Gómez, Alexis; Bermúdez, Valmore

    2015-01-01

    Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD. PMID:26491604

  13. Investigation of macrophage polarization using bone marrow derived macrophages.

    PubMed

    Ying, Wei; Cheruku, Patali S; Bazer, Fuller W; Safe, Stephen H; Zhou, Beiyan

    2013-06-23

    The article describes a readily easy adaptive in vitro model to investigate macrophage polarization. In the presence of GM-CSF/M-CSF, hematopoietic stem/progenitor cells from the bone marrow are directed into monocytic differentiation, followed by M1 or M2 stimulation. The activation status can be tracked by changes in cell surface antigens, gene expression and cell signaling pathways.

  14. Tissue macrophage identity and self-renewal.

    PubMed

    Gentek, Rebecca; Molawi, Kaaweh; Sieweke, Michael H

    2014-11-01

    Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue-resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self-maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue-specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue-resident macrophages and how they differ from freshly recruited short-lived monocyte-derived cells. We examine whether macrophage proliferation can be qualified as self-renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self-renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self-renewal could be exploited for therapeutic intervention of macrophage-mediated pathologies by selectively targeting freshly recruited or resident macrophages.

  15. Modulating macrophage response to biomaterials

    NASA Astrophysics Data System (ADS)

    Zaveri, Toral

    Macrophages recruited to the site of biomaterial implantation are the primary mediators of the chronic foreign body response to implanted materials. Since foreign body response limits performance and functional life of numerous implanted biomaterials/medical devices, various approaches have been investigated to modulate macrophage interactions with biomaterial surfaces to mitigate this response. In this work we have explored two independent approaches to modulate the macrophage inflammatory response to biomaterials. The first approach targets surface integrins, cell surface receptors that mediate cell adhesion to biomaterials through adhesive proteins spontaneously adsorbed on biomaterial surfaces. The second approach involves surface modification of biomaterials using nanotopographic features since nanotopography has been reported to modulate cell adhesion and viability in a cell type-dependent manner. More specifically, Zinc Oxide (ZnO) nanorod surface was investigated for its role in modulating macrophage adhesion and survival in vitro and foreign body response in vivo. For the first approach, we have investigated the role of integrin Mac-1 and RGD-binding integrins in the in-vivo osteolysis response and macrophage inflammatory processes of phagocytosis as well as inflammatory cytokine secretion in response to particulate biomaterials. We have also investigated the in vivo foreign body response (FBR) to subcutaneously implanted biomaterials by evaluating the thickness of fibrous capsule formed around the implants after 2 weeks of implantation. The role of Mac-1 integrin was isolated using a Mac-1 KO mouse and comparing it to a WT control. The role of RGD binding integrins in FBR was investigated by coating the implanted biomaterial with ELVAX(TM) polymer loaded with Echistatin which contains the RGD sequence. For the in-vivo osteolysis study and to study the in-vitro macrophage response to particulate biomaterials, we used the RGD peptide encapsulated in ELVAX

  16. Changes in markers of bone formation and resorption in a bed rest model of weightlessness

    NASA Technical Reports Server (NTRS)

    Lueken, S. A.; Arnaud, S. B.; Taylor, A. K.; Baylink, D. J.

    1993-01-01

    To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

  17. Esculetin inhibits cartilage resorption induced by interleukin 1α in combination with oncostatin M

    PubMed Central

    Elliott, S; Rowan, A; Carrere, S; Koshy, P; Catterall, J; Cawston, T

    2001-01-01

    OBJECTIVE—To determine if a new inhibitor, esculetin (EST), can block resorption of cartilage.
METHODS—Interleukin 1α (IL1α, 0.04-5 ng/ml) and oncostatin M (OSM, 0.4-50 ng/ml) were used to stimulate the release of proteoglycan and collagen from bovine nasal cartilage and human articular cartilage in explant culture. Proteoglycan and collagen loss were assessed by dimethylmethylene blue and hydroxyproline assays, respectively. Collagenase levels were measured by assay of bioactivity and by enzyme linked immunosorbent assay (ELISA). The effects of EST on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the transformed human chondrocyte cell line T/C28a4 were assessed by northern blot analysis. TIMP-1 protein levels were assayed by ELISA. The effect of EST on the MMP-1 promoter was assessed using a promoter-luciferase construct in transient transfection studies.
RESULTS—EST inhibited proteoglycan and collagen resorption in a dose dependent manner with significant decreases seen at 66 µM and 100 µM EST, respectively. Collagenolytic activity was significantly decreased in bovine nasal cartilage cultures. In human articular cartilage, EST also inhibited IL1α + OSM stimulated resorption and decreased MMP-1 levels. TIMP-1 levels were not altered compared with controls. In T/C28a4 chondrocytes the IL1α + OSM induced expression of MMP-1, MMP-3, and MMP-13 mRNA was reduced to control levels by 250 µM EST. TIMP-1 mRNA levels were unaffected by EST treatment. All cytokine stimulation of an MMP-1 luciferase-promoter construct was lost in the presence of the inhibitor.
CONCLUSION—EST inhibits degradation of bovine nasal cartilage and human articular cartilage stimulated to resorb with IL1α + OSM.

 PMID:11156550

  18. Inhibition of bone resorption and growth of breast cancer in the bone microenvironment.

    PubMed

    Buijs, Jeroen T; Que, Ivo; Löwik, Clemens W G M; Papapoulos, Socrates E; van der Pluijm, Gabri

    2009-02-01

    Breast cancer frequently metastasizes to bone, where tumor cells induce osteoclasts to locally destroy bone. During bone resorption, growth factors are locally released that may support bone metastatic growth. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates and osteoprotegerin (OPG), are available for bone. We examined the hypothesis that inhibition of bone resorption by two different mechanisms may also affect the growth of cancer cells in bone. For this, we tested the effects of high doses of OPG and zoledronic acid (ZOL) on progression of MDA-231-B/Luc+ breast cancer cells in the bone microenvironment using whole body bioluminescent reporter imaging (BLI). Both treatments significantly inhibited the development of radiographically detectable osteolytic lesions. Histologic examination corroborated the radiographic findings, showing that both treatments preserved the integrity of bone trabeculae and prevented bone destruction (significantly higher trabecular bone volumes vs. vehicle). However, whereas practically no TRAcP-positive osteoclasts were observed in tibiae preparations of animals treated with Fc-OPG, TRAcP-positive osteoclasts were still present in the animals treated with ZOL. Intra-bone tumor burden was reduced with ZOL and Fc-OPG treatment. Although there appeared to be a trend for less overall total tumor burden upon treatment with both compounds, this was not significant as assessed by BLI and histomorphometric analysis due to the extramedullary growth of cancer cells which was not affected by these treatments. Collectively, anti-resorptive agents with different mechanisms of action - ZOL and OPG - significantly reduced cancer-induced osteolysis and intra-osseous tumor burden, but failed to restrain local tumor growth. However, interference with the bone micro-environmental growth support could still be of therapeutic relevance when given to patients early in the course of bone metastatic disease.

  19. Obesity phenotypes and resorption percentage after breast autologous fat grafting: Rule of low-grade inflammation

    PubMed Central

    Gentile, Pietro; Sarlo, Francesca; De Angelis, Barbara; De Lorenzo, Antonio; Cervelli, Valerio

    2016-01-01

    Background: One of the main reasons why the breast fat grafting was questioned is that there may be lipofilling resorption. In the literature, the resorption rate reported over the 1st year is highly variable (20–90%). Objective: The aim of this work was to identify the biochemical and clinical parameters, which increase fat graft maintenance in breast reconstruction. Materials and Methods: A sample of 19 patients was treated with fat grafting mixed with platelet-rich plasma. A complete screening of anthropometry, body composition, and blood biochemical parameters was assessed using the standardized equipment. Pre- and post-operative evaluation was performed, which included a complete clinical examination, photographic assessment, nuclear magnetic resonance imaging of the soft tissue, and ultrasound. The follow-up period was 2 years. Results: The authors divided the results into two types of patients: “responder” and “not a responder.” In the “responder” group patients with normal weight, gynoid fat distribution, obese, with normal blood biochemical parameters, and atherogenic indices but with high preoperative values of platelet-to-lymphocyte ratio (PLR) (174.49) and neutrophil-lymphocyte ratio (NLR) (2.65) showed a greater increase of fat graft maintenance at 6 and 12 months after the last lipofilling session. In the “not responder group” patients with overweight, android fat distribution, obese, high values of atherogenic indices, but with normal preoperative NLR and PLR ratios showed a lower fat graft maintenance at 6 and 12 months. Conclusion: We assume, the problem of fat resorption may be resolved by analysis of body composition and by examine the predictive role of preoperative markers of low-grade inflammation.

  20. Bone resorption is affected by follicular phase length in female rotating shift workers.

    PubMed Central

    Lohstroh, Pete N; Chen, Jiangang; Ba, Jianming; Ryan, Louise M; Xu, Xiping; Overstreet, James W; Lasley, Bill L

    2003-01-01

    Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT. PMID:12676625

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

    PubMed

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

    2012-01-01

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

  2. Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism.

    PubMed Central

    Howard, G A; Bottemiller, B L; Turner, R T; Rader, J I; Baylink, D J

    1981-01-01

    We have developed an in vitro system, using embryonic chicken tibiae grown in a serum-free medium, which exhibits simultaneous bone formation and resorption. Tibiae from 8-day embryos increased in mean (+/- SD) length (4.0 +/- 0.4 to 11.0 +/- 0.3 mm) and dry weight (0.30 +/- 0.04 to 0.84 +/- 0.04 mg) during 12 days in vitro. There was increased incorporation of [3H]proline into hydroxyproline (120 +/- 20 to 340 +/- 20 cpm/mg of bone per 24 hr) as a measure of collagen synthesis, as well as a 62 +/- 5% increase in total calcium and 45Ca taken up as an indication of active mineralization. A physiologic concentration (1 pM) of parathyroid hormone was found to stimulate bone resorption over control levels in this system. Parathyroid hormone stimulated the release of [3H]hydroxyproline from the bone shafts but not from the cartilage ends, indicating the specificity of the response. With 1 pM parathyroid hormone we observed an acute inhibition of bone formation, followed (after 12-16 hr) by a chronic stimulation of bone formation during the 12-day incubation. Both mineral uptake and matrix formation were enhanced at approximately the same rate during the 12-day incubation. The chronic enhancement of formation required parathyroid hormone only for the initial 8-10 hr of incubation. These results could be explained by the production or release of a factor from bone to stimulate formation in response to the acute increase in resorption--a "coupling factor." Indeed, dialyzed culture medium conditioned by actively resorbing bones stimulated bone formation over controls when added to organ cultures at a 1:20 dilution. The factor is larger than 12,000 daltons as determined by dialysis. The factor is specific for the bone shaft and did not affect the cartilage ends. PMID:6942425

  3. Effects of light emitting diode (LED) therapy at 940 nm on inflammatory root resorption in rats.

    PubMed

    Fonseca, Priscila D'Andrea; de Lima, Franciele Mendes; Higashi, Dayla Thyemi; Koyama, Débora Fernanda Volttani; Toginho Filho, Dari de Oliveira; Dias, Ivan Frederico Lupiano; Ramos, Solange de Paula

    2013-01-01

    The effects of LED therapy at 940 nm on periodontal healing, inflammatory cell infiltration, and root resorption were analyzed in an experimental model of orthodontic tooth movement in rats. Twenty-five male Wistar rats were allocated into four experimental groups: Control animals (Co, n = 5), Controls + LED therapy (CoLED, n = 6), animals submitted to orthodontic force (RR, n = 7) and submitted to orthodontic force + LED therapy (RRLED, n = 7). All procedures were approved by the Committee for Ethics in Animal Experimentation of the Universidade Estadual de Londrina (protocol CEEA 5/2010 37359). A force of 50 g was applied to the right upper molars of RR and RRLED groups. On days 2, 3, and 4 after orthodontic treatment, the CoLED and RRLED groups received LED irradiation (940 nm, 4 J/cm(2)). The animals were killed on day 7 for histological analysis. An increased number of root resorption lacunae was found only in the RR group (p < 0.05). The RR group also presented more osteoclasts (p < 0.005) and inflammatory cell infiltration (p < 0.005) than the control group. The RRLED group presented fewer osteoclasts (p < 0.005) and inflammatory cells (p < 0.005) in the periodontal ligament than the RR group. The CoLED and RRLED groups presented more periodontal fibroblasts (p < 0.005) than non-irradiated groups. RRLED presented more blood vessels (p < 0.01) in the periodontal ligament than the RR group. In conclusion, the results suggest that LED therapy improved periodontal tissue repair and decreased inflammation and root resorption after the application of orthodontic force.

  4. Obesity phenotypes and resorption percentage after breast autologous fat grafting: Rule of low-grade inflammation

    PubMed Central

    Gentile, Pietro; Sarlo, Francesca; De Angelis, Barbara; De Lorenzo, Antonio; Cervelli, Valerio

    2016-01-01

    Background: One of the main reasons why the breast fat grafting was questioned is that there may be lipofilling resorption. In the literature, the resorption rate reported over the 1st year is highly variable (20–90%). Objective: The aim of this work was to identify the biochemical and clinical parameters, which increase fat graft maintenance in breast reconstruction. Materials and Methods: A sample of 19 patients was treated with fat grafting mixed with platelet-rich plasma. A complete screening of anthropometry, body composition, and blood biochemical parameters was assessed using the standardized equipment. Pre- and post-operative evaluation was performed, which included a complete clinical examination, photographic assessment, nuclear magnetic resonance imaging of the soft tissue, and ultrasound. The follow-up period was 2 years. Results: The authors divided the results into two types of patients: “responder” and “not a responder.” In the “responder” group patients with normal weight, gynoid fat distribution, obese, with normal blood biochemical parameters, and atherogenic indices but with high preoperative values of platelet-to-lymphocyte ratio (PLR) (174.49) and neutrophil-lymphocyte ratio (NLR) (2.65) showed a greater increase of fat graft maintenance at 6 and 12 months after the last lipofilling session. In the “not responder group” patients with overweight, android fat distribution, obese, high values of atherogenic indices, but with normal preoperative NLR and PLR ratios showed a lower fat graft maintenance at 6 and 12 months. Conclusion: We assume, the problem of fat resorption may be resolved by analysis of body composition and by examine the predictive role of preoperative markers of low-grade inflammation. PMID:27656603

  5. [Progresses on macrophages of male reproductive tract].

    PubMed

    Li, Jing-Jing; Wang, Tao; Wang, Geng-Xin

    2002-12-01

    The review summarized the recent progress on macrophages of male reproductive tract and the action of macrophages on male reproductive physiology and pathology. The close correlation and effect between testicular macrophages and Leydig cells, Sertoli cells, germ cells, hypothalamic-pituitary-gonadal axis were introduced, respectively. At the same time, it pointed out the changes of macrophages' morphology and function in immune orchitis, and their regulation on the development of orchitis. So the complex immune regulation network in testes and testicular macrophages playing an important role on spermatogenesis and the stableness of spermatogenetic microenvironment in testes were further illuminated, which can provide theoretical basis for clinic therapy.

  6. Contribution of Macrophage Polarization to Metabolic Diseases.

    PubMed

    Komohara, Yoshihiro; Fujiwara, Yukio; Ohnishi, Koji; Shiraishi, Daisuke; Takeya, Motohiro

    2016-01-01

    Macrophage activation is one of the major immunological events in the pathogenesis of various diseases. Recent studies have disclosed that complicated mechanisms are involved in macrophage activation and polarization, and many published research articles have been based on the M1/M2 polarization concept. It is considered that M1- and M2-like macrophages are associated with T helper (Th)1-type and Th2-type immune responses, respectively, via several immune mediators. In this article, we summarize the correlations between macrophage polarization and metabolic disorders in both humans and mice and discuss the contribution of macrophage polarization to the pathogenic process of metabolic diseases.

  7. Effects of Nitrogen Addition on Nitrogen Resorption in Temperate Shrublands in Northern China

    PubMed Central

    Zhang, Jianhua; Li, He; Shen, Haihua; Chen, Yahan; Fang, Jingyun; Tang, Zhiyao

    2015-01-01

    Nutrient resorption from senescing leaves is a key mechanism of nutrient conservation for plants. The nutrient resorption efficiency is highly dependent on leaf nutrient status, species identity and soil nutrient availability. Nitrogen is a limiting nutrient in most ecosystems, it is widely reported that nitrogen resorption efficiency (NRE) was highly dependent on the soil nitrogen availability and vary with N deposition. The effects of nitrogen deposition on NRE and nitrogen concentration in green and senescing leaves have been well established for forests and grasslands; in contrast, little is known on how plants in shrublands respond to nitrogen deposition across the world. In this study, we conducted a two-year nitrogen addition manipulation experiment to explore the responses of nitrogen concentration in green and senescing leaves, and NRE of seven dominant species, namely, Vitex negundo, Wikstroemia chamaedaphne, Carex rigescens and Cleistogenes chinensis from the Vitex negundo community, and Spirea trilobata, Armeniaca sibirica, V. negundo, C. rigescens and Spodiopogon sibiricus from the Spirea trilobata community, to nitrogen deposition in two typical shrub communities of Mt. Dongling in northern China. Results showed that NRE varied remarkably among different life forms, which was lowest in shrubs, highest in grasses, and intermediate in forbs, implying that shrubs may be most capable of obtaining nitrogen from soil, grasses may conserve more nitrogen by absorption from senescing leaves, whereas forbs may adopt both mechanisms to compete for limited nitrogen supply from the habitats. As the N addition rate increases, N concentration in senescing leaves ([N]s) increased consistent from all species from both communities, that in green leaves ([N]g) increased for all species from the Vitex negundo community, while no significant responses were found for all species from the Spirea trilobata community; NRE decreased for all species except A. sibirica from the

  8. Mineral metabolism in isolated mouse long bones: Opposite effects of microgravity on mineralization and resorption

    NASA Technical Reports Server (NTRS)

    Veldhuijzen, Jean Paul; Vanloon, Jack J. W. A.

    1994-01-01

    An experiment using isolated skeletal tissues under microgravity, is reported. Fetal mouse long bones (metatarsals) were cultured for 4 days in the Biorack facility of Spacelab during the IML-1 (International Microgravity Laboratory) mission of the Space Shuttle. Overall growth was not affected, however glucose consumption was significantly reduced under microgravity. Mineralization of the diaphysis was also strongly reduced under microgravity as compared to the on-board 1 g group. In contrast, mineral resorption by osteoclasts was signficantly increased. These results indicate that these fetal mouse long bones are a sensitive and useful model to further study the cellular mechanisms involved in the changed mineral metabolism of skeletal tissues under microgravity.

  9. Is the Resorption of Grafted Fat Reduced in Cell-Assisted Lipotransfer for Breast Augmentation?

    PubMed

    Wang, Lin; Luo, Xuan; Lu, Yi; Fan, Zhi-Hong; Hu, Xiang

    2015-08-01

    Cell-assisted lipotransfer (CAL) is a cotransplantation of adipose tissue and stromal vascular fraction (SVF) including adipose-derived stem cells. But although CAL can get satisfactory outcomes in breast augmentation, the resorption of the grafted fat is still unclear. A total of 12 patients received breast augmentation using CAL. All of them completed 6 months of follow-up. In 1 mini-CAL case, 500-mL liposuction fluid was used to harvest the SVF cells. In 11 full-CAL cases, 250-mL aspirated fat was needed apart from 500-mL liposuction fluid. The percentage of adipose-derived stem cells in SVF cells was detected using flow cytometry and their multilineage potential ability was assessed with in vitro induction. The volumes of breasts and pectoral muscle were measured, and radiological image change was analyzed using magnetic resonance imaging before the operation and 3 and 6 months after the operation. Additionally, the subjective evaluation on the cosmetic outcomes was determined by surgeons and patients. Adipose-derived stem cells in SVF cells accounted for 40.27% and 3.34% in full-CAL cases and mini-CAL cases, respectively. Postoperative atrophy occurred within the first 3 months. At the 6 months postoperatively, breast volume is augmented, ranging from 60.71 to 197 mL, with a mean value of 125.35 (45.49) mL. The ultimate resorption of grafted fat at the 6 months postoperatively is 51.84% (16.74%). Newly formed cysts and nodules were detected in 2 cases. No calcification was found in all magnetic resonance images. Only 1 patient was unsatisfied with the cosmetic outcome. Our preliminary study displayed a satisfactory augmented volume with little complications using CAL for breast augmentation. But the resorption at the 6 months postoperatively [51.84% (16.74%)] showed no significant advantage over non-CAL technique (40%-60% reported), which suggested that SVF cells harvested from 250-mL aspirated fat and 500-mL liposuction fluid were insufficient to average 250

  10. Macrophage Polarization during Murine Lyme Borreliosis.

    PubMed

    Lasky, Carrie E; Olson, Rachel M; Brown, Charles R

    2015-07-01

    Infection of C3H mice with Borrelia burgdorferi, the causative agent of Lyme disease, reliably produces an infectious arthritis and carditis that peak around 3 weeks postinfection and then spontaneously resolve. Macrophage polarization has been suggested to drive inflammation, the clearance of bacteria, and tissue repair and resolution in a variety of infectious disease models. During Lyme disease it is clear that macrophages are capable of clearing Borrelia spirochetes and exhausted neutrophils; however, the role of macrophage phenotype in disease development or resolution has not been studied. Using classical (NOS2) and alternative (CD206) macrophage subset-specific markers, we determined the phenotype of F4/80(+) macrophages within the joints and heart throughout the infection time course. Within the joint, CD206(+) macrophages dominated throughout the course of infection, and NOS2(+) macrophage numbers became elevated only during the peak of inflammation. We also found dual NOS2(+) CD206(+) macrophages which increased during resolution. In contrast to findings for the ankle joints, numbers of NOS2(+) and CD206(+) macrophages in the heart were similar at the peak of inflammation. 5-Lipoxygenase-deficient (5-LOX(-/-)) mice, which display a failure of Lyme arthritis resolution, recruited fewer F4/80(+) cells to the infected joints and heart, but macrophage subset populations were unchanged. These results highlight differences in the inflammatory infiltrates during Lyme arthritis and carditis and demonstrate the coexistence of multiple macrophage subsets within a single inflammatory site.

  11. Identification of polarized macrophage subsets in zebrafish

    PubMed Central

    Nguyen-Chi, Mai; Laplace-Builhe, Béryl; Travnickova, Jana; Luz-Crawford, Patricia; Tejedor, Gautier; Phan, Quang Tien; Duroux-Richard, Isabelle; Levraud, Jean-Pierre; Kissa, Karima; Lutfalla, Georges

    2015-01-01

    While the mammalian macrophage phenotypes have been intensively studied in vitro, the dynamic of their phenotypic polarization has never been investigated in live vertebrates. We used the zebrafish as a live model to identify and trail macrophage subtypes. We generated a transgenic line whose macrophages expressing tumour necrosis factor alpha (tnfa), a key feature of classically activated (M1) macrophages, express fluorescent proteins Tg(mpeg1:mCherryF/tnfa:eGFP-F). Using 4D-confocal microscopy, we showed that both aseptic wounding and Escherichia coli inoculation triggered macrophage recruitment, some of which started to express tnfa. RT-qPCR on Fluorescence Activated Cell Sorting (FACS)-sorted tnfa+ and tnfa− macrophages showed that they, respectively, expressed M1 and alternatively activated (M2) mammalian markers. Fate tracing of tnfa+ macrophages during the time-course of inflammation demonstrated that pro-inflammatory macrophages converted into M2-like phenotype during the resolution step. Our results reveal the diversity and plasticity of zebrafish macrophage subsets and underline the similarities with mammalian macrophages proposing a new system to study macrophage functional dynamic. DOI: http://dx.doi.org/10.7554/eLife.07288.001 PMID:26154973

  12. Macrophages and cellular immunity in Drosophila melanogaster.

    PubMed

    Gold, Katrina S; Brückner, Katja

    2015-12-01

    The invertebrate Drosophila melanogaster has been a powerful model for understanding blood cell development and immunity. Drosophila is a holometabolous insect, which transitions through a series of life stages from embryo, larva and pupa to adulthood. In spite of this, remarkable parallels exist between Drosophila and vertebrate macrophages, both in terms of development and function. More than 90% of Drosophila blood cells (hemocytes) are macrophages (plasmatocytes), making this highly tractable genetic system attractive for studying a variety of questions in macrophage biology. In vertebrates, recent findings revealed that macrophages have two independent origins: self-renewing macrophages, which reside and proliferate in local microenvironments in a variety of tissues, and macrophages of the monocyte lineage, which derive from hematopoietic stem or progenitor cells. Like vertebrates, Drosophila possesses two macrophage lineages with a conserved dual ontogeny. These parallels allow us to take advantage of the Drosophila model when investigating macrophage lineage specification, maintenance and amplification, and the induction of macrophages and their progenitors by local microenvironments and systemic cues. Beyond macrophage development, Drosophila further serves as a paradigm for understanding the mechanisms underlying macrophage function and cellular immunity in infection, tissue homeostasis and cancer, throughout development and adult life. PMID:27117654

  13. Tissue-Resident Macrophage Ontogeny and Homeostasis.

    PubMed

    Ginhoux, Florent; Guilliams, Martin

    2016-03-15

    Defining the origins and developmental pathways of tissue-resident macrophages should help refine our understanding of the role of these cells in various disease settings and enable the design of novel macrophage-targeted therapies. In recent years the long-held belief that macrophage populations in the adult are continuously replenished by monocytes from the bone marrow (BM) has been overturned with the advent of new techniques to dissect cellular ontogeny. The new paradigm suggests that several tissue-resident macrophage populations are seeded during waves of embryonic hematopoiesis and self-maintain independently of BM contribution during adulthood. However, the exact nature of the embryonic progenitors that give rise to adult tissue-resident macrophages is still debated, and the mechanisms enabling macrophage population maintenance in the adult are undefined. Here, we review the emergence of these concepts and discuss current controversies and future directions in macrophage biology. PMID:26982352

  14. Macrophages in Tissue Repair, Regeneration, and Fibrosis.

    PubMed

    Wynn, Thomas A; Vannella, Kevin M

    2016-03-15

    Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.

  15. Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow. Evidence for autonomy from factors released during bone resorption.

    PubMed Central

    Jilka, R L; Takahashi, K; Munshi, M; Williams, D C; Roberson, P K; Manolagas, S C

    1998-01-01

    Loss of sex steroids causes an increase in both the resorption and formation of bone, with the former exceeding the latter. Based on evidence that the increased bone resorption after estrogen loss is due to an increase in osteoclastogenesis, we hypothesized that estrogen loss also stimulates osteoblastogenesis. We report that the number of mesenchymal osteoblast progenitors in the murine bone marrow was increased two- to threefold between 2 and 8 wk after ovariectomy and returned to control levels by 16 wk. Circulating osteocalcin, as well as osteoclastogenesis and the rate of bone loss, followed a very similar temporal pattern. Inhibition of bone resorption by administration of the bisphosphonate alendronate led to a decrease of the absolute number of osteoblast progenitors; however, it did not influence the stimulating effect of ovariectomy on osteoblastogenesis or osteoclastogenesis. These observations indicate that the increased bone formation that follows loss of estrogen can be explained, at least in part, by an increase in osteoblastogenesis. Moreover, they strongly suggest that unlike normal bone remodeling, whereby osteoblast development is stimulated by factors released from the bone matrix during osteoclastic resorption, estrogen deficiency unleashes signals that can stimulate the differentiation of osteoblast progenitors in a fashion that is autonomous from the need created by bone resorption, and therefore, inappropriate. PMID:9576759

  16. Extended leaf senescence promotes carbon gain and nutrient resorption: importance of maintaining winter photosynthesis in subtropical forests.

    PubMed

    Zhang, Yong-Jiang; Yang, Qiu-Yun; Lee, David W; Goldstein, Guillermo; Cao, Kun-Fang

    2013-11-01

    The relative advantages of being deciduous or evergreen in subtropical forests and the relationship between leaf phenology and nutrient resorption efficiency are not well understood. The most successful deciduous species (Lyonia ovalifolia) in an evergreen-dominated subtropical montane cloud forest in southwest (SW) China maintains red senescing leaves throughout much of the winter. The aim of this study was to investigate whether red senescing leaves of this species were able to assimilate carbon in winter, to infer the importance of maintaining a positive winter carbon balance in subtropical forests, and to test whether an extended leaf life span is associated with enhanced nutrient resorption and yearly carbon gain. The red senescing leaves of L. ovalifolia assimilated considerable carbon during part of the winter, resulting in a higher yearly carbon gain than co-occurring deciduous species. Its leaf N and P resorption efficiency was higher than for co-occurring non-anthocyanic deciduous species that dropped leaves in autumn, supporting the hypothesis that anthocyanin accumulation and/or extended leaf senescence help in nutrient resorption. Substantial winter carbon gain and efficient nutrient resorption may partially explain the success of L. ovalifolia versus that of the other deciduous species in this subtropical forest. The importance of maintaining a positive carbon balance for ecological success in this forest also provides indirect evidence for the dominance of evergreen species in the subtropical forests of SW China.

  17. Extended leaf senescence promotes carbon gain and nutrient resorption: importance of maintaining winter photosynthesis in subtropical forests.

    PubMed

    Zhang, Yong-Jiang; Yang, Qiu-Yun; Lee, David W; Goldstein, Guillermo; Cao, Kun-Fang

    2013-11-01

    The relative advantages of being deciduous or evergreen in subtropical forests and the relationship between leaf phenology and nutrient resorption efficiency are not well understood. The most successful deciduous species (Lyonia ovalifolia) in an evergreen-dominated subtropical montane cloud forest in southwest (SW) China maintains red senescing leaves throughout much of the winter. The aim of this study was to investigate whether red senescing leaves of this species were able to assimilate carbon in winter, to infer the importance of maintaining a positive winter carbon balance in subtropical forests, and to test whether an extended leaf life span is associated with enhanced nutrient resorption and yearly carbon gain. The red senescing leaves of L. ovalifolia assimilated considerable carbon during part of the winter, resulting in a higher yearly carbon gain than co-occurring deciduous species. Its leaf N and P resorption efficiency was higher than for co-occurring non-anthocyanic deciduous species that dropped leaves in autumn, supporting the hypothesis that anthocyanin accumulation and/or extended leaf senescence help in nutrient resorption. Substantial winter carbon gain and efficient nutrient resorption may partially explain the success of L. ovalifolia versus that of the other deciduous species in this subtropical forest. The importance of maintaining a positive carbon balance for ecological success in this forest also provides indirect evidence for the dominance of evergreen species in the subtropical forests of SW China. PMID:23636462

  18. Influences of Fucoxanthin on Alveolar Bone Resorption in Induced Periodontitis in Rat Molars

    PubMed Central

    Kose, Oguz; Arabaci, Taner; Yemenoglu, Hatice; Kara, Adem; Ozkanlar, Seckin; Kayis, Sevki; Duymus, Zeynep Yesil

    2016-01-01

    The aim of this study was to evaluate the effects of systemic fucoxanthin treatment on alveolar bone resorption in rats with periodontitis. Thirty rats were divided into control, experimental periodontitis (EP), and experimental periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature for four weeks. After removal of the ligature, the rats in the EP-FUCO group were treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28 consecutive days. At the end of the study, all of the rats were euthanized and intracardiac blood and mandible tissue samples were obtained for biochemical, immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in a slight decrease in tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and a significant decrease in oxidative stress index. It was observed that fucoxanthin caused a significant reduction in receptor activator of nuclear factor kappa-β ligand (RANKL) levels and a statistically non-significant elevation in osteoprotegerin and bone-alkaline phosphatase levels. There were no significant differences in alveolar bone loss levels between the EP and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a limited reduction in alveolar bone resorption in rats with periodontitis. One of the mechanisms underlying the mentioned limited effect might be related to the ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated osteoclastogenesis. PMID:27043583

  19. Directional and temporal variation of the mechanical properties of robocast scaffold during resorption.

    PubMed

    Waygood, J; Murch, G E; Fiedler, T

    2015-09-01

    This paper addresses the mechanical behavior of robocast PCL-Bioglass(®) scaffolds. These structures can be used as 3rd generation implants in tissue engineering to support the regrowth of damaged tissue, in particular bone. After successful tissue regeneration the scaffolds slowly dissolve leaving no foreign material permanently inside the body. However, to avoid mechanical separation from surrounding tissue they must exhibit similar mechanical properties. The present study introduces a detailed numerical study focusing on the determination of effective mechanical material properties, their anisotropy, and mechanical degradation due to scaffold resorption. In order to accurately capture the complex scaffold geometry, micro-computed tomography scans of actual samples are conducted. The resulting three-dimensional data are directly converted into finite element calculation models. Numerical compressive tests of these unmodified models are repeated for three perpendicular directions to investigate mechanical anisotropy, after which the effect of scaffold degradation due to exposure to body fluid is simulated. To this end, two different resorption models, namely surface erosion and bulk degradation, are applied to the micro-computed tomography data. The modified geometry data are then converted into calculation models and numerical compression tests then allow the prediction of the mechanical properties of partially resorbed scaffolds.

  20. Embryo resorption following administration of steroidal compounds to rats in mid pregnancy.

    PubMed Central

    Sarkar, K; Kinson, G A; Rowsell, H C

    1986-01-01

    In the course of experiments on the effects of anabolic steroids on the myocardium of rat conceptuses, we found that subcutaneous implantation of 10 mg of estradiol, Dianabol or testosterone to rats in mid pregnancy, resulted in embryo resorption. Placental tissue was identified only in estradiol-treated rats which also demonstrated a large amount of serosanguineous fluid that dilated the horns considerably. The yellow nodules of placental attachment sites were represented histologically by cellular and vascular proliferations between the inner and outer layers of the myometrium. The nodular aggregates of cells had variable features according to the steroid administered. Neither decidual cells nor metrial glands that are reported to be the constituents of placental attachment sites were seen in our material. We conclude that anabolic steroids are potent agents for embryo resorption, and that the cells in the nodules of placental attachment sites are likely to be derived from the myometrium. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:3742378

  1. Accuracy of digital periapical radiography and cone-beam computed tomography in detecting external root resorption

    PubMed Central

    Geha, Hassem; Sankar, Vidya; Teixeira, Fabricio B.; McMahan, Clyde Alex; Noujeim, Marcel

    2015-01-01

    Purpose The purpose of this study was to evaluate and compare the efficacy of cone-beam computed tomography (CBCT) and digital intraoral radiography in diagnosing simulated small external root resorption cavities. Materials and Methods Cavities were drilled in 159 roots using a small spherical bur at different root levels and on all surfaces. The teeth were imaged both with intraoral digital radiography using image plates and with CBCT. Two sets of intraoral images were acquired per tooth: orthogonal (PA) which was the conventional periapical radiograph and mesioangulated (SET). Four readers were asked to rate their confidence level in detecting and locating the lesions. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of each modality in detecting the presence of lesions, the affected surface, and the affected level. Analysis of variation was used to compare the results and kappa analysis was used to evaluate interobserver agreement. Results A significant difference in the area under the ROC curves was found among the three modalities (P=0.0002), with CBCT (0.81) having a significantly higher value than PA (0.71) or SET (0.71). PA was slightly more accurate than SET, but the difference was not statistically significant. CBCT was also superior in locating the affected surface and level. Conclusion CBCT has already proven its superiority in detecting multiple dental conditions, and this study shows it to likewise be superior in detecting and locating incipient external root resorption. PMID:26389057

  2. BAR Proteins PSTPIP1/2 Regulate Podosome Dynamics and the Resorption Activity of Osteoclasts

    PubMed Central

    Sztacho, Martin; Segeletz, Sandra; Sanchez-Fernandez, Maria Arantzazu; Czupalla, Cornelia; Niehage, Christian; Hoflack, Bernard

    2016-01-01

    Bone resorption in vertebrates relies on the ability of osteoclasts to assemble F-actin-rich podosomes that condense into podosomal belts, forming sealing zones. Sealing zones segregate bone-facing ruffled membranes from other membrane domains, and disassemble when osteoclasts migrate to new areas. How podosome/sealing zone dynamics is regulated remains unknown. We illustrate the essential role of the membrane scaffolding F-BAR-Proline-Serine-Threonine Phosphatase Interacting Proteins (PSTPIP) 1 and 2 in this process. Whereas PSTPIP2 regulates podosome assembly, PSTPIP1 regulates their disassembly. PSTPIP1 recruits, through its F-BAR domain, the protein tyrosine phosphatase non-receptor type 6 (PTPN6) that de-phosphophorylates the phosphatidylinositol 5-phosphatases SHIP1/2 bound to the SH3 domain of PSTPIP1. Depletion of any component of this complex prevents sealing zone disassembly and increases osteoclast activity. Thus, our results illustrate the importance of BAR domain proteins in podosome structure and dynamics, and identify a new PSTPIP1/PTPN6/SHIP1/2-dependent negative feedback mechanism that counterbalances Src and PI(3,4,5)P3 signalling to control osteoclast cell polarity and activity during bone resorption. PMID:27760174

  3. Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation.

    PubMed

    Takeshita, Sunao; Fumoto, Toshio; Matsuoka, Kazuhiko; Park, Kyoung-ae; Aburatani, Hiroyuki; Kato, Shigeaki; Ito, Masako; Ikeda, Kyoji

    2013-09-01

    Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts and is key to the maintenance of bone integrity. While bone matrix-mobilized growth factors, such as TGF-β, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule serves as a coupling factor for bone resorption to formation. We found that CTHRC1, a protein secreted by mature bone-resorbing osteoclasts, targets stromal cells to stimulate osteogenesis. Cthrc1 expression was robustly induced when mature osteoclasts were placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increased in a high-turnover state (such as that induced by RANKL injections in vivo), but decreased in conditions associated with suppressed bone turnover (such as with aging and after alendronate treatment). Targeted deletion of Cthrc1 in mice eliminated Cthrc1 expression in bone, whereas its deficiency in osteoblasts did not exert any significant effect. Osteoclast-specific deletion of Cthrc1 resulted in osteopenia due to reduced bone formation and impaired the coupling process after resorption induced by RANKL injections, impairing bone mass recovery. These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling.

  4. Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion.

    PubMed

    Nabavi, Noushin; Khandani, Arian; Camirand, Anne; Harrison, Rene E

    2011-11-01

    Exposure to microgravity has been associated with several physiological changes in astronauts, including an osteoporosis-like loss in bone mass. Despite many in vivo and in vitro studies in both microgravity and simulated microgravity conditions, the mechanism for bone loss is still not clear. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to assess bone cell responses. In this work, we conduct a unique investigation of the effects of microgravity on bone-producing osteoblasts and, in parallel, on bone-resorbing osteoclasts. An increase in total number of discrete resorption pits is observed in osteoclasts that experienced microgravity versus ground controls. We further show that osteoblasts exposed to 5 days of microgravity have shorter and wavier microtubules (MTs), smaller and fewer focal adhesions, and thinner cortical actin and stress fibers. Space-flown osteoblasts present extended cell shapes as well as significantly more disrupted and often fragmented or condensed nuclei. The absence of gravitational forces therefore causes both an increase in bone resorption by osteoclasts, and a decrease in osteoblast cellular integrity. The observed effects on both major bone cell types likely accelerate bone loss in microgravity environments, and additionally offer a potential explanation to the development of disuse osteoporosis on Earth. PMID:21839189

  5. Short-term effects of fluoride and strontium on bone formation and resorption in the mouse.

    PubMed

    Marie, P J; Hott, M

    1986-06-01

    The early effects of sodium fluoride (0.80 mg/kg/d) and strontium chloride (0.27%) given alone, or in combination in drinking water, on bone metabolism were examined in the mouse using dynamic histomorphometric methods. Four weeks of oral strontium supplementation increased the osteoid surface and reduced the number of acid phosphatase-stained osteoclasts. However the trabecular calcified bone volume was not augmented. By contrast, short-term treatment with fluoride produced a rapid stimulatory effect on bone formation at a dose that did not affect the bone mineralization rate. Four weeks of fluoride supplementation induced a rapid 21.1% increase in the osteoblastic surface and a 26.3% stimulation of the bone matrix apposition rate evaluated by the double tritiated proline labelling method, which resulted in a 29% increase in the amount of osteoid. This rapid stimulation of the bone formation rate without detectable change in osteoclastic bone resorption led to a 12% increase in the trabecular calcified bone density. This study shows that fluoride and strontium produce distinct early effects on bone formation and resorption in the mouse and that fluoride exerts a rapid stimulatory effect on the bone matrix synthesis rate through an augmentation of the number of bone-forming cells. PMID:3713515

  6. Follicle-stimulating hormone enhances alveolar bone resorption via upregulation of cyclooxygenase-2

    PubMed Central

    Zhu, Chunxia; Ji, Yaoting; Liu, Shengbo; Bian, Zhuan

    2016-01-01

    This study aimed to investigate whether follicle-stimulating hormone (FSH)-induced alveolar bone resorption was mediated by a cyclooxygenase 2 (COX-2) enzyme related mechanism. Experimental periodontitis was induced in bilateral ovariectomized (OVX) rats, some of which were injected with triptorelin, an FSH inhibitor. After mandibles were collected, we performed micro-computed tomography to evaluate alveolar bone loss and immunohistochemical staining to assess COX-2 expression. As well, human periodontal ligament cells (PDLCs) were treated with FSH (30 ng/ml), and the COX-2 mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction (qPCR) and Western blotting, respectively; prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that FSH significantly increased alveolar bone resorption and the expression of COX-2 in the bilateral OVX + Ligatured rats compared with the other treatment groups. FSH also increased the mRNA and protein expression of COX-2 and PGE2 (P < 0.01) in human PDLCs. Further, the analysis of signaling pathways revealed the activation of COX-2-mediated pathways including Erk, p38, and Akt. These data suggest that FSH aggravates alveolar bone loss via a COX-2-upregulation mechanism and that the Erk, p38, and Akt pathways are involved in this pathological process. PMID:27725865

  7. Inhibition of Osteoclastogenesis and Inflammatory Bone Resorption by Targeting BET Proteins and Epigenetic Regulation

    PubMed Central

    Park-Min, Kyung-Hyun; Lim, Elisha; Lee, Min Joon; Park, Sung Ho; Giannopoulos, Eugenia; Yarilina, Anna; van der Meulen, Marjolein; Zhao, Baohong; Smithers, Nicholas; Witherington, Jason; Lee, Kevin; Tak, Paul P.; Prinjha, Rab K.; Ivashkiv, Lionel B.

    2014-01-01

    Emerging evidence suggests that RANKL-induced changes in chromatin state are important for osteoclastogenesis, but these epigenetic mechanisms are not well understood and have not been therapeutically targeted. In this study we find that the small molecule I-BET151 that targets bromo and extra-terminal (BET) proteins that “read” chromatin states by binding to acetylated histones strongly suppresses osteoclastogenesis. I-BET151 suppresses pathologic bone loss in TNF-induced inflammatory osteolysis, inflammatory arthritis, and post-ovariectomy models. Transcriptome analysis identifies a MYC-NFAT axis important for osteoclastogenesis. Mechanistically, I-BET151 inhibits expression of the master osteoclast regulator NFATC1 by suppressing expression and recruitment of its newly identified upstream regulator MYC. MYC is elevated in rheumatoid arthritis and its induction by RANKL is important for osteoclastogenesis and TNF-induced bone resorption. These findings highlight the importance of an I-BET151-inhibited MYC-NFAT axis in osteoclastogenesis, and suggest targeting epigenetic chromatin regulators holds promise for treatment of inflammatory and estrogen deficiency-mediated pathologic bone resorption. PMID:25391636

  8. Biocompatibility, resorption and biofunctionality of a new synthetic biodegradable membrane for guided bone regeneration.

    PubMed

    Hoornaert, Alain; d'Arros, Cyril; Heymann, Marie-Francoise; Layrolle, Pierre

    2016-01-01

    Membranes for guided bone regeneration (GBR) were prepared from the synthetic biodegradable polymer poly-D,L-lactic/glycolic acid (PLGA). This GBR membrane has a bi-layered structure with a dense film to prevent gingival fibroblast ingrowth and ensure mechanical function, and a micro-fibrous layer to support colonization by osteogenic cells and promote bone regeneration. Hydrolysis and biodegradation were both studied in vitro through soaking in phosphate buffered saline (PBS) and in vivo by implantation in the subcutis of rats for 4, 8, 16, 26, 48 and 52 weeks. Histology revealed an excellent colonization of the micro-fibrous layer by cells with a minimal inflammatory reaction during resorption. GBR using the synthetic PLGA membrane was evaluated on critical-size calvaria defects in rats for 4 and 8 weeks. Radiographs, micro-computed tomography and histology showed bone regeneration with the PLGA membrane, while the defects covered with a collagen membrane showed a limited amount of mineralized bone, similar to that of the defect left empty. The biofunctionality of the PLGA membranes was also compared to collagen membranes in mandible defects in rabbits, associated or not with beta-tricalcium phosphate granules. This study revealed that the bi-layered synthetic membrane made of PLGA was safer, more biocompatible, and had a greater controlled resorption rate and bone regeneration capacity than collagen membranes. This new PLGA membrane could be used in pre-implantology and peri-odontology surgery. PMID:27509180

  9. Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion.

    PubMed

    Nabavi, Noushin; Khandani, Arian; Camirand, Anne; Harrison, Rene E

    2011-11-01

    Exposure to microgravity has been associated with several physiological changes in astronauts, including an osteoporosis-like loss in bone mass. Despite many in vivo and in vitro studies in both microgravity and simulated microgravity conditions, the mechanism for bone loss is still not clear. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to assess bone cell responses. In this work, we conduct a unique investigation of the effects of microgravity on bone-producing osteoblasts and, in parallel, on bone-resorbing osteoclasts. An increase in total number of discrete resorption pits is observed in osteoclasts that experienced microgravity versus ground controls. We further show that osteoblasts exposed to 5 days of microgravity have shorter and wavier microtubules (MTs), smaller and fewer focal adhesions, and thinner cortical actin and stress fibers. Space-flown osteoblasts present extended cell shapes as well as significantly more disrupted and often fragmented or condensed nuclei. The absence of gravitational forces therefore causes both an increase in bone resorption by osteoclasts, and a decrease in osteoblast cellular integrity. The observed effects on both major bone cell types likely accelerate bone loss in microgravity environments, and additionally offer a potential explanation to the development of disuse osteoporosis on Earth.

  10. Bone Resorption Increases as Early as the Second Day in Head- Down Bed Rest

    NASA Astrophysics Data System (ADS)

    Heer, M.; Kamps, N.; Mika, C.; Boese, A.; Gerzer, R.

    Long-term bed rest and space mission studies have shown that immobilization as well as microgravity induce increased bone resorption while bone formation tends to decrease. In order to analyze the kinetics of short-term changes in bone turnover we studied in a randomized, strictly controlled crossover design the effects of 6 days 6° head-down tilt bed rest (HDT) in 8 male healthy subjects (mean body weight (BW): 70.1 +/- 1.88 kg; mean age: 25.5 +/- 1.04 years) in our metabolic ward. Two days before arriving in the metabolic ward the subjects started with a diet consisting of an energy content of 10 MJ/d, 2000 mg Calcium/d, 400 i.U. Vitamin D, 200 mEq Na+ and 50 ml water/kg BW/d. The diet was continued in the metabolic ward. The metabolic ward period (11days) was divided into 3 parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers, namely C-telopeptide (CTX) and N-telopeptide (NTX). On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers (bone Alkaline Phosphatase (bAP), Procollagen-I-Propeptide (P-I-CP). Both study phases were identical with respect to environmental conditions, study protocol and diet. Urinary calcium excretion was as early as the first day in immobilization increased (p<0.01). CTX- and NTX-excretion stayed unchanged the first 24 hours in HDT compared to the control. But, already on the 2nd day of immobilization both bone resorption markers significantly increased. NTX-excretion was increased by 28.7 +/- 14.0% (p<0.05), while CTX-excretion rose by 17.8 +/- 8.3% (p<0.01). Both, the CTX- excretion as well as the calcium excretion keep the significantly higher level during the HDT period, and even continued through the first day of recovery. However, NTX excretion, descended from day

  11. Identification of enoxacin as an inhibitor of osteoclast formation and bone resorption by structure-based virtual screening.

    PubMed

    Ostrov, David A; Magis, Andrew T; Wronski, Thomas J; Chan, Edward K L; Toro, Edgardo J; Donatelli, Richard E; Sajek, Kristen; Haroun, Ireni N; Nagib, Michael I; Piedrahita, Ana; Harris, Ashley; Holliday, L Shannon

    2009-08-27

    An interaction between the B2 subunit of vacuolar H(+)-ATPase (V-ATPase) and microfilaments is required for osteoclast bone resorption. An atomic homology model of the actin binding site on B2 was generated and molecular docking simulations were performed. Enoxacin, a fluoroquinolone antibiotic, was identified and in vitro testing demonstrated that enoxacin blocked binding between purified B2 and microfilaments. Enoxacin dose dependently reduced the number of osteoclasts differentiating in mouse marrow cultures stimulated with 1,25-dihydroxyvitamin D(3), as well as markers of osteoclast activity, and the number of resorption lacunae formed on bone slices. Enoxacin inhibited osteoclast formation at concentrations where osteoblast formation was not altered. In summary, enoxacin is a novel small molecule inhibitor of osteoclast bone resorption that acts by an unique mechanism and is therefore an attractive lead molecule for the development of a new class of antiosteoclastic agents.

  12. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice.

    PubMed Central

    Kitazawa, R; Kimble, R B; Vannice, J L; Kung, V T; Pacifici, R

    1994-01-01

    To investigate the contribution of IL-1, IL-6, and TNF to the increased osteoclastogenesis induced by estrogen deficiency, ovariectomized (ovx) mice were treated with either IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1, TNF binding protein (TNFbp), an inhibitor of TNF, or the anti-IL-6 antibody (Ab) 20F3 for the first 2 wk after surgery. ovx increased the bone marrow cells secretion of IL-1 and TNF, but not IL-6, and the formation of TRAP-positive osteoclast-like multinucleated cells (MNCs) in bone marrow cultures treated with 1,25(OH)2D3. The increase in MNC formation induced by ovx was prevented by in vivo treatment with either 17 beta estradiol, IL-1ra, TNFbp, or anti-IL-6 Ab. However, the percent change in MNC formation induced by the anti-IL-6 Ab was similar in ovx and sham-operated animals, whereas IL-1ra and TNFbp were effective only in ovx mice. MNC formation was also decreased by in vitro treatment of bone marrow cultures with IL-1ra and TNFbp, but not with anti-IL-6 Ab. Ovx also increased bone resorption in vivo and in vitro, as assessed by the urinary excretion of pyridinoline cross links and the formation of resorption pits, respectively. IL-1ra, TNFbp and estrogen decreased bone resorption in vivo and in vitro whereas the anti-IL-6 Ab inhibited bone resorption in vitro but not in vivo. In conclusion, these data indicate that IL-1 and TNF play a direct role in mediating the effects of ovx on osteoclastogenesis and bone resorption. The data also suggest that IL-6 is not essential for increasing bone resorption in the early postovariectomy period. Images PMID:7989596

  13. Impacted maxillary canines and root resorptions of neighbouring teeth: a radiographic analysis using cone-beam computed tomography.

    PubMed

    Lai, Caroline S; Bornstein, Michael M; Mock, Lothar; Heuberger, Benjamin M; Dietrich, Thomas; Katsaros, Christos

    2013-08-01

    The study analyses the location of impacted maxillary canines and factors influencing root resorptions of adjacent teeth using cone-beam computed tomography (CBCT). In addition, the interrater reliability between observers of two different dental specialties for radiographic parameters will be evaluated. CBCT images of patients who were referred for radiographic localization of impacted maxillary canines and/or suspicion of root resorptions of adjacent teeth were included. The study analysed the exact three-dimensional location of the impacted canines in the anterior maxilla, frequency and extent of root resorptions, and potential influencing factors. To assess interrater agreement, Cohen's correlation parameters were calculated. This study comprises 113 patients with CBCT scans, and 134 impacted canines were analysed retrospectively. In the patients evaluated, 69 impacted canines were located palatally (51.49 per cent), 41 labially (30.60 per cent), and 24 (17.91 per cent) in the middle of the alveolar process. Root resorptions were found in 34 lateral incisors (25.37 per cent), 7 central incisors (5.22 per cent), 6 first premolars (4.48 per cent), and 1 second premolar (0.75 per cent). There was a significant correlation between root resorptions on adjacent teeth and localization of the impacted canine in relation to the bone, as well as vertical localization of the canine. Interrater agreement showed values of 0.546-0.877. CBCT provides accurate information about location of the impacted canine and prevalence and degree of root resorption of neighbouring teeth with high interrater correlation. This information is of great importance for surgeons and orthodontists for accurate diagnostics and interdisciplinary treatment planning.

  14. THE PARTICULATE HYDROLASES OF MACROPHAGES

    PubMed Central

    Cohn, Zanvil A.; Wiener, Edith

    1963-01-01

    The influence of phagocytosis on the morphological and biochemical properties of macrophage hydrolase-containing granules has been studied in vitro. Following the uptake of large numbers of heat-killed bacteria, an intracellular rearrangement of hydrolytic enzymes occurred. This was associated with the solubilization of 50 to 60 per cent of the total cell content of acid phosphatase, cathepsin, lysozyme, beta glucuronidase, acid ribonuclease, and acid desoxyribonuclease and with a corresponding decrease in granule-bound enzyme. With more prolonged incubation the majority of the soluble intracellular pool of acid ribonuclease and lysozyme was lost to the extracellular medium. No change in the total content of any of the hydrolases was noted during 180 minutes of incubation in vitro. The morphological fate of the granules was studied by a histochemical method for acid phosphatase. After the phagocytosis of yeast cell walls there was a disappearance of acid phosphatase-positive granules and an accumulation of reaction product about the ingested particle. Experiments employing macrophages which were supravitally stained with neutral red also demonstrated the loss of neutral red-positive granules and the accumulation of the dye about the yeast cell walls. These results strongly suggest that lysis of macrophage granules occurs following phagocytosis and that a portion of the granule contents are then resegregated within the newly formed phagocytic vacuole. PMID:14112262

  15. Macrophages in resistance to candidiasis.

    PubMed Central

    Vázquez-Torres, A; Balish, E

    1997-01-01

    Candida albicans, an increasingly common opportunistic pathogenic fungus, frequently causes disease in immunodeficient but not immunocompetent hosts. Clarifying the role of the phagocytic cells that participate in resistance to candidiasis not only is basic to understanding how the host copes with this dimorphic pathogen but also will expedite the development of innovative prophylactic and therapeutic approaches for treating the multiple clinical presentations that candidiasis encompasses. In this review, we present evidence that a diverse population of mononuclear phagocytes, in different states of activation and differentiation and from a variety of host species, can phagocytize C. albicans blastoconidia via an array of opsonic and nonopsonic mechanisms and can kill C. albicans blastoconidia and hyphae by means of oxygen-dependent and -independent mechanisms. Reactive nitrogen intermediates should now be added to the well-established candidacidal reactive oxygen intermediates of macrophages. Furthermore, what were thought to be two independent pathways, i.e., nitric oxide and superoxide anion, have now been shown to combine to form a potent macrophage candidacidal molecule, peroxynitrite. In contrast to monocytes and neutrophils, which are important in resistance to early stages of C. albicans infections, more differentiated macrophages activated by cytokines such as gamma interferon participate in the acquired resistance of hosts with C. albicans-specific, cell-mediated immunity. Evidence presented in this review demonstrates that mononuclear phagocytes, in some instances in the absence of other professional phagocytes such as neutrophils, play an import role in resistance to systemic and mucosal candidiasis. PMID:9184009

  16. A clinical evaluation of root resorption by formocresol treatment in 120 cases of pulpotomy in permanent molars.

    PubMed

    Hosseini, A A

    1992-01-01

    The effect of a formocresol pulpotomy of a 120 permanent molar showed external and internal resorption on distal root in lower molar, and palatal root in the upper molar. In this study 33.3% were male and 66.7% were female. The age distribution of patients was 16 to 20 years of age and 21 to 25 years of age. The rate of resorption for chronic pulpitis was more than acute pulpitis. The success of formocresol pulpotomy treatment at the end of the 10th year for acute pulpitis was 92.26% in contrast to 84% for chronic pulpitis. PMID:1290753

  17. [Vascularization and resorption of different supporting tissues by the greater omentum in the formation of compound microvascular transplants].

    PubMed

    Voy, E D

    1985-11-01

    In former investigations the author described the use of omentum majus in building microsurgical compound island flaps employing supporting tissue. Now different kinds of hard tissue, such as autogenous bone and cartilage, allogenous bone and cartilage (preserved by Cialit-solution), Teflon-Fluorocarbon Polymer (Proplast) and tri-calcium phosphate were presented in omentum-sandwich flaps in a histological investigation. We paid special attention to resorption and vascularisation of hard tissue. Allogenous cartilage grafts or artificial materials like Proplast were the most suitable to put into a compound omental island flap. There was good vascularisation with no resorption, especially with Proplast. PMID:2416640

  18. Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells

    SciTech Connect

    Islam, Shamima; Hassan, Ferdaus; Tumurkhuu, Gantsetseg; Dagvadorj, Jargalsaikhan; Koide, Naoki; Naiki, Yoshikazu; Mori, Isamu; Yoshida, Tomoaki; Yokochi, Takashi . E-mail: yokochi@aichi-med-u.ac.jp

    2007-08-24

    Lipopolysaccharide (LPS) is a potent bone resorbing factor. The effect of LPS on osteoclast formation was examined by using murine RAW 264.7 macrophage cells. LPS-induced the formation of multinucleated giant cells (MGC) in RAW 264.7 cells 3 days after the exposure. MGCs were positive for tartrate-resistant acid phosphatase (TRAP) activity. Further, MGC formed resorption pits on calcium-phosphate thin film that is a substrate for osteoclasts. Therefore, LPS was suggested to induce osteoclast formation in RAW 264.7 cells. LPS-induced osteoclast formation was abolished by anti-tumor necrosis factor (TNF)-{alpha} antibody, but not antibodies to macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-{kappa}B ligand (RANKL). TNF-{alpha} might play a critical role in LPS-induced osteoclast formation in RAW 264.7 cells. Inhibitors of NF-{kappa}B and stress activated protein kinase (SAPK/JNK) prevented the LPS-induced osteoclast formation. The detailed mechanism of LPS-induced osteoclast formation is discussed.

  19. A novel small-molecule PPI inhibitor targeting integrin αvβ3-osteopontin interface blocks bone resorption in vitro and prevents bone loss in mice.

    PubMed

    Park, Doori; Park, Chan-Won; Choi, YoungJin; Lin, Jingjing; Seo, Dong-Hyun; Kim, Han-Sung; Lee, Soo Young; Kang, In-Cheol

    2016-08-01

    Small molecule-inhibition targeting protein-protein interaction (PPI) is now recognized as an emerging and challenging area in drug design. We developed a novel interactive drug discovery methodology known as Protein Chip technology (ProteoChip) as a cutting-edge PPI assay system applicable for unique PPI-targeting therapeutics integrated with computer-aided drug design (CADD). Here, we describe a novel small molecular PPI inhibitor, IPS-02001, which the blocks integrin αvβ3-osteopontin interface a novel PPI inhibitor identified by the interactive methodology of both ProteoChip- and CADD-based PPI assay. IPS-02001 (6,7-Dichloro-2,3,5,8-tetrahydroxy-1,4-naphthoquinone) was screened from different compound libraries (InterBioScreen, Commercial libraries) using an in silico structure-based molecular docking simulation method and a protein chip-based protein-protein interaction assay system. Additionally, integrin αvβ3, an adhesion receptor expressed in osteoclasts (OCs), was implicated in the regulation of OC function via regulation of the cytoskeletal organization of OCs. IPS-02001 blocked OC maturation from murine bone marrow-derived macrophages, as well as the resorptive function of OCs. Moreover, treatment with IPS-02001 impaired downstream signaling of integrin αvβ3 linked to Pyk2, c-Src, PLCγ2, and Vav3 and disrupted the actin cytoskeleton in mature OCs. Furthermore, IPS-02001 blocked RANKL-induced bone destruction by reducing the number of OCs and protected against ovariectomy-induced bone loss in mice. Thus, IPS-02001 may represent a promising new class of anti-resorptive drugs for treatment of bone diseases associated with increased OC function. PMID:27187277

  20. Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis.

    PubMed

    Wisłowska, Margaret; Jakubicz, Danuta; Stepień, Krystyna; Cicha, Małgorzata

    2009-10-01

    Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-alpha, IL-1, IL-6) osteoclasts' activation, osteoprotegerin and its ligand's (RANKL) function disorders, patients' immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation--serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler-Rose's test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers' concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers' concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers' concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale's than at

  1. Dasatinib as a Bone-Modifying Agent: Anabolic and Anti-Resorptive Effects

    PubMed Central

    Garcia-Gomez, Antonio; Ocio, Enrique M.; Crusoe, Edvan; Santamaria, Carlos; Hernández-Campo, Pilar; Blanco, Juan F.; Sanchez-Guijo, Fermin M.; Hernández-Iglesias, Teresa; Briñón, Jesús G.; Fisac-Herrero, Rosa M.; Lee, Francis Y.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

    2012-01-01

    Background Bone loss, in malignant or non-malignant diseases, is caused by increased osteoclast resorption and/or reduced osteoblast bone formation, and is commonly associated with skeletal complications. Thus, there is a need to identify new agents capable of influencing bone remodeling. We aimed to further pre-clinically evaluate the effects of dasatinib (BMS-354825), a multitargeted tyrosine kinase inhibitor, on osteoblast and osteoclast differentiation and function. Methods For studies on osteoblasts, primary human bone marrow mensenchymal stem cells (hMSCs) together with the hMSC-TERT and the MG-63 cell lines were employed. Osteoclasts were generated from peripheral blood mononuclear cells (PBMC) of healthy volunteers. Skeletally-immature CD1 mice were used in the in vivo model. Results Dasatinib inhibited the platelet derived growth factor receptor-β (PDGFR-β), c-Src and c-Kit phosphorylation in hMSC-TERT and MG-63 cell lines, which was associated with decreased cell proliferation and activation of canonical Wnt signaling. Treatment of MSCs from healthy donors, but also from multiple myeloma patients with low doses of dasatinib (2–5 nM), promoted its osteogenic differentiation and matrix mineralization. The bone anabolic effect of dasatinib was also observed in vivo by targeting endogenous osteoprogenitors, as assessed by elevated serum levels of bone formation markers, and increased trabecular microarchitecture and number of osteoblast-like cells. By in vitro exposure of hemopoietic progenitors to a similar range of dasatinib concentrations (1–2 nM), novel biological sequelae relative to inhibition of osteoclast formation and resorptive function were identified, including F-actin ring disruption, reduced levels of c-Fos and of nuclear factor of activated T cells 1 (NFATc1) in the nucleus, together with lowered cathepsin K, αVβ3 integrin and CCR1 expression. Conclusions Low dasatinib concentrations show convergent bone anabolic and reduced bone

  2. Tissue-resident macrophages: then and now.

    PubMed

    Davies, Luke C; Taylor, Philip R

    2015-04-01

    Macrophages have been at the heart of immune research for over a century and are an integral component of innate immunity. Macrophages are often viewed as terminally differentiated monocytic phagocytes. They infiltrate tissues during inflammation, and form polarized populations that perform pro-inflammatory or anti-inflammatory functions. Tissue-resident macrophages were regarded as differentiated monocytes, which seed the tissues to perform immune sentinel and homeostatic functions. However, tissue-resident macrophages are not a homogeneous population, but are in fact a grouping of cells with similar functions and phenotypes. In the last decade, it has been revealed that many of these cells are not terminally differentiated and, in most cases, are not derived from haematopoiesis in the adult. Recent research has highlighted that tissue-resident macrophages cannot be grouped into simple polarized categories, especially in vivo, when they are exposed to complex signalling events. It has now been demonstrated that the tissue environment itself is a major controller of macrophage phenotype, and can influence the expression of many genes regardless of origin. This is consistent with the concept that cells within different tissues have diverse responses in inflammation. There is still a mountain to climb in the field, as it evolves to encompass not only tissue-resident macrophage diversity, but also categorization of specific tissue environments and the plasticity of macrophages themselves. This knowledge provides a new perspective on therapeutic strategies, as macrophage subsets can potentially be manipulated to control the inflammatory environment in a tissue-specific manner. PMID:25684236

  3. Development and maintainance of resident macrophages

    PubMed Central

    Perdiguero, Elisa Gomez; Geissmann, Frederic

    2016-01-01

    The molecular and cellular mechanisms that underlie the many roles of macrophages in health and disease states in vivo remain poorly understood. The purpose of this Review is to present and discuss current knowledge on the developmental biology of macrophages, as it underlies the concept of a layered myeloid system composed of ‘resident’ macrophages that mostly originate from yolk sac progenitors and of ‘passenger’ or ‘transitory’ myeloid cells that originate and renew from bone marrow hematopoietic stem cells, and to provide a framework to investigate the functions of macrophages in vivo. PMID:26681456

  4. Collagenase Production by Endotoxin-Activated Macrophages

    PubMed Central

    Wahl, Larry M.; Wahl, Sharon M.; Mergenhagen, Stephan E.; Martin, George R.

    1974-01-01

    Peritoneal exudate macrophages, when exposed to bacterial lipopolysaccharide in culture, were found to produce collagenase (EC 3.4.24.3). This enzyme was not detected in extracts of the macrophages or in media from nonstimulated macrophage cultures. Lipidcontaining fractions of the lipopolysaccharide, including a glycolipid from the rough mutant of Salmonella minnesota (R595) and lipid A, were potent stimulators of collagenase production. The lipid-free polysaccharide fraction had no effect. Cycloheximide prevented the production of collagenase by endotoxin-treated macrophages, suggesting that it was newly synthesized. Images PMID:4372628

  5. The role of interleukin-1 in bone resorption in rheumatoid arthritis.

    PubMed

    Strand, V; Kavanaugh, A F

    2004-06-01

    Bone loss in RA includes juxta-articular osteopenia, erosions and systemic osteoporosis. In each case, synthesis of new bone matrix is unable to balance osteoclast-mediated bone resorption, resulting in net bone loss. IL-1, TNF and other proinflammatory cytokines stimulate osteoclast differentiation and activation, resulting in bone loss. In addition, these proinflammatory cytokines stimulate synovial fibroblasts and chondrocytes to produce proteinases that degrade cartilage. In animal arthritis models, blocking IL-1 significantly reduces bone erosions and cartilage degradation, whereas blocking TNF decreases synovitis. In patients with active RA, treatment with the TNF blockers etanercept and infliximab, as well as with anakinra, a recombinant human IL-1 receptor antagonist, significantly reduced erosions and joint space narrowing. It remains to be determined, however, whether slowing radiographic progression with these biological therapies will significantly improve long-term outcomes in RA.

  6. Age-related bone resorption in the normal incus: a case of maladaptive remodelling?

    PubMed Central

    Lannigan, F J; O'Higgins, P; Oxnard, C E; McPhie, P

    1995-01-01

    The changes that occur in the normal human incus with age have been investigated. Evidence for age-related changes in this ossicle, especially in the region of the long process, has been accumulating over the last 30-40 years and yet they have neither been confirmed quantitatively nor explained satisfactorily. In this study the results of a morphometric study of the long processes of a series of normal incudes are presented. These demonstrate that the lenticular and long processes undergo progressive symmetric resorption with advancing age. We consider these findings in the light of previous considerations of incudal remodelling and propose that these remodelling changes may reflect a normal adaptive response to the biomechanical milieu of the human middle ear. PMID:7559138

  7. Pre-eruptive intra-coronal resorption: controversies and treatment options.

    PubMed

    Spierer, Weil Ayala; Fuks, Anna B

    2014-01-01

    Pre-eruptive intra-coronal resorption (PIER) is a defect located in the dentin of an unerupted tooth, just beneath the dentin-enamel junction, with a prevalence of 0.5-2% of the teeth. The depth of the lesion is variable and may also reach the pulp. In the past, these lesions were confused with caries, and were therefore called "hidden" or "pre-eruptive caries". These defects are usually detected incidentally in routine dental radiographs. It has been proven that in the pre-eruptive stage the lesions contain soft tissue and inflammatory cells. The present report describes the clinical management of a case of PEIR on a mandibular first permanent molar and discusses the alternatives for treatment.

  8. Genetic predisposition to external apical root resorption in orthodontic patients: linkage of chromosome-18 marker.

    PubMed

    Al-Qawasmi, R A; Hartsfield, J K; Everett, E T; Flury, L; Liu, L; Foroud, T M; Macri, J V; Roberts, W E

    2003-05-01

    External apical root resorption (EARR) is a common orthodontic treatment sequela. Previous studies implicate a substantial genetic component for EARR. Using a candidate gene approach, we investigated possible linkage of EARR associated with orthodontic treatment with the TNSALP, TNFalpha, and TNFRSF11A gene loci. The sample was comprised of 38 American Caucasian families with a total of 79 siblings who completed comprehensive orthodontic treatment. EARR was assessed by means of pre- and post-treatment radiographs. Buccal swab cells were collected for extraction and analysis of DNA. No evidence of linkage was found with EARR and the TNFalpha and TNSALP genes. Non-parametric sibling pair linkage analysis identified evidence of linkage (LOD = 2.5; p = 0.02) of EARR affecting the maxillary central incisor with the microsatellite marker D18S64 (tightly linked to TNFRSF11A). This indicates that the TNFRSF11A locus, or another tightly linked gene, is associated with EARR.

  9. Calcium-41 as a long-term biological tracer for bone resorption

    NASA Astrophysics Data System (ADS)

    Elmore, David; Bhattacharyya, Maryka H.; Sacco-Gibson, Nancy; Peterson, David P.

    1990-12-01

    The use of 41Ca (half-life 1 × 10 5 yr) as a tracer for studying calcium metabolism in living systems is compared to the shorter-lived radionuclides 45Ca (165 d) and 47Ca (45 d) and the stable isotopes 42Ca and 44Ca. The feasibility of using accelerator mass spectrometry (AMS) measurements of 41Ca for studying multi-year calcium resorption in humans was tested as part of a companion study that used 45Ca to measure the effects of dietary cadmium on calcium metabolism in dogs. It was shown that Ca resorbed from prelabeled bones correlates well with 45Ca for a period of 28 weeks. The advantage of 41Ca is that, even with a negligible radiation dose, it can be measured by AMS long after the 45Ca becomes unmeasurable.

  10. Multidisciplinary approach for the treatment of extensive external cervical resorption after dental trauma.

    PubMed

    Alves, T P; Soares, T R C; Barreto, S C; Fried, H; Pereira, G D S; Maia, L C; Santos, A E C

    2013-01-01

    External cervical resorption (ECR) is a sequela of dentoalveolar trauma that may cause functional, esthetic, and psychologic alterations. The aim of this study was to report a successful multidisciplinary treatment approach performed in a 12-year-old patient who presented with posttraumatic ECR associated with extensive opened cavity, pulp necrosis, and periapical lesion of tooth number 9, with an initial unfavorable prognosis. Crown lengthening was done to enable restoration of vestibular surface with resin composite, forming a barrier that allowed endodontic treatment. Afterwards, a prefabricated fiberglass post was cemented and esthetic restoration was performed using the adhesive technique and direct composite veneer. Reconstructive periodontal surgery was performed to correct irregular gingival contour. After treatment and successive follow-up sessions, it was concluded that although the tooth had been indicated for extraction, low invasive direct techniques were effective to recover function and esthetics and to maintain the tooth in the oral cavity. PMID:23210917

  11. Doxycycline inhibits bone resorption by human interface membrane cells from aseptically loose hip replacements.

    PubMed

    Ong, S M; Taylor, G J S

    2003-04-01

    Matrix metalloproteinases (MMPs) may have a role in the process of aseptic loosening. Doxycycline has been shown to inhibit MMPs. Our aim was to investigate the potential pharmacological effect of doxycycline on aseptic loosening. We used radiolabelled mouse calvariae cultured with human interface membrane cells from aseptically loosened hips. Bone resorption was confirmed in this model. The effect of doxycycline was assessed by culturing dead radiolabelled bone discs with cells from the interface membrane with doxycycline. The control group consisted of the same culture system without doxycycline. Supernatant 45calcium and the total 45calcium remaining in the bone discs at the completion of the culture were used to measure osteolysis. We found that doxycycline can inhibit osteolysis at the interface membrane of aseptically loosened hips. This may have therapeutic implications for the treatment of patients with aseptic loosening of total joint replacements. PMID:12729128

  12. Role of serum FSH measurement on bone resorption in postmenopausal women.

    PubMed

    García-Martín, Antonia; Reyes-García, Rebeca; García-Castro, José Miguel; Rozas-Moreno, Pedro; Escobar-Jiménez, Fernando; Muñoz-Torres, Manuel

    2012-04-01

    In vitro and animals models have shown follicle-stimulating hormone (FSH) effects on osteoclastic function, and FSH levels seem to influence bone loss independently of estrogen concentrations in humans. Our aim was to evaluate the role of serum FSH measurement in the assessment of bone resorption in postmenopausal women. We conducted a cross-sectional study including 92 postmenopausal healthy women aged 56.2 (3.6) and 7.2 (4) years since menopause. Serum FSH, luteinizing hormone (LH), estradiol (E2) and bone turnover markers as osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) were measured. We analyzed the relationship between serum levels of gonadotropins, E2, and bone turnover markers. Serum levels of OC and CTX were positively related to FSH (r = 0.234, P = 0.047 and r = 0.384, P = 0.003) and LH (r = 0.319, P = 0.012 and r = 0.273, P = 0.038). There was no relationship with E2 levels. When gonadotropins levels were divided into quartiles, we found significant differences in bone turnover markers between the first and the fourth quartile. OC levels were higher in the highest quartile of FSH (P = 0.024) and LH (P = 0.001). Serum CTX was also higher in the highest quartile of FSH (P = 0.004) and LH (P = 0.039). FSH levels could explain approximately 14.7% of the chances in CTX. In summary, gonadotropins were related to bone turnover in postmenopausal healthy women. Moreover, the rise in FSH appears to contribute to higher bone resorption. Our results suggest that the measurement of FSH could be usefulness to perform a more comprehensive assessment of bone loss in these women.

  13. Apoptosis-associated uncoupling of bone formation and resorption in osteomyelitis

    PubMed Central

    Marriott, Ian

    2013-01-01

    The mechanisms underlying the destruction of bone tissue in osteomyelitis are only now being elucidated. While some of the tissue damage associated with osteomyelitis likely results from the direct actions of bacteria and infiltrating leukocytes, perhaps exacerbated by bacterial manipulation of leukocyte survival pathways, infection-induced bone loss predominantly results from an uncoupling of the activities of osteoblasts and osteoclasts. Bacteria or their products can directly increase osteoclast formation and activity, and the inflammatory milieu at sites of infection can further promote bone resorption. In addition, osteoclast activity is critically regulated by osteoblasts that can respond to bacterial pathogens and foster both inflammation and osteoclastogenesis. Importantly, bone loss during osteomyelitis is also brought about by a decline in new bone deposition due to decreased bone matrix synthesis and by increased rates of osteoblast apoptosis. Extracellular bacterial components may be sufficient to reduce osteoblast viability, but the causative agents of osteomyelitis are also capable of inducing continuous apoptosis of these cells by activating intrinsic and extrinsic cell death pathways to further uncouple bone formation and resorption. Interestingly, bacterial internalization appears to be required for maximal osteoblast apoptosis, and cytosolic inflammasome activation may act in concert with autocrine/paracrine death receptor-ligand signaling to induce cell death. The manipulation of apoptotic pathways in infected bone cells could be an attractive new means to limit inflammatory damage in osteomyelitis. However, the mechanism that is the most important in bacterium-induced bone loss has not yet been identified. Furthermore, it remains to be determined whether the host would be best served by preventing osteoblast cell death or by promoting apoptosis in infected cells. PMID:24392356

  14. In vitro osteoclast formation and resorption of silicon-substituted hydroxyapatite ceramics.

    PubMed

    Friederichs, Robert J; Brooks, Roger A; Ueda, Masato; Best, Serena M

    2015-10-01

    Materials that participate in bone remodeling at the implant/tissue interface represent a modern tissue engineering approach with the aim of balancing implant resorption and nascent tissue formation. Silicon-substituted hydroxyapatite (SiHA) ceramics are capable of stimulating new bone formation, but little is known about their interaction with osteoclasts (OC). The effects of soluble silicate and SiHA on OCs were investigated in this study. Soluble silicate below 500 μM did not stimulate cell metabolism at 4 days or alter resorption area at 7 days on calcium phosphate discs. On sintered ceramics, OC numbers were similar on HA, Si0.3 HA (0.5 wt % Si) and Si0.5 HA (1.2 wt % Si) after 21 days in vitro, but actin ring sealing zone morphology on SiHA resembled that commonly found on bone or on carbonate-substituted hydroxyapatite (CHA). Smaller and thicker actin rings on SiHA as compared to HA were probably the result of altered surface chemistry and solubility differences. The more stable sealing zones and increased lattice solubility likely contributed to increased individual pit volumes observed on Si0.5 HA. The delayed formation of OCs on Si0.5 HA (lower numbers at day 14) excludes earlier differentiation as a possible mechanism of increased individual OC pit volumes at later times (day 21). Materials characterization of Si containing biomaterials remains paramount as the Si type and amounts can subsequently impact downstream OC behaviour in a complex manner. PMID:25847383

  15. In vitro osteoclast formation and resorption of silicon-substituted hydroxyapatite ceramics.

    PubMed

    Friederichs, Robert J; Brooks, Roger A; Ueda, Masato; Best, Serena M

    2015-10-01

    Materials that participate in bone remodeling at the implant/tissue interface represent a modern tissue engineering approach with the aim of balancing implant resorption and nascent tissue formation. Silicon-substituted hydroxyapatite (SiHA) ceramics are capable of stimulating new bone formation, but little is known about their interaction with osteoclasts (OC). The effects of soluble silicate and SiHA on OCs were investigated in this study. Soluble silicate below 500 μM did not stimulate cell metabolism at 4 days or alter resorption area at 7 days on calcium phosphate discs. On sintered ceramics, OC numbers were similar on HA, Si0.3 HA (0.5 wt % Si) and Si0.5 HA (1.2 wt % Si) after 21 days in vitro, but actin ring sealing zone morphology on SiHA resembled that commonly found on bone or on carbonate-substituted hydroxyapatite (CHA). Smaller and thicker actin rings on SiHA as compared to HA were probably the result of altered surface chemistry and solubility differences. The more stable sealing zones and increased lattice solubility likely contributed to increased individual pit volumes observed on Si0.5 HA. The delayed formation of OCs on Si0.5 HA (lower numbers at day 14) excludes earlier differentiation as a possible mechanism of increased individual OC pit volumes at later times (day 21). Materials characterization of Si containing biomaterials remains paramount as the Si type and amounts can subsequently impact downstream OC behaviour in a complex manner.

  16. ADRA2A is involved in neuro-endocrine regulation of bone resorption

    PubMed Central

    Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

    2015-01-01

    Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

  17. MAPK11 in breast cancer cells enhances osteoclastogenesis and bone resorption

    PubMed Central

    He, Zhimin; He, Jin; Liu, Zhiqiang; Xu, Jingda; Yi, Sofia F.; Liu, Huan; Yang, Jing

    2014-01-01

    Breast cancer cells frequently metastasize to bone and induce osteolytic bone destruction in patients. These metastases cause severe bone pain, high risk of fractures and hypercalcemia, and are essentially incurable and fatal. Recent studies show that breast cancer cells in bone activate osteoclastogenesis and bone resorption. However the underlying mechanism is poorly understood. This study shows that the p38 MAPK (p38) isoform MAPK11 (p38β) is expressed in breast cancer cells. By using specific small hairpin RNAs for MAPK11, we demonstrated that p38β-mediated p38 activity in breast cancer cells is responsible for breast cancer-induced osteolytic bone destruction. The addition of conditioned media from breast cancer cell lines MDA-MB-231 and MDA-MB-468, which have high expression of p38β, induced osteoclast differentiation and bone resorption. In contrast, knockdown of p38β in breast cancer cells reduced osteoclast differentiation in vitro and reduced bone destruction in severe combined immunodeficiency (SCID) mouse models. The knockdown of p38β did not affect tumor growth or survival or the ability of cancer cells to home to bone. Furthermore, our results showed that p38β upregulated the expression and secretion of monocyte chemotactic protein-1 (MCP-1) in breast cancer cells, and upregulated MCP-1 activates osteoclast differentiation and activity. This study elucidates a novel molecular mechanism of breast cancer cell-induced osteolytic bone destruction. This study also indicates that targeting breast cancer cell p38β and its product MCP-1 may be a viable approach to treat or prevent bone destruction in patients with bone-metastatic breast cancer. PMID:25066918

  18. The effect of fluoride on the resorption of dentine by osteoclasts in vitro.

    PubMed

    Taylor, M L; Maconnachie, E; Frank, K; Boyde, A; Jones, S J

    1990-03-01

    Osteoclasts were isolated mechanically from bones of prehatch chicks and cultured on dentine for 24 or 39 h in medium without or with added sodium fluoride at concentrations of 0.15, 1, 15, or 30 mg/liter. Fixed and toluidine blue-stained specimens were examined by light microscopy and osteoclasts were counted, all cells were removed and resorption pits were counted. The dentine was then prepared for scanning electron microscopy (SEM) and pits located on a raster search using backscattered electron imaging. Stereophotogrammetric measurements were made of the depths, plan and true surface areas and volumes of pits, and the volume:area ratio and a three-dimensional form factor calculated for each. The presence or absence of a ring of demineralization around each pit was recorded. Pits with the same plan area were significantly (p less than 0.001) less deep in cultures containing 15 or 30 mg/liter NaF and the incidence of rings around pits was higher (controls 2.7%, 15 mg/liter 31.3%, 30 mg/liter NaF 39.7%). In one experiment, pits were larger in the specimen cultured with added 1 mg/liter NaF, but in a much larger series of 631 (251 in the control and 380 in the 1 mg/liter NaF cultures) pits measured, depths, volumes and volume:plan-area ratios were significantly lower (p less than 0.001), and rings round pits 2.5 times more common, in the fluoride-treated group. A complex interplay of stimulation of some cells in the culture with indirect stimulation of osteoclasts and direct inhibition of osteoclastic resorptive function may be operating at this concentration of fluoride. In vivo, therapeutic doses of sodium fluoride would be expected to act not only to increase the formation of osteoid but also to suppress osteoclastic activity.

  19. Osteoclast resorption of thermal spray hydoxyapatite coatings is influenced by surface topography.

    PubMed

    Gross, Karlis A; Muller, Dirk; Lucas, Helen; Haynes, David R

    2012-05-01

    Coating characteristics such as composition, crystallite features and topography collectively impact the cell response. The influence from splats has not yet been assessed for hydroxyapatite (HAp) thermal spray coatings. The objective of this work is to (a) survey the topography on commercial implants, (b) ascertain topography formation from single splats, and (c) determine the osteoclast resorption pattern on a topographically refined coating compared to dentine. Coatings on dental implants, an orthopedic screw, a femoral stem and a knee implant were studied for reference. The effects of substrate pre-heat, roughness, spray distance and particle size on the coating roughness and topography were studied. Human-derived osteoclasts were placed on a coating with refined topography and compared to dentine, a polished coating and polished sintered HAp. A pre-heat of at least 200°C on titanium was required to form rounded splats. The greatest influence on coating roughness and topography arose from particle size. A 2-fold increase in the mean particle size from 30 to 72 μm produced a significant difference (P<0.001) in roughness from 4.8 and 9.7 μm. A model is shown to illustrate topography formation, nanostructure evolution on single splats, and the topography as seen in commercial implants. Osteoclasts showed a clear preference for activity on coatings with refined topography. A one-way ANOVA test revealed a significantly greater pit depth (P=0.022) for dentine (14 μm) compared to the as-sprayed and polished coating (5 μm). Coatings with topography display a similar number of resorption pits with dentine, but a 10-fold greater number than polished coatings, emphasizing the importance of flattened droplet topography on implant surfaces.

  20. Isotopic evidence for resorption of soft tissues and bone in immobilized dogs

    SciTech Connect

    Klein, L.; Player, J.S.; Heiple, K.G.; Bahniuk, E.; Goldberg, V.M.

    1982-02-01

    Various experimental methods for producing bone and ligament atrophy have yielded contradictory results. These methods include denervation, immobilization (both internal and external), and disarticulation. We studied a model of internal skeletal fixation for twelve weeks in dogs that were chronically prelabeled with 3H-tetracycline, 45Ca, and 3H-proline. Bone resorption was analyzed by the loss of 3H-tetracycline, and bone and soft-tissue mass were analyzed by the radiochemical and chemical analysis of calcium and collagen. The strength of the anterior cruciate ligament was studied in tension to failure when a fast rate of deformation was applied. Failure of the femur-ligament-tibia complex occurred through the insertion of the ligament into the tibia for both the experimental and the control limbs. Loss of collagen was greater in the tibia and femur than in the lateral meniscus and anterior cruciate ligament, and correlated with a mechanical failure via bone. No evidence for collagen replacement in atrophied tissues was found, but one-half of the resorbed calcium was conserved. The marked loss of 3H-tetracycline indicated that bone atrophy was the result of increased resorption of bone rather than decreased bone formation. Clinical Relevance: We have demonstrated significant atrophy of the soft tissues (lateral meniscus and anterior cruciate ligament) as well as of bone in immobilized joints of dogs. It is likely that the decrease in strength of the bone-ligament-bone complex is related to this atrophy of soft tissues and bone around the joint.

  1. Inhibited osteoblastogenesis, enhanced bone resorption and disrupted vitamin d3 homeostasis in female c57bl/6 mice fed alcohol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Alcohol abuse is a well-known factor for increased risk of osteoporosis. Previous studies have shown that molecular mechanisms underlying alcohol-induced bone loss are complex, involving direct effects on both bone formation and resorption and additional indirect actions via endocrine disruption. Wh...

  2. Nutrient resorption helps drive intra-specific coupling of foliar nitrogen and phosphorus under nutrient-enriched conditions

    USGS Publications Warehouse

    Xiao-Tao, Lü; Reed, Sasha C.; Yu, Qiang; Han, Xing-Guo

    2016-01-01

    Taken together, the results suggest plants in this ecosystem are much more responsive to changing N cycles than P cycles and emphasize the significance of nutrient resorption as an important plant control over the stoichiometric coupling of N and P under nutrient enriched conditions.

  3. Fresh-frozen human bone allograft in vertical ridge augmentation: clinical and tomographic evaluation of bone formation and resorption.

    PubMed

    Macedo, Luis Guilherme Scavone; Mazzucchelli-Cosmo, Luiz Antonio; Macedo, Nelson Luiz; Monteiro, Adriana Socorro Ferreira; Sendyk, Wilson Roberto

    2012-12-01

    The aim of the current study is to evaluate fresh-frozen human bone allografts (FHBAs) used in vertical ridge augmentation clinically and by computed tomography, and to analyze the resulting bone formation and graft resorption. Sixteen FHBAs were grafted in the maxillae and mandibles of 9 patients. The FHBAs, which were provided by the Musculoskeletal Tissue Bank of Marilia Hospital (Unioss), were frozen at -80°C. After 7 months, dental implants were placed and bone parameters were evaluated. Vertical bone formation was measured by computerized tomography before (T0) and at 7 months (T1) after the surgical procedure. Bone graft resorption was measured clinically from a landmark screw head using a periodontal probe. The results were analyzed by Student's t-test. Significant differences existed in the bone formation values at T0 and T1, with an average change of 4.03 ± 1.69 mm. Bone graft resorption values were 1.0 ± 0.82 mm (20%). Implants were placed with varying insertion torque values (35-45 Ncm), and achieved primary stability. This study demonstrates that FHBAs promote satisfactory vertical bone formation with a low resorption rates, good density, and primary implant stability. PMID:21811779

  4. 3H-tetracycline as a proxy for 41Ca for measuring dietary perturbations of bone resorption

    NASA Astrophysics Data System (ADS)

    Weaver, Connie; Cheong, Jennifer; Jackson, George; Elmore, David; McCabe, George; Martin, Berdine

    2007-06-01

    Our group is interested in evaluating early effects of dietary interventions on bone loss. Postmenopausal women lose bone following reduction in estrogen which leads to increased risk of fracture. Traditional means of monitoring bone loss and effectiveness of treatments include changes in bone density, which takes 6 months to years to observe effects, and changes in biochemical markers of bone turnover, which are highly variable and lack specificity. Prelabeling bone with 41Ca and measuring urinary 41Ca excretion with accelerator mass spectrometry provides a sensitive, specific, and rapid approach to evaluating effectiveness of treatment. To better understand 41Ca technology as a tool for measuring effective treatments on reducing bone resorption, we perturbed bone resorption by manipulating dietary calcium in rats. We used 3H-tetracycline (3H-TC) as a proxy for 41Ca and found that a single dose is feasible to study bone resorption. Suppression of bone resorption, as measured by urinary 3H-TC, by dietary calcium was observed in rats stabilized after ovariectomy, but not in recently ovariectomized rats.

  5. Targeted overexpression of osteoactivin in cells of osteoclastic lineage promotes osteoclastic resorption and bone loss in mice.

    PubMed

    Sheng, Matilda H-C; Wergedal, Jon E; Mohan, Subburaman; Amoui, Mehran; Baylink, David J; Lau, K-H William

    2012-01-01

    This study sought to test whether targeted overexpression of osteoactivin (OA) in cells of osteoclastic lineage, using the tartrate-resistant acid phosphase (TRAP) exon 1B/C promoter to drive OA expression, would increase bone resorption and bone loss in vivo. OA transgenic osteoclasts showed ∼2-fold increases in OA mRNA and proteins compared wild-type (WT) osteoclasts. However, the OA expression in transgenic osteoblasts was not different. At 4, 8, and 15.3 week-old, transgenic mice showed significant bone loss determined by pQCT and confirmed by μ-CT. In vitro, transgenic osteoclasts were twice as large, had twice as much TRAP activity, resorbed twice as much bone matrix, and expressed twice as much osteoclastic genes (MMP9, calciton receptor, and ADAM12), as WT osteoclasts. The siRNA-mediated suppression of OA expression in RAW264.7-derived osteoclasts reduced cell size and osteoclastic gene expression. Bone histomorphometry revealed that transgenic mice had more osteoclasts and osteoclast surface. Plasma c-telopeptide (a resorption biomarker) measurements confirmed an increase in bone resorption in transgenic mice in vivo. In contrast, histomorphometric bone formation parameters and plasma levels of bone formation biomarkers (osteocalcin and pro-collagen type I N-terminal peptide) were not different between transgenic mice and WT littermates, indicating the lack of bone formation effects. In conclusion, this study provides compelling in vivo evidence that osteoclast-derived OA is a novel stimulator of osteoclast activity and bone resorption.

  6. Interleukin 6 production in fetal rat long bone cultures is correlated with PGE2 release and does not correlate with the extent of bone resorption.

    PubMed

    Bertolini, D R; Votta, B; Hoffman, S; Strassmann, G

    1994-07-01

    Reports from several laboratories have suggested that interleukin 6 (IL-6) may play a role in the process of bone resorption. We have extended these studies by examining the role of IL-6 in fetal rat long bone (FRLB) resorption stimulated by a variety of agents, including parathyroid hormone (PTH); 1,25 dihydroxyvitamin D3 (1,25(OH)2D3); interleukin 1 (IL-1); tumour necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS). This model of bone resorption does not require the generation of osteoclasts in order to elicit a resorptive response and allowed us to assess whether IL-6 can directly affect osteoclastic bone resorption. We confirmed previous studies which showed that exogenous recombinant murine or human IL-6 does not stimulate bone resorption and demonstrated that IL-6, when added prior to the addition of parathyroid hormone, caused a significant but somewhat variable inhibition at 120 hours. Exogenous PGE2 stimulated both IL-6 production and resorption in FRLB cultures in a concentration-dependent manner. Endogenous production of IL-6 in fetal rat long bone (FRLB) cultures was stimulus dependent and generally correlated with prostaglandin E2 (PGE2) levels in the same cultures. However, endogenous IL-6 production did not correlate with the extent of bone resorption, except when IL-1 and PGE2 were used as stimuli. Addition of indomethacin and diclofenac to IL-1 stimulated cultures demonstrated that both the IL-6 production and bone resorption were largely PGE-2 dependent. Neutralizing anti-IL-6 antibodies inhibited IL-6 activity in FRLB cultures but did not affect bone resorption, even in the IL-1 stimulated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Warming and drought differentially influence the production and resorption of elemental and metabolic nitrogen pools in Quercus rubra.

    PubMed

    Suseela, Vidya; Tharayil, Nishanth; Xing, Baoshan; Dukes, Jeffrey S

    2015-11-01

    The process of nutrient retranslocation from plant leaves during senescence subsequently affects both plant growth and soil nutrient cycling; changes in either of these could potentially feed back to climate change. Although elemental nutrient resorption has been shown to respond modestly to temperature and precipitation, we know remarkably little about the influence of increasing intensities of drought and warming on the resorption of different classes of plant metabolites. We studied the effect of warming and altered precipitation on the production and resorption of metabolites in Quercus rubra. The combination of warming and drought produced a higher abundance of compounds that can help to mitigate climatic stress by functioning as osmoregulators and antioxidants, including important intermediaries of the tricarboxylic acid (TCA) cycle, amino acids including proline and citrulline, and polyamines such as putrescine. Resorption efficiencies (REs) of extractable metabolites surprisingly had opposite responses to drought and warming; drought treatments generally increased RE of metabolites compared to ambient and wet treatments, while warming decreased RE. However, RE of total N differed markedly from that of extractable metabolites such as amino acids; for instance, droughted plants resorbed a smaller fraction of elemental N from their leaves than plants exposed to the ambient control. In contrast, plants in drought treatment resorbed amino acids more efficiently (>90%) than those in ambient (65-77%) or wet (42-58%) treatments. Across the climate treatments, the RE of elemental N correlated negatively with tissue tannin concentration, indicating that polyphenols produced in leaves under climatic stress could interfere with N resorption. Thus, senesced leaves from drier conditions might have a lower nutritive value to soil heterotrophs during the initial stages of litter decomposition despite a higher elemental N content of these tissues. Our results suggest that N

  8. Thinning affects nutrient resorption and nutrient-use efficiency in two Pinus sylvestris stands in the Pyrenees.

    PubMed

    Blanco, Juan A; Imbert, J Bosco; Castillo, Federico J

    2009-04-01

    Needle chemical composition was measured, and nutrient resorption, nutrient-use efficiency (NUE), and other indexes were estimated for 24 months in two contrasting natural Pinus sylvestris L. forests in the western Pyrenees in Spain. For each location (Aspurz, 650 m elevation, 7% slope; Garde, 1335 m elevation, 40% slope), there were three reference plots (P0), three plots with 20% of the basal area removed (P20), and three with 30% of the basal area removed (P30). Needle P, Ca, and Mg concentrations were higher in Garde, but N concentration was higher for Aspurz, without differences for K. Nutrient-resorption efficiency of P was higher in Aspurz, of Mg higher in Garde, and there were no differences between sites in N and K. Nutrient-resorption proficiency was significantly higher in the site with lower soil nutrient availability, i.e., for P, Ca, and Mg in Aspurz, but N in Garde (no differences in K); this may be an indicator of nutrient conservation strategy. Annual nutrient productivity (A) was higher for all nutrients in Aspurz, whereas the mean residence time (MRT) was higher in Garde in all nutrients but P. NUE was significantly higher in Garde for all nutrients but P, which was more efficiently used in Aspurz. In both sites, N, P, and K concentrations were higher in the 2002 cohort, Ca in the 2000 cohort, and maximum Mg was found in the 2001 cohort. Thinning caused a reduction of Mg concentration in the 2001 cohort in Aspurz, an increase of Ca resorption proficiency in Aspurz and Mg resorption at both sites, and reduction of P, K, and Mg nutrient response efficiency (NRE) in Garde. Thinning may have caused an increase of the C:Mg ratio through facilitating the development of more biosynthesis apparatus in a more illuminated canopy, but it seemed not to affect resorption in a significant way. Changes in NRE in Garde after thinning show that forest management can affect how trees use nutrients. Our results indicate that the strategy to optimize NUE is

  9. From histology to micro-CT: Measuring and modeling resorption cavities and their relation to bone competence

    PubMed Central

    Vanderoost, Jef; van Lenthe, G Harry

    2014-01-01

    The process of bone remodelling plays an essential role in the emergence and maintenance of bone geometry and its internal structure. Osteoclasts are one of the three main bone cell types that play a crucial role in the bone remodelling cycle. At the microstructural level, osteoclasts create bone deficits by eroding resorption cavities. Understanding how these cavities impair the mechanical quality of the bone is not only relevant in quantifying the impact of resorption cavities in healthy bone and normal aging, but maybe even more so in quantifying their role in metabolic bone diseases. Metabolic bone diseases and their treatment are both known to affect the bone remodelling cycle; hence, the bone mechanical competence can and will be affected. However, the current knowledge of the precise dimensions of these cavities and their effect on bone competence is rather limited. This is not surprising considering the difficulties in deriving three-dimensional (3D) properties from two-dimensional (2D) histological sections. The measurement difficulties are reflected in the evaluation of how resorption cavities affect bone competence. Although detailed 3D models are generally being used to quantify the mechanical impact of the cavities, the representation of the cavities themselves has basically been limited to simplified shapes and averaged cavity properties. Qualitatively, these models indicate that cavity size and location are important, and that the effect of cavities is larger than can be expected from simple bone loss. In summary, the dimensions of osteoclast resorption cavities were until recently estimated from 2D measures; hence, a careful interpretation of resorption cavity dimensions is necessary. More effort needs to go into correctly quantifying resorption cavities using modern 3D imaging techniques like micro-computed tomography (micro-CT) and synchrotron radiation CT. Osteoclast resorption cavities affect bone competence. The structure-function relationships

  10. Warming and drought differentially influence the production and resorption of elemental and metabolic nitrogen pools in Quercus rubra.

    PubMed

    Suseela, Vidya; Tharayil, Nishanth; Xing, Baoshan; Dukes, Jeffrey S

    2015-11-01

    The process of nutrient retranslocation from plant leaves during senescence subsequently affects both plant growth and soil nutrient cycling; changes in either of these could potentially feed back to climate change. Although elemental nutrient resorption has been shown to respond modestly to temperature and precipitation, we know remarkably little about the influence of increasing intensities of drought and warming on the resorption of different classes of plant metabolites. We studied the effect of warming and altered precipitation on the production and resorption of metabolites in Quercus rubra. The combination of warming and drought produced a higher abundance of compounds that can help to mitigate climatic stress by functioning as osmoregulators and antioxidants, including important intermediaries of the tricarboxylic acid (TCA) cycle, amino acids including proline and citrulline, and polyamines such as putrescine. Resorption efficiencies (REs) of extractable metabolites surprisingly had opposite responses to drought and warming; drought treatments generally increased RE of metabolites compared to ambient and wet treatments, while warming decreased RE. However, RE of total N differed markedly from that of extractable metabolites such as amino acids; for instance, droughted plants resorbed a smaller fraction of elemental N from their leaves than plants exposed to the ambient control. In contrast, plants in drought treatment resorbed amino acids more efficiently (>90%) than those in ambient (65-77%) or wet (42-58%) treatments. Across the climate treatments, the RE of elemental N correlated negatively with tissue tannin concentration, indicating that polyphenols produced in leaves under climatic stress could interfere with N resorption. Thus, senesced leaves from drier conditions might have a lower nutritive value to soil heterotrophs during the initial stages of litter decomposition despite a higher elemental N content of these tissues. Our results suggest that N

  11. Species differences in timing of leaf fall and foliage chemistry modify nutrient resorption efficiency in deciduous temperate forest stands.

    PubMed

    Niinemets, Ulo; Tamm, Ulo

    2005-08-01

    Extensive variation in fractional resorption of mineral elements from plant leaves is still not fully understood. In multi-species forest stands, species leaf fall phenology and leaf constitution may significantly modify the timing of nutrient return to the soil and overall plant nutrient loss. We studied leaf fall and nutrient loss kinetics, and leaf composition in three natural, temperate, deciduous broadleaf forest stands to determine the role of timing of leaf abscission and nutrient immobilization in cell walls on nutrient resorption efficiency of senescing leaves. Nitrogen (N), phosphorus and potassium contents decreased continuously in attached leaves after peak physiological activity during mid-season. Changes in nutrient contents of attached leaves were paralleled by decreases in nutrient contents in freshly fallen leaf litter. In different species and for different nutrients, resorption of nutrients from senescing leaves proceeded with different kinetics. The maximum nutrient resorption efficiency (the fraction of specific nutrient resorbed from the leaves at the end of leaf fall) did not depend on the mid-seasonal nutrient concentration. Species with earlier leaf fall resorbed leaf nutrients at a faster rate, partly compensating for the earlier leaf fall. Nevertheless, the litter-mass weighted mean nutrient contents in leaf litter were still larger in species with earlier leaf fall, demonstrating an inherent trade-off between early leaf fall and efficient nutrient resorption. This trade-off was most important for N. Losses of the non-mobile nutrients calcium and magnesium were unaffected by the timing of leaf fall. There was large variation in the maximum N resorption efficiency among species. Correlations among leaf chemical variables suggested that the maximum N resorption efficiency decreased with the increasing fraction of cell walls in the leaves, possibly due to a greater fraction of N occluded in cell wall matrix. We conclude that species leaf

  12. The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats.

    PubMed

    Benis, K A; Schneider, G B

    1996-10-15

    macrophage/osteoclast lineage can be functionally upregulated with the subsequent addition of DBP-MAF to perform the activities of phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did not support colony development as in CSF-1 or the combination treatment. The recruitment and activation of cells into the macrophage/ osteoclast lineage may help to correct the bone and immune defects found in diseases demonstrating a significant lack of myeloid cells, as well as neutrophilia disorders and the disease, osteopetrosis. PMID:8874186

  13. Using Micro-Computed Tomography to Evaluate the Dynamics of Orthodontically Induced Root Resorption Repair in a Rat Model

    PubMed Central

    Yang, Fengxue; Wei, Shicheng; Dai, Hongwei

    2016-01-01

    Objective To observe dynamic changes in root resorption repair, tooth movement relapse and alveolar bone microstructure following the application of orthodontic force. Materials and Methods Forces of 20 g, 50 g or 100 g were delivered to the left maxillary first molars of fifteen 10-week-old rats for 14 days. Each rat was subjected to micro-computed tomography scanning at 0, 3, 7, 10, 14, 28 and 42 days after force removal. The root resorption crater volume, tooth movement relapse and alveolar bone microarchitecture were measured at each time point. Results From day 3 to day 14, the root resorption volume decreased significantly in each group. In the 20-g force group, the root resorption volume gradually stabilized after 14 days, whereas in the 50-g and 100-g force groups, it stabilized after 28 days. In all groups, tooth movement relapsed significantly from day 0 to day 14 and then remained stable. From day 3 to day 10, the 20-g group exhibited faster relapse than the 50-g and 100-g groups. In all groups, the structure model index and trabecular separation decreased slowly from day 0 to day 10 and eventually stabilized. Trabecular number increased slowly from day 0 to day 7 and then stabilized. Conclusions The initial stage of root resorption repair did not change significantly and was followed by a dramatic repair period before stabilizing. The most serious tooth movement relapse occurred immediately after the appliance was removed, and then the tooth completely returned to the original position. PMID:26930605

  14. Disruption of the dynein-dynactin complex unveils motor-specific functions in osteoclast formation and bone resorption.

    PubMed

    Ng, Pei Ying; Cheng, Tak Sum; Zhao, Haibo; Ye, Shiqiao; Sm Ang, Estabelle; Khor, Ee Cheng; Feng, Hao-Tian; Xu, Jiake; Zheng, Ming H; Pavlos, Nathan J

    2013-01-01

    Osteoclastic bone resorption requires strict interplay between acidified carrier vesicles, motor proteins, and the underlying cytoskeleton in order to sustain the specialized structural and functional polarization of the ruffled border. Cytoplasmic dynein, a large processive mechanochemical motor comprising heavy, intermediate, and light chains coupled to the dynactin cofactor complex, powers unilateral motility of diverse cargos to microtubule minus-ends. We have recently shown that regulators of the dynein motor complex constitute critical components of the osteoclastic bone resorptive machinery. Here, by selectively modulating endogenous dynein activity, we show that the integrity of the dynein-dynactin motor complex is an essential requirement for both osteoclast formation and function. Systematic dissection of the osteoclast dynein-dynactin complex revealed that it is differentially localized throughout RANKL-induced osteoclast formation and activation, undergoing microtubule-coupled reorganization upon the establishment of cellular polarization. In osteoclasts actively resorbing bone, dynein-dynactin intimately co-localizes with the CAP-Gly domain-containing microtubule plus-end protein CLIP-170 at the resorptive front, thus orientating the ruffled border as a microtubule plus-end domain. Unexpectedly, disruption of the dynein-dynactin complex by exogenous p50/dynamitin expression retards osteoclast formation in vitro, owing largely to prolonged mitotic stasis of osteoclast progenitor cells. More importantly, loss of osteoclastic dynein activity results in a drastic redistribution of key intracellular organelles, including the Golgi and lysosomes, an effect that coincides with impaired cathepsin K secretion and diminished bone resorptive function. Collectively, these data unveil a previously unrecognized role for the dynein-dynactin motor complex in osteoclast formation and function, serving not only to regulate their timely maturation but also the delivery

  15. Purinergic signaling during macrophage differentiation results in M2 alternative activated macrophages.

    PubMed

    Barberà-Cremades, Maria; Baroja-Mazo, Alberto; Pelegrín, Pablo

    2016-02-01

    Macrophages represent a highly heterogenic cell population of the innate immune system, with important roles in the initiation and resolution of the inflammatory response. Purinergic signaling regulates both M1 and M2 macrophage function at different levels by controlling the secretion of cytokines, phagocytosis, and the production of reactive oxygen species. We found that extracellular nucleotides arrest macrophage differentiation from bone marrow precursors via adenosine and P2 receptors. This results in a mature macrophage with increased expression of M2, but not M1, genes. Similar to adenosine and ATP, macrophage growth arrested with LPS treatment resulted in an increase of the M2-related marker Ym1. Recombinant Ym1 was able to affect macrophage proliferation and could, potentially, be involved in the arrest of macrophage growth during hematopoiesis.

  16. Effect of alveolar macrophages on Toxoplasma gondii.

    PubMed Central

    Ryning, F W; Remington, J S

    1977-01-01

    As pulmonary involvement can occur in disseminated toxoplasmosis in immunosuppressed patients, studies were initiated to define local mechanisms of resistance of the lung to Toxoplasma gondii. Alveolar macrophages were obtained from normal mice and mice chronically infected with T. gondii by bronchopulmonary lavage and cultured in vitro. Although normal alveolar macrophages were difficult to infect with Toxoplasma, they supported intracellular multiplication of this organism. When exposed to Toxoplasma that had been pretreated with heat-inactivated serum containing specific antibody, the number of intracellular organisms increased remarkably, and the macrophages destroyed the coated parasites. After development of chronic infections with Toxoplasma, there was a transient period during which a striking increase in numbers of alveolar macrophages was observed in lavage specimens. These macrophages differed from those of normal alveolar macrophages. There was a greater percentage of large cells, a greater tendency to spread on glass, and an increased number of intracellular Toxoplasma, and the cells were activated to kill or inhibit multiplication of the parasite. During the period when activated macrophages were demonstrable in bronchopulmonary washings, histological changes in the lungs revealed a marked mononuclear cell infiltrate. These studies support a role for the activated alveolar macrophage as an effector in resistance of the lung to infection with Toxoplasma. PMID:591065

  17. A broken krebs cycle in macrophages.

    PubMed

    O'Neill, Luke A J

    2015-03-17

    Macrophages undergo metabolic rewiring during polarization but details of this process are unclear. In this issue of Immunity, Jha et al. (2015) report a systems approach for unbiased analysis of cellular metabolism that reveals key metabolites and metabolic pathways required for distinct macrophage polarization states.

  18. Interaction of Chlamydiae with human macrophages.

    PubMed

    Herweg, Jo-Ana; Rudel, Thomas

    2016-02-01

    The phylum Chlamydiae contains several members that are well-known human pathogens, like Chlamydia trachomatis and C. pneumoniae. Establishing a chronic bacterial infection requires the active evasion of the host immune response. A major arm of the innate immune defence is constituted by macrophages, which fight infections by removing bacteria and triggering an adaptive immune response. However, some pathogenic Chlamydia infect and survive in macrophages at least for a certain period of time. Therefore, macrophages can serve as vehicles for the dissemination of bacterial infections from the primary infection site via the urogenital or respiratory tract to distant sites in the body. The capacity to infect macrophages seems to depend on the chlamydial strain and the source of macrophages. In vitro infections of macrophages with C. trachomatis, C. psittaci and C. pneumoniae reveal low efficiency of infection and progeny formation, as well as failure to develop mature inclusions. In contrast, the emerging pathogen, Simkania negevensis, actively replicates in macrophages. Here we summarize the current knowledge of the intracellular and molecular key mechanisms of C. trachomatis, C. pneumoniae and S. negevensis infections in human macrophages. PMID:26613554

  19. Macrophage polarization in virus-host interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macrophage involvement in viral infections and antiviral states is common. However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses. Recent studies have reveal...

  20. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  1. Macrophagic myofasciitis: characterization and pathophysiology

    PubMed Central

    Gherardi, Romain K.; Authier, François-Jérôme

    2012-01-01

    Summary Aluminium oxyhydroxide (alum), a nano-crystaline compound forming agglomerates, has been introduced in vaccine for its immunologic adjuvant effect in 1927. Alum is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remains incompletely understood. Although generally well tolerated, alum may occasionally cause disabling health problems in presumably susceptible individuals. A small proportion of vaccinated people present with delayed onset of diffuse myalgia, chronic fatigue and cognitive dysfunction, and exhibit very long-term persistence of alum-loaded macrophages at site of previous intra-muscular (i.m.) immunization, forming a granulomatous lesion called macrophagic myofasciitis (MMF). Clinical symptoms associated with MMF are paradigmatic of the recently delineated “autoimmune/inflammatory syndrome induced by adjuvants” (ASIA). The stereotyped cognitive dysfunction is reminiscent of cognitive deficits described in foundry workers exposed to inhaled Al particles. Alum safety concerns will largely depend on whether the compound remains localized at site of injection or may diffuse and accumulate in distant organs. Animal experiments indicate that biopersistent nanomaterials taken-up by monocytes-lineage cells in tissues, e.g. fluorescent alum surrogates, can first translocate to draining lymph nodes, and thereafter circulate in blood within phagocytes and reach the spleen, and, eventually, slowly accumulate in brain. PMID:22235051

  2. Mycobacteria, metals, and the macrophage.

    PubMed

    Neyrolles, Olivier; Wolschendorf, Frank; Mitra, Avishek; Niederweis, Michael

    2015-03-01

    Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here, we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies.

  3. Mycobacteria, Metals, and the Macrophage

    PubMed Central

    Niederweis, Michael; Wolschendorf, Frank; Mitra, Avishek; Neyrolles, Olivier

    2015-01-01

    Summary Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies. PMID:25703564

  4. Mycobacteria, metals, and the macrophage.

    PubMed

    Neyrolles, Olivier; Wolschendorf, Frank; Mitra, Avishek; Niederweis, Michael

    2015-03-01

    Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here, we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies. PMID:25703564

  5. ROCK inhibition impedes macrophage polarity and functions.

    PubMed

    Liu, Yianzhu; Tejpal, Neelam; You, Junping; Li, Xian C; Ghobrial, Rafik M; Kloc, Malgorzata

    2016-02-01

    Macrophages play an important role in immune responses including allograft rejection and they are one of the potential targets of anti-rejection therapies in organ transplantation. Macrophage alloreactivity relies on their phenotype/polarity, motility, phagocytosis and matrix degradation, which in turn depend on proper functioning of actin cytoskeleton and its regulators, the small GTPase RhoA and its downstream effector the Rho-associated protein kinase (ROCK). Several laboratories showed that administration of ROCK inhibitor Y-27632 to the graft recipient inhibits chronic rejection or rodent cardiac allografts. Here we studied the effect of Y-27632 on mouse peritoneal macrophage structure, polarity and functions in in vitro assays. We show that Y-27632 inhibitor affects macrophage phenotype/polarity, phagocytosis, migration, and matrix degradation. These novel findings suggest that the impediment of macrophage structure and function via interference with the RhoA/ROCK pathway has a potential to be therapeutically effective in organ transplantation.

  6. [Molecular mechanisms regulating the activity of macrophages].

    PubMed

    Onoprienko, L V

    2011-01-01

    This article reviews modern concepts of the most common types of macrophage activation: classical, alternative, and type II. Molecular mechanisms of induction and regulation of these three types of activation are discussed. Any population of macrophages was shown to change its properties depending on its microenvironment and concrete biological situation (the "functional plasticity of macrophages"). Many intermediate states of macrophages were described along with the most pronounced and well-known activation types (classical activation, alternative activation, and type II activation). These intermediate states are characterized by a variety of combinations of their biological properties, including elements of the three afore mentioned types of activation. Macrophage activity is regulated by a complex network of interrelated cascade mechanisms.

  7. Extracellular calcium (Ca2+o)-sensing receptor in a mouse monocyte-macrophage cell line (J774): potential mediator of the actions of Ca2+o on the function of J774 cells

    NASA Technical Reports Server (NTRS)

    Yamaguchi, T.; Kifor, O.; Chattopadhyay, N.; Bai, M.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

    1998-01-01

    The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone remodeling and may play a role in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for bone marrow mononuclear cells in the vicinity, leading us to investigate whether such mononuclear cells express the CaR. In this study, we used the mouse J774 cell line, which exhibits a pure monocyte-macrophage phenotype. Both immunocytochemistry and Western blot analysis, using polyclonal antisera specific for the CaR, detected CaR protein in J774 cells. The use of reverse transcriptase-polymerase chain reaction with CaR-specific primers, including a set of intron-spanning primers, followed by nucleotide sequencing of the amplified products, also identified CaR transcripts in J774 cells. Exposure of J774 cells to high Ca2+o (2.8 mM or more) or the polycationic CaR agonist, neomycin (100 microM), stimulated both chemotaxis and DNA synthesis in J774 cells. Therefore, taken together, our data strongly suggest that the monocyte-macrophage cell line, J774, possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney.

  8. Preadipocyte conversion to macrophage. Evidence of plasticity.

    PubMed

    Charrière, Guillaume; Cousin, Béatrice; Arnaud, Emmanuelle; André, Mireille; Bacou, Francis; Penicaud, Luc; Casteilla, Louis

    2003-03-14

    Preadipocytes are present throughout adult life in adipose tissues and can proliferate and differentiate into mature adipocytes according to the energy balance. An increasing number of reports demonstrate that cells from adipose lineages (preadipocytes and adipocytes) and macrophages share numerous functional or antigenic properties. No large scale comparison reflecting the phenotype complexity has been performed between these different cell types until now. We used profiling analysis to define the common features shared by preadipocyte, adipocyte, and macrophage populations. Our analysis showed that the preadipocyte profile is surprisingly closer to the macrophage than to the adipocyte profile. From these data, we hypothesized that in a macrophage environment preadipocytes could effectively be converted into macrophages. We injected labeled stroma-vascular cells isolated from mouse white adipose tissue or 3T3-L1 preadipocyte cell line into the peritoneal cavity of nude mice and investigated changes in their phenotype. Preadipocytes rapidly and massively acquired high phagocytic activity and index. 60-70% of preadipocytes also expressed five macrophage-specific antigens: F4/80, Mac-1, CD80, CD86, and CD45. These values were similar to those observed for peritoneal macrophages. In vitro experiments showed that cell-to-cell contact between preadipocytes and peritoneal macrophages partially induced this preadipocyte phenotype conversion. Overall, these results suggest that preadipocyte and macrophage phenotypes are very similar and that preadipocytes have the potential to be very efficiently and rapidly converted into macrophages. This work emphasizes the great cellular plasticity of adipose precursors and reinforces the link between adipose tissue and innate immunity processes. PMID:12519759

  9. Suppressive effects of ketamine on macrophage functions

    SciTech Connect

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M. . E-mail: rmchen@tmu.edu.tw

    2005-04-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 {mu}M ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 {mu}M, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 {mu}M, did not affect the chemotactic activity of macrophages. Administration of 1000 {mu}M ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-{alpha}, IL-1{beta}, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-{alpha}, IL-1{beta}, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 {mu}M) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.

  10. The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF.

    PubMed

    Odgren, P R; Popoff, S N; Safadi, F F; MacKay, C A; Mason-Savas, A; Seifert, M F; Marks, S C

    1999-08-01

    The osteopetrotic rat mutation toothless (tl) is characterized by little or no bone resorption, few osteoclasts and macrophages, and chondrodysplasia at the growth plates. Short-term treatment of tl rats with colony-stimulating factor-1 (CSF-1) has been shown to increase the number of osteoclasts and macrophages, producing dramatic resolution of skeletal sclerosis at some, but not all, sites. Defects in production of vitamin D-binding protein-macrophage activating factor (DBP-MAF) have been identified in two other independent osteopetrotic mutations of the rat (op and ia), and two in the mouse (op and mi), in which macrophages and osteoclasts can be activated by the administration of exogenous DBP-MAF. The present studies were undertaken to examine the histology and residual growth defects in tl rats following longer CSF-1 treatments, to investigate the possibility that exogenous DBP-MAF might act synergistically with CSF-1 to improve the tl phenotype, and to assess the integrity of the endogenous DBP-MAF pathway in this mutation. CSF-1 treatment-with or without DBP-MAF-induced resorption of metaphyseal bone to the growth plate on the marrow side, improved slightly but did not normalize long bone growth, and caused no improvement in the abnormal histology of the growth plate. Injections of lysophosphatidylcholine (lyso-Pc) to prime macrophage activation via the DBP-MAF pathway raised superoxide production to similar levels in peritoneal macrophages from both normal and mutant animals, indicating no defect in the DBP-MAF pathway in tl rats. Interestingly, pretreatments with CSF-1 alone also increased superoxide production, although the mechanism for this remains unknown. In summary, we find that, unlike other osteopetrotic mutations investigated to date, the DBP-MAF pathway does not appear to be defective in the tl rat; that additional DBP-MAF does not augment the beneficial skeletal effects seen with CSF-1 alone; and that the growth plate chondrodystrophy seen in

  11. Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization.

    PubMed

    Liu, Kun; Zhao, Enpeng; Ilyas, Ghulam; Lalazar, Gadi; Lin, Yu; Haseeb, Muhammad; Tanaka, Kathryn E; Czaja, Mark J

    2015-01-01

    Recent evidence that excessive lipid accumulation can decrease cellular levels of autophagy and that autophagy regulates immune responsiveness suggested that impaired macrophage autophagy may promote the increased innate immune activation that underlies obesity. Primary bone marrow-derived macrophages (BMDM) and peritoneal macrophages from high-fat diet (HFD)-fed mice had decreased levels of autophagic flux indicating a generalized impairment of macrophage autophagy in obese mice. To assess the effects of decreased macrophage autophagy on inflammation, mice with a Lyz2-Cre-mediated knockout of Atg5 in macrophages were fed a HFD and treated with low-dose lipopolysaccharide (LPS). Knockout mice developed systemic and hepatic inflammation with HFD feeding and LPS. This effect was liver specific as knockout mice did not have increased adipose tissue inflammation. The mechanism by which the loss of autophagy promoted inflammation was through the regulation of macrophage polarization. BMDM and Kupffer cells from knockout mice exhibited abnormalities in polarization with both increased proinflammatory M1 and decreased anti-inflammatory M2 polarization as determined by measures of genes and proteins. The heightened hepatic inflammatory response in HFD-fed, LPS-treated knockout mice led to liver injury without affecting steatosis. These findings demonstrate that autophagy has a critical regulatory function in macrophage polarization that downregulates inflammation. Defects in macrophage autophagy may underlie inflammatory disease states such as the decrease in macrophage autophagy with obesity that leads to hepatic inflammation and the progression to liver injury. PMID:25650776

  12. Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization.

    PubMed

    Liu, Kun; Zhao, Enpeng; Ilyas, Ghulam; Lalazar, Gadi; Lin, Yu; Haseeb, Muhammad; Tanaka, Kathryn E; Czaja, Mark J

    2015-01-01

    Recent evidence that excessive lipid accumulation can decrease cellular levels of autophagy and that autophagy regulates immune responsiveness suggested that impaired macrophage autophagy may promote the increased innate immune activation that underlies obesity. Primary bone marrow-derived macrophages (BMDM) and peritoneal macrophages from high-fat diet (HFD)-fed mice had decreased levels of autophagic flux indicating a generalized impairment of macrophage autophagy in obese mice. To assess the effects of decreased macrophage autophagy on inflammation, mice with a Lyz2-Cre-mediated knockout of Atg5 in macrophages were fed a HFD and treated with low-dose lipopolysaccharide (LPS). Knockout mice developed systemic and hepatic inflammation with HFD feeding and LPS. This effect was liver specific as knockout mice did not have increased adipose tissue inflammation. The mechanism by which the loss of autophagy promoted inflammation was through the regulation of macrophage polarization. BMDM and Kupffer cells from knockout mice exhibited abnormalities in polarization with both increased proinflammatory M1 and decreased anti-inflammatory M2 polarization as determined by measures of genes and proteins. The heightened hepatic inflammatory response in HFD-fed, LPS-treated knockout mice led to liver injury without affecting steatosis. These findings demonstrate that autophagy has a critical regulatory function in macrophage polarization that downregulates inflammation. Defects in macrophage autophagy may underlie inflammatory disease states such as the decrease in macrophage autophagy with obesity that leads to hepatic inflammation and the progression to liver injury.

  13. Changing pattern of the subcellular distribution of erythroblast macrophage protein (Emp) during macrophage differentiation.

    PubMed

    Soni, Shivani; Bala, Shashi; Kumar, Ajay; Hanspal, Manjit

    2007-01-01

    Erythroblast macrophage protein (Emp) mediates the attachment of erythroid cells to macrophages and is required for normal differentiation of both cell lineages. In erythroid cells, Emp is believed to be involved in nuclear extrusion, however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp. Macrophages of varying maturity were examined by immunofluorescence microscopy and biochemical methods. Our data show that Emp is expressed in all stages of maturation, but its localization pattern changes dramatically during maturation: in immature macrophages, a substantial fraction of Emp is associated with the nuclear matrix, whereas in more mature cells, Emp is expressed largely at cell surface. Pulse-chase experiments show that nascent Emp migrates intracellularly from the cytoplasm to the plasma membrane more efficiently in mature macrophages than in immature cells. Incubation of erythroid cells with macrophages in culture shows that erythroid cells attach to mature macrophages but not to immature macrophage precursors. Together, our data show that the temporal and spatial expression of Emp correlates with its role in erythroblastic island formation and suggest that Emp may be involved in multiple cellular functions.

  14. Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363.

    PubMed

    Buchebner, Marlene; Pfeifer, Thomas; Rathke, Nora; Chandak, Prakash G; Lass, Achim; Schreiber, Renate; Kratzer, Adelheid; Zimmermann, Robert; Sattler, Wolfgang; Koefeler, Harald; Fröhlich, Eleonore; Kostner, Gerhard M; Birner-Gruenberger, Ruth; Chiang, Kyle P; Haemmerle, Guenter; Zechner, Rudolf; Levak-Frank, Sanja; Cravatt, Benjamin; Kratky, Dagmar

    2010-10-01

    Cholesteryl ester (CE) accumulation in macrophages represents a crucial event during foam cell formation, a hallmark of atherogenesis. Here we investigated the role of two previously described CE hydrolases, hormone-sensitive lipase (HSL) and KIAA1363, in macrophage CE hydrolysis. HSL and KIAA1363 exhibited marked differences in their abilities to hydrolyze CE, triacylglycerol (TG), diacylglycerol (DG), and 2-acetyl monoalkylglycerol ether (AcMAGE), a precursor for biosynthesis of platelet-activating factor (PAF). HSL efficiently cleaved all four substrates, whereas KIAA1363 hydrolyzed only AcMAGE. This contradicts previous studies suggesting that KIAA1363 is a neutral CE hydrolase. Macrophages of KIAA1363(-/-) and wild-type mice exhibited identical neutral CE hydrolase activity, which was almost abolished in tissues and macrophages of HSL(-/-) mice. Conversely, AcMAGE hydrolase activity was diminished in macrophages and some tissues of KIAA1363(-/-) but unchanged in HSL(-/-) mice. CE turnover was unaffected in macrophages lacking KIAA1363 and HSL, whereas cAMP-dependent cholesterol efflux was influenced by HSL but not by KIAA1363. Despite decreased CE hydrolase activities, HSL(-/-) macrophages exhibited CE accumulation similar to wild-type (WT) macrophages. We conclude that additional enzymes must exist that cooperate with HSL to regulate CE levels in macrophages. KIAA1363 affects AcMAGE hydrolase activity but is of minor importance as a direct CE hydrolase in macrophages.

  15. NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization.

    PubMed

    Liu, Qihui; Tian, Yuan; Zhao, Xiangfeng; Jing, Haifeng; Xie, Qi; Li, Peng; Li, Dong; Yan, Dongmei; Zhu, Xun

    2015-10-01

    Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-GuC)rin) activates disabled naC/ve macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-N2) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.

  16. Specific Neuropilins Expression in Alveolar Macrophages among Tissue-Specific Macrophages

    PubMed Central

    Aung, Naing Ye; Ohe, Rintaro; Meng, Hongxue; Kabasawa, Takanobu; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-01-01

    In the immune system, neuropilins (NRPs), including NRP-1 and NRP-2, are expressed in thymocytes, dendritic cells, regulatory T cells and macrophages. Their functions on immune cells around the neoplastic cells vary into pro-angiogenesis, tumor progression and anti-angiogenesis according to their ligands. Even though NRPs expression on malignant tumors and immune system has studied, a PubMed-based literature query did not yield any articles describing NRPs expression on tissue-specific macrophages. The aims of this study were (i) to detect NRPs expression on tissue-specific macrophages in the brain, liver, spleen, lymph node and lung; (ii) to observe NRPs expression in classes of macrophages, including alveolar macrophages (AMs), bronchial macrophages (BMs), interstitial macrophages (IMs), intravascular macrophages (IVMs) and macrophage subsets (M1, M2 and Mox) in lung; and (iii) to detect the co-expression of NRPs and dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in AMs. Both NRPs were specifically detected in AMs among tissue-specific macrophages by immunohistochemistry (IHC). NRPs mRNA expression levels were characterized in normal lung by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ-polymerase chain reaction (in situ-PCR). The expression of both NRPs was detected in AMs, BMs and IVMs by IHC. The frequency of NRPs+ AMs in lung tissue adjacent to the cancer margin was significantly higher than the frequencies in inflamed and normal lung tissue. Double and triple IHC demonstrated that NRPs are expressed on all macrophage subsets in lung. Double IHC showed co-expression of DC-SIGN and NRPs in AMs. This study demonstrated for the first time the specific expression of both NRPs in AMs among tissue-specific macrophages and their expression on M1, M2 and Mox macrophages. Furthermore, the possible origin of AMs from blood monocytes could be suggested from a co-expression of NRPs and DC-SIGN. PMID:26900851

  17. Volumetric Measurement of Root Resorption following Molar Mini-Screw Implant Intrusion Using Cone Beam Computed Tomography

    PubMed Central

    Li, Wen; Chen, Fei; Zhang, Feng; Ding, Wanghui; Ye, Qingsong; Shi, Jiejun; Fu, Baiping

    2013-01-01

    Objective Molar intrusion by mini-screw implantation can cause different degrees of root resorption. However, most methods (2-D and 3-D) used for evaluating root resorption have focused on the root length without considering 3-D resorption. The purpose of this study was to volumetrically evaluate root resorption using cone beam computed tomography(CBCT) after mini-screw implant intrusion. Materials and Methods 1. The volumes of 32 teeth were measured using CBCT and laser scanning to verify the accuracy of CBCT. 2. Twelve overerupted molars from adult patients were investigated in this study. After mini-screw implants were inserted into the buccal and palatal alveolar bones, 150 g of force was applied to the mini-screw implants on each side to intrude the molars. CBCT images of all patients were taken immediately prior to intrusion and after intrusion. The volumes of the roots were calculated using the Mimics software program. The differences between the pre-intrusion and post-intrusion root volumes were statistically evaluated with a paired-samples t-test. In addition, the losses of the roots were statistically compared with each other using one-way analysis of variance at the P<0.05 level. Results No statistically significant volume differences were observed between the physical (laser scanning) and CBCT measurements (P>0.05). The overerupted molars were significantly intruded (P<0.05), and the average intrusion was 3.30±1.60 mm. The differences between the pre-intrusion and post-intrusion root volumes were statistically significant for all of the roots investigated (P<0.05). The roots were sorted by volume loss in descending order as follows: mesiobuccal, palatal, and distobuccal. Statistical significance was achieved among the three roots. The average total resorption for each tooth was 58.39±1.54 mm3. Conclusion Volume measurement using CBCT was able to effectively evaluate root resorption caused by mini-screw intrusion. The highest volume loss was observed

  18. Indirect effects of invasive predators on litter decomposition and nutrient resorption on seabird-dominated islands.

    PubMed

    Wardle, David A; Bellingham, Peter J; Bonner, Karen I; Mulder, Christa P H

    2009-02-01

    Despite recent interest in the ecosystem impacts of invasive aboveground organisms, most work in this area has focused on effects of invasive plants, and the effects of invasive herbivores and predators remain poorly understood. We studied 18 forested, offshore islands in northern New Zealand. Nine of these host high densities of burrowing seabirds that serve as ecosystem drivers by transporting nutrients from the ocean to land. The other nine have been invaded over the past 50-150 years by rat species introduced from Europe which serve as predators of seabird eggs and chicks and severely reduce their densities. We collected fully expanded leaves and fresh leaf litter from invaded and uninvaded islands for each of 12 perennial plant species that represent a wide spectrum of life forms from ground dwelling to emergent canopy species. We found that, across these species, invasion by rats significantly reduced nitrogen (N) but not phosphorus (P) concentrations of foliage and litter, promoted N but not P resorption from leaves before litter fall, and reduced the release of N but not P from decomposing litter. Rat invasion also negatively affected litter decomposability but had no overall effects on litter quality variables other than N. Our results provide evidence that rat invasion causes more conservative cycling of N but not P through foliage and litter and limitation of ecological processes by N but not P. We found few instances in which the effects of rat invasion on response variables varied significantly across plant species, meaning that invasion had similar effects for species that varied greatly in growth form and foliar and litter quality. Further, correlation analyses across the 12 species showed that foliar and litter quality traits were poor predictors of how invasion effects on resorption and decomposition variables varied among species. Our results show that the effects of invasive predators on native prey can have substantial indirect effects on

  19. Skeletal lead release during bone resorption: effect of bisphosphonate treatment in a pilot study.

    PubMed Central

    Gulson, Brian; Mizon, Karen; Smith, Howard; Eisman, John; Palmer, Jacqueline; Korsch, Michael; Donnelly, John; Waite, Kay

    2002-01-01

    There has been renewed interest in impacts on physiologic systems in the middle and older age groups, especially from fractures and hypertension. Increased blood lead (BPb) levels in postmenopausal females, which are thought to arise from bone demineralization, may also relate to other health effects including hypertension. Taking advantage of natural differences in lead isotope signature between Australian sources of lead and those from other countries, a 2-year pilot study was performed in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim of the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodeling processes. Premenopausal subjects were a woman (and male partner) from Bosnia and two women from Colombia. The postmenopausal subject was a woman from Russia. Her male partner and one man from Sri Lanka were included. Multigenerational Australian subjects were 2 perimenopausal women and 1 postmenopausal woman. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for 7-9 months before, for 3 months during, and for up to 6 months after treatment with alendronate to inhibit bone resorption. Each subject thus acted as his or her own control. As predicted, there were significant decreases in the lead isotope ratio, (206)Pb/(204)Pb, for the migrant subjects during treatment compared with the pretreatment period (p < 0.01). After cessation of treatment, an increasing isotope ratio for the postmenopausal subject (and older male partner) occurred later than for premenopausal subjects, indicative of prolonged efficacy of the alendronate for the older subjects. The average BPb concentrations in migrant subjects decreased by about 20% during the treatment compared with the pretreatment period (p < 0.01). To our knowledge, these are the first BPb concentrations reported

  20. Macrophage Migration Inhibitory Factor (MIF) Supports Homing of Osteoclast Precursors to Peripheral Osteolytic Lesions.

    PubMed

    Movila, Alexandru; Ishii, Takenobu; Albassam, Abdullah; Wisitrasameewong, Wichaya; Howait, Mohammed; Yamaguchi, Tsuguno; Ruiz-Torruella, Montserrat; Bahammam, Laila; Nishimura, Kazuaki; Van Dyke, Thomas; Kawai, Toshihisa

    2016-09-01

    By binding to its chemokine receptor CXCR4 on osteoclast precursor cells (OCPs), it is well known that stromal cell-derived factor-1 (SDF-1) promotes the chemotactic recruitment of circulating OCPs to the homeostatic bone remodeling site. However, the engagement of circulating OCPs in pathogenic bone resorption remains to be elucidated. The present study investigated a possible chemoattractant role of macrophage migration inhibitory factor (MIF), another ligand for C-X-C chemokine receptor type 4 (CXCR4), in the recruitment of circulating OCPs to the bone lytic lesion. To accomplish this, we used Csf1r-eGFP-knock-in (KI) mice to establish an animal model of polymethylmethacrylate (PMMA) particle-induced calvarial osteolysis. In the circulating Csf1r-eGFP+ cells of healthy Csf1r-eGFP-KI mice, Csf1r+/CD11b+ cells showed a greater degree of RANKL-induced osteoclastogenesis compared to a subset of Csf1r+/RANK+ cells in vitro. Therefore, Csf1r-eGFP+/CD11b+ cells were targeted as functionally relevant OCPs in the present study. Although expression of the two cognate receptors for MIF, CXCR2 and CXCR4, was elevated on Csf1r+/CD11b+ cells, transmigration of OCPs toward recombinant MIF in vitro was facilitated by ligation with CXCR4, but not CXCR2. Meanwhile, the level of PMMA-induced bone resorption in calvaria was markedly greater in wild-type (WT) mice compared to that detected in MIF-knockout (KO) mice. Interestingly, in contrast to the elevated MIF, diminished SDF-1 was detected in a particle-induced bone lytic lesion of WT mice in conjunction with an increased number of infiltrating CXCR4+ OCPs. However, such diminished SDF-1 was not found in the PMMA-injected calvaria of MIF-KO mice. Furthermore, stimulation of osteoblasts with MIF in vitro suppressed their production of SDF-1, suggesting that MIF can downmodulate SDF-1 production in bone tissue. Systemically administered anti-MIF neutralizing monoclonal antibody (mAb) inhibited the homing of CXCR4+ OCPs, as well as

  1. Nobiletin, a polymethoxy flavonoid, suppresses bone resorption by inhibiting NFκB-dependent prostaglandin E synthesis in osteoblasts and prevents bone loss due to estrogen deficiency.

    PubMed

    Harada, Suguru; Tominari, Tsukasa; Matsumoto, Chiho; Hirata, Michiko; Takita, Morichika; Inada, Masaki; Miyaura, Chisato

    2011-01-01

    Nobiletin, a polymethoxy flavonoid, prevents cancer and inflammation, but the roles of nobiletin in bone are unclear. We examined the effects of nobiletin on bone resorption in vitro and on bone mass in ovariectomized (OVX) mice in vivo. In vitro, nobiletin suppressed osteoclast formation and bone resorption induced by interleukin (IL)-1. Nobiletin suppressed the expression of cyclooxygenase-2, NFκB-dependent transcription, and prostaglandin E (PGE) production induced by IL-1 in osteoblasts. OVX mice showed severe bone loss in the femur by increased bone resorption due to estrogen deficiency, and nobiletin significantly restored the bone mass. Nobiletin could be beneficial to bone health in postmenopausal women.

  2. Ontogeny of Tissue-Resident Macrophages

    PubMed Central

    Hoeffel, Guillaume; Ginhoux, Florent

    2015-01-01

    The origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. Originally described as part of the mononuclear phagocyte system, macrophages were long thought to derive solely from adult blood circulating monocytes. However, accumulating evidence now shows that certain macrophage populations are in fact independent from monocyte and even from adult bone marrow hematopoiesis. These tissue-resident macrophages derive from sequential seeding of tissues by two precursors during embryonic development. Primitive macrophages generated in the yolk sac (YS) from early erythro-myeloid progenitors (EMPs), independently of the transcription factor c-Myb and bypassing monocytic intermediates, first give rise to microglia. Later, fetal monocytes, generated from c-Myb+ EMPs that initially seed the fetal liver (FL), then give rise to the majority of other adult macrophages. Thus, hematopoietic stem cell-independent embryonic precursors transiently present in the YS and the FL give rise to long-lasting self-renewing macrophage populations. PMID:26441990

  3. Macrophages in diabetic gastroparesis– the missing link?

    PubMed Central

    Neshatian, Leila; Gibbons, Simon J.; Farrugia, Gianrico

    2015-01-01

    Background Diabetic gastroparesis results in significant morbidity for patients and major economic burden for society. Treatment options for diabetic gastroparesis are currently directed at symptom control rather than the underlying disease and are limited. The pathophysiology of diabetic gastroparesis includes damage to intrinsic and extrinsic neurons, smooth muscle and interstitial cells of Cajal (ICC). Oxidative damage in diabetes appears to be one of the primary insults involved in the pathogenesis of several complications of diabetes, including gastroparesis. Recent studies have highlighted the potential role of macrophages as key cellular elements in the pathogenesis of diabetic gastroparesis. Macrophages are important for both homeostasis and defense against a variety of pathogens. Heme oxygenase 1 (HO1), an enzyme expressed in a subset of macrophages has emerged as a major protective mechanism against oxidative stress. Activation of macrophages with high levels of HO1 expression protects against development of delayed gastric emptying in animal models of diabetes, while activation of macrophages that do not express HO1 are linked to neuromuscular cell injury. Targeting macrophages and HO1 may therefore be a therapeutic option in diabetic gastroparesis. Purpose This report briefly reviews the pathophysiology of diabetic gastroparesis with a focus on oxidative damage and how activation and polarization of different subtypes of macrophages in the muscularis propria determines development of delay in gastric emptying or protects against its development. PMID:25168158

  4. Developmental origin of lung macrophage diversity

    PubMed Central

    Tan, Serena Y. S.; Krasnow, Mark A.

    2016-01-01

    Macrophages are specialized phagocytic cells, present in all tissues, which engulf and digest pathogens, infected and dying cells, and debris, and can recruit and regulate other immune cells and the inflammatory response and aid in tissue repair. Macrophage subpopulations play distinct roles in these processes and in disease, and are typically recognized by differences in marker expression, immune function, or tissue of residency. Although macrophage subpopulations in the brain have been found to have distinct developmental origins, the extent to which development contributes to macrophage diversity between tissues and within tissues is not well understood. Here, we investigate the development and maintenance of mouse lung macrophages by marker expression patterns, genetic lineage tracing and parabiosis. We show that macrophages populate the lung in three developmental waves, each giving rise to a distinct lineage. These lineages express different markers, reside in different locations, renew in different ways, and show little or no interconversion. Thus, development contributes significantly to lung macrophage diversity and targets each lineage to a different anatomical domain. PMID:26952982

  5. Monocytes/Macrophages Upregulate the Hyaluronidase HYAL1 and Adapt Its Subcellular Trafficking to Promote Extracellular Residency upon Differentiation into Osteoclasts

    PubMed Central

    Puissant, Emeline; Boonen, Marielle

    2016-01-01

    Osteoclasts are giant bone-resorbing cells originating from monocytes/macrophages. During their differentiation, they overexpress two lysosomal enzymes, cathepsin K and TRAP, which are secreted into the resorption lacuna, an acidified sealed area in contact with bone matrix where bone degradation takes place. Here we report that the acid hydrolase HYAL1, a hyaluronidase able to degrade the glycosaminoglycans hyaluronic acid (HA) and chondroitin sulfate, is also upregulated upon osteoclastogenesis. The mRNA expression and protein level of HYAL1 are markedly increased in osteoclasts differentiated from RAW264.7 mouse macrophages or primary mouse bone marrow monocytes compared to these precursor cells. As a result, the HYAL1-mediated HA hydrolysis ability of osteoclasts is strongly enhanced. Using subcellular fractionation, we demonstrate that HYAL1 proteins are sorted to the osteoclast lysosomes even though, in contrast to cathepsin K and TRAP, HYAL1 is poorly mannose 6-phosphorylated. We reported previously that macrophages secrete HYAL1 proforms by constitutive secretion, and that these are recaptured by the cell surface mannose receptor, processed in endosomes and sorted to lysosomes. Present work highlights that osteoclasts secrete HYAL1 in two ways, through lysosomal exocytosis and constitutive secretion, and that these cells promote the extracellular residency of HYAL1 through downregulation of the mannose receptor. Interestingly, the expression of the other main hyaluronidase, HYAL2, and of lysosomal exoglycosidases involved in HA degradation, does not increase similarly to HYAL1 upon osteoclastogenesis. Taken together, these findings point out the predominant involvement of HYAL1 in bone HA metabolism and perhaps bone remodeling via the resorption lacuna. PMID:27755597

  6. The killing of macrophages by Corynebacterium ulcerans.

    PubMed

    Hacker, Elena; Ott, Lisa; Schulze-Luehrmann, Jan; Lührmann, Anja; Wiesmann, Veit; Wittenberg, Thomas; Burkovski, Andreas

    2016-01-01

    Corynebacterium ulcerans is an emerging pathogen transmitted by a zoonotic pathway with a very broad host spectrum to humans. Despite rising numbers of infections and potentially fatal outcomes, data on the molecular basis of pathogenicity are scarce. In this study, the interaction of 2 C. ulcerans isolates - one from an asymptomatic dog, one from a fatal case of human infection - with human macrophages was investigated. C. ulcerans strains were able to survive in macrophages for at least 20 hours. Uptake led to delay of phagolysosome maturation and detrimental effects on the macrophages as deduced from cytotoxicity measurements and FACS analyses. The data presented here indicate a high infectious potential of this emerging pathogen.

  7. ERK Signaling Is Essential for Macrophage Development

    PubMed Central

    Richardson, Edward T.; Shukla, Supriya; Nagy, Nancy; Boom, W. Henry; Beck, Rose C.; Zhou, Lan; Landreth, Gary E.; Harding, Clifford V.

    2015-01-01

    Macrophages depend on colony stimulating factor 1 (also known as M-CSF) for their growth and differentiation, but the requirements for intracellular signals that lead to macrophage differentiation and function remain unclear. M-CSF is known to activate ERK1 and ERK2, but the importance of this signaling pathway in macrophage development is unknown. In these studies, we characterized a novel model of Erk1-/- Erk2flox/flox Lyz2Cre/Cre mice in which the ERK2 isoform is deleted from macrophages in the background of global ERK1 deficiency. Cultures of M-CSF-stimulated bone marrow precursors from these mice yielded reduced numbers of macrophages. Whereas macrophages developing from M-CSF-stimulated bone marrow of Erk2flox/flox Lyz2Cre/Cre mice showed essentially complete loss of ERK2 expression, the reduced number of macrophages that develop from Erk1-/- Erk2flox/flox Lyz2Cre/Cre bone marrow show retention of ERK2 expression, indicating selective outgrowth of a small proportion of precursors in which Cre-mediated deletion failed to occur. The bone marrow of Erk1-/- Erk2flox/flox Lyz2Cre/Cre mice was enriched for CD11b+ myeloid cells, CD11bhi Gr-1hi neutrophils, Lin- c-Kit+ Sca–1+ hematopoietic stem cells, and Lin- c-Kit+ CD34+ CD16/32+ granulocyte-macrophage progenitors. Culture of bone marrow Lin- cells under myeloid-stimulating conditions yielded reduced numbers of monocytes. Collectively, these data indicate that the defect in production of macrophages is not due to a reduced number of progenitors, but rather due to reduced ability of progenitors to proliferate and produce macrophages in response to M-CSF-triggered ERK signaling. Macrophages from Erk1-/- Erk2flox/flox Lyz2Cre/Cre bone marrow showed reduced induction of M-CSF-regulated genes that depend on the ERK pathway for their expression. These data demonstrate that ERK1/ERK2 play a critical role in driving M-CSF-dependent proliferation of bone marrow progenitors for production of macrophages. PMID:26445168

  8. Macrophage cell death upon intracellular bacterial infection

    PubMed Central

    Lai, Xin-He; Xu, Yunsheng; Chen, Xiao-Ming; Ren, Yi

    2015-01-01

    Macrophage-pathogen interaction is a complex process and the outcome of this tag-of-war for both sides is to live or die. Without attempting to be comprehensive, this review will discuss the complexity and significance of the interaction outcomes between macrophages and some facultative intracellular bacterial pathogens as exemplified by Francisella, Salmonella, Shigella and Yersinia. Upon bacterial infection, macrophages can die by a variety of ways, such as apoptosis, autophagic cell death, necrosis, necroptosis, oncosis, pyronecrosis, pyroptosis etc, which is the focus of this review. PMID:26690967

  9. Macrophages and Uveitis in Experimental Animal Models

    PubMed Central

    Mérida, Salvador; Palacios, Elena; Bosch-Morell, Francisco

    2015-01-01

    Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution. PMID:26078494

  10. ERK Signaling Is Essential for Macrophage Development.

    PubMed

    Richardson, Edward T; Shukla, Supriya; Nagy, Nancy; Boom, W Henry; Beck, Rose C; Zhou, Lan; Landreth, Gary E; Harding, Clifford V

    2015-01-01

    Macrophages depend on colony stimulating factor 1 (also known as M-CSF) for their growth and differentiation, but the requirements for intracellular signals that lead to macrophage differentiation and function remain unclear. M-CSF is known to activate ERK1 and ERK2, but the importance of this signaling pathway in macrophage development is unknown. In these studies, we characterized a novel model of Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) mice in which the ERK2 isoform is deleted from macrophages in the background of global ERK1 deficiency. Cultures of M-CSF-stimulated bone marrow precursors from these mice yielded reduced numbers of macrophages. Whereas macrophages developing from M-CSF-stimulated bone marrow of Erk2(flox/flox) Lyz2(Cre/Cre) mice showed essentially complete loss of ERK2 expression, the reduced number of macrophages that develop from Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) bone marrow show retention of ERK2 expression, indicating selective outgrowth of a small proportion of precursors in which Cre-mediated deletion failed to occur. The bone marrow of Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) mice was enriched for CD11b+ myeloid cells, CD11b(hi) Gr-1(hi) neutrophils, Lin- c-Kit+ Sca-1+ hematopoietic stem cells, and Lin- c-Kit+ CD34+ CD16/32+ granulocyte-macrophage progenitors. Culture of bone marrow Lin- cells under myeloid-stimulating conditions yielded reduced numbers of monocytes. Collectively, these data indicate that the defect in production of macrophages is not due to a reduced number of progenitors, but rather due to reduced ability of progenitors to proliferate and produce macrophages in response to M-CSF-triggered ERK signaling. Macrophages from Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) bone marrow showed reduced induction of M-CSF-regulated genes that depend on the ERK pathway for their expression. These data demonstrate that ERK1/ERK2 play a critical role in driving M-CSF-dependent proliferation of bone marrow progenitors for production of

  11. Extraoral Retrograde Root Canal Filling of an Orthodontic-induced External Root Resorption Using CEM Cement

    PubMed Central

    Kheirieh, Sanam; Fazlyab, Mahta; Torabzadeh, Hassan; Eghbal, Mohamad Jafar

    2014-01-01

    Inflammatory external root resorption (IERR) after orthodontic treatments is an unusual complication. This case report describes a non-vital maxillary premolar with symptomatic extensive IERR (with a crown/root ratio of 1:1) after receiving orthodontic treatment. The first appointment included drainage, chemo-mechanical preparation of the canal and intra-canal medication with calcium hydroxide (CH) along with prescription of analgesic/antibiotic. The subsequent one-week follow-up revealed the persistence of symptoms and formation of a sinus tract. Finally, extraoral endodontic treatment was planned; the tooth was atraumatically extracted and retrograde root canal filling with calcium enriched mixture (CEM) cement was placed followed by tooth replantation. Clinical signs/symptoms subsided during 7 days postoperatively. The sinus tract also resolved after one week. Six-month and one-year follow-ups revealed complete healing and a fully functional asymptomatic tooth. This case study showed favorable outcomes in a refractory periapical lesion associated with orthodontically induced extensive IERR. The chemical as well as biological properties of CEM cement may be a suitable endodontic biomaterial for these cases. PMID:24688586

  12. Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption.

    PubMed

    Chabbi-Achengli, Yasmine; Coman, Tereza; Collet, Corinne; Callebert, Jacques; Corcelli, Michelangelo; Lin, Hilène; Rignault, Rachel; Dy, Michel; de Vernejoul, Marie-Christine; Côté, Francine

    2016-04-01

    Rheumatoid arthritis is a chronic disease that results in a disabling and painful condition as it progresses to destruction of the articular cartilage and ankylosis of the joints. Although the cause of the disease is still unknown, evidence argues that autoimmunity plays an important part. There are increasing but contradictory views regarding serotonin being associated with activation of immunoinflammatory pathways and the onset of autoimmune reactions. We studied serotonin's involvement during collagen-induced arthritis in wild-type and Tph1(-/-) mice, which have markedly reduced peripheral serotonin levels. In wild-type mice, induction of arthritis triggered a robust increase in serotonin content in the paws combined with less inflammation. In Tph1(-/-) mice with arthritis, a marked increase in the clinical and pathologic arthritis scores was noticed. Specifically, in Tph1(-/-) mice with arthritis, a significant increase in osteoclast differentiation and bone resorption was observed with an increase in IL-17 levels in the paws and in Th17 lymphocytes in the draining lymph nodes, whereas T-regulatory cells were dampened. Ex vivo serotonin and agonists of the 5-HT2A and 5-HT2B receptors restored IL-17 secretion from splenocytes and Th17 cell differentiation in Tph1(-/-) mice. These findings indicate that serotonin plays a fundamental role in arthritis through the regulation of the Th17/T-regulatory cell balance and osteoclastogenesis.

  13. A rare case of impacted supernumerary premolar causing resorption of mandibular first molar

    PubMed Central

    Murali, R. V.; Gnanashanmugam, K.; Rajasekar, L.; Kularashmi, B. S.; Saravanan, B.

    2015-01-01

    The management of patients with pain in today's general practice has become a major concern and sometimes this pain is related to some rare causes. A male patient aged 26 years reported with pain in the lower left molar region (36) and then an intra-oral periapical radiograph (IOPA), and orthopantomograph was taken. IOPA revealed the presence of supernumerary premolar causing pressure and root resorption of 36. Also, there was missing 21 and proximal decay in 11. Eleven was treated endodontically, and then bridge was done in relation to 11, 21 and 22. Lower anterior crowding was also present. The treatment plan was to extract 36 followed by orthodontic extrusion of the supernumerary premolar and also the correction of lower anterior crowding. Hidden approach (lingual orthodontics) was used as the patient was insisting upon the braces not being seen outside during the course of the treatment. Later all ceramic bridge was done in relation to 11, 21 and 22. Orthodontic tooth extrusion techniques offer excellent treatment options for Partially Impacted tooth. It is a well-documented clinical method for extruding sound tooth material from within the alveolar socket by light forces. The use of lingual technique for forced eruption enhance acceptance of orthodontic treatment by adults. The treatment of a young adult patient illustrates the importance of treatment planning from one discipline to another, communication among team members and the benefits of working together in an interdisciplinary approach PMID:26015740

  14. Anti-resorptive effect of pilose antler blood (Cervus nippon Temminck) in ovariectomized rats.

    PubMed

    Yang, Jian-Hong; Cao, Yi; Wang, Rui-Lin; Fei, Yu-Rong; Zhang, Hui; Feng, Pu; Liu, Jing

    2010-06-01

    Anti-bone resorption activity of pilose antler blood (Cervus nippon Temminck) were evaluated in ovariectomized Wistar rats. The rats were randomly divided into sham operated group (SHAM), ovariectomized group (OVX) and pilose antler blood treated group. The ovariectomized rats were treated with pilose antler blood orally in 4000 microl/kg daily doses for 10 weeks. Compared with SHAM group, serum 17 beta-estradiol level decreased significantly and osteocalcin level increased significantly in OVX group, indicating successful model of osteoporosis. The experiments showed that the bone mineral density of the lumbar spine and left femur in OVX group decreased remarkably compared to SHAM group but normalized by treatment with pilose antler blood. Additionally, serum levels of insulin-like growth factor-land testosterone were lower obviously in OVX group than those in SHAM group but preserved by pilose antler blood treatment. However, no obvious changes in serum levels of calcium, phosphorus, total alkaline phosphatase and osteoprotegerin were observed among three groups. These results suggested that administration of pilose antler blood was effective in alleviating osteoporosis in ovariectomized rats.

  15. Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats.

    PubMed

    Zafar, Tasleem A; Weaver, Connie M; Zhao, Yongdong; Martin, Berdine R; Wastney, Meryl E

    2004-02-01

    Nondigestible oligosaccharides (NDO) including inulin and fructooligosaccharides (FOS) have been reported to stimulate calcium absorption. Here we report the effect of a mixture of inulin and FOS (Raftilose Synergy 1, Orafti) on calcium and bone metabolism in ovariectomized (OVX) rats. OVX rats (6 mo old) were fed a semipurified diet for 3 mo in our animal care laboratory for stabilization after ovariectomy. They were then divided into two groups (n = 13/group) and fed either a control or a NDO-supplemented diet (55 g/kg) for 21 d. Catheters were placed in their jugular veins. After 2 d, a tracer ((45)Ca) was administered by gavage or i.v. and blood was sampled for up to 300 min. Urine and fecal samples were collected for 4 d after (45)Ca administration. Femurs were measured for bone mineral density (BMD), breaking strength, and total calcium. Calcium absorption, femoral calcium content, BMD, and bone balance (V(bal)) were significantly increased (P < 0.05) by NDO, whereas the bone resorption rate relative to the bone formation rate was significantly depressed by NDO. We conclude that feeding NDO at 5.5 g/100 g for 21 d has a positive effect on calcium absorption and retention in ovariectomized rats.

  16. High Protein Intake Improves Insulin Sensitivity but Exacerbates Bone Resorption in Immobility (WISE Study)

    NASA Technical Reports Server (NTRS)

    Heer, Martina; Smith, Scott M.; Frings-Meuthen, Petra; Zwart, Sara R.; Baecker, Natalie

    2012-01-01

    Inactivity, like bed rest (BR), causes insulin resistance (IR) and bone loss even in healthy subjects. High protein intake seems to mitigate this IR but might exacerbate bone loss. We hypothesized that high protein intake (animal:vegetable protein ratio: 60:40), isocaloric, compared to the control group plus high potassium intake would prevent IR without affecting bone turnover. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 deg head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) received 1g/kg body mass/d dietary protein. Nutrition subjects (NUT, n=8) received 1.45g/kg body mass/d dietary protein plus 7.2g branched chain amino acids per day during BR. All subjects received 1670 kcal/d. Bed rest decreased glucose disposal by 35% (p<0.05) in CON. Isocaloric high protein intake prevented insulin resistance, but exacerbated bed rest induced increase in bone resorption markers C-telopeptide (> 30%) and Ntelopeptide (>20%) (both: p<0.001). Bone formation markers were unaffected by high protein intake. We conclude from these results that high protein intake might positively affect glucose tolerance, but might also foster bone loss. Further long-duration studies are mandatory before high protein intake for diabetic patients, who have an increased fracture risk, might be recommended.

  17. Knockdown of hypothalamic RFRP3 prevents chronic stress-induced infertility and embryo resorption

    PubMed Central

    Geraghty, Anna C; Muroy, Sandra E; Zhao, Sheng; Bentley, George E; Kriegsfeld, Lance J; Kaufer, Daniela

    2015-01-01

    Whereas it is well established that chronic stress induces female reproductive dysfunction, whether stress negatively impacts fertility and fecundity when applied prior to mating and pregnancy has not been explored. In this study, we show that stress that concludes 4 days prior to mating results in persistent and marked reproductive dysfunction, with fewer successful copulation events, fewer pregnancies in those that successfully mated, and increased embryo resorption. Chronic stress exposure led to elevated expression of the hypothalamic inhibitory peptide, RFamide-related peptide-3 (RFRP3), in regularly cycling females. Remarkably, genetic silencing of RFRP3 during stress using an inducible-targeted shRNA completely alleviates stress-induced infertility in female rats, resulting in mating and pregnancy success rates indistinguishable from non-stress controls. We show that chronic stress has long-term effects on pregnancy success, even post-stressor, that are mediated by RFRP3. This points to RFRP3 as a potential clinically relevant single target for stress-induced infertility. DOI: http://dx.doi.org/10.7554/eLife.04316.001 PMID:25581095

  18. Computational biomechanics of bone's responses to dental prostheses - osseointegration, remodeling and resorption

    NASA Astrophysics Data System (ADS)

    Li, Wei; Rungsiyakull, Chaiy; Field, Clarice; Lin, Daniel; Zhang, Leo; Li, Qing; Swain, Michael

    2010-06-01

    Clinical and experimental studies showed that human bone has the ability to remodel itself to better adapt to its biomechanical environment by changing both its material properties and geometry. As a consequence of the rapid development and extensive applications of major dental restorations such as implantation and fixed partial denture (FPD), the effect of bone remodeling on the success of a dental restorative surgery is becoming critical for prosthetic design and pre-surgical assessment. This paper aims to provide a computational biomechanics framework to address dental bone's responses as a result of dental restoration. It explored three important issues of resorption, apposition and osseointegration in terms of remodeling simulation. The published remodeling data in long bones were regulated to drive the computational remodeling prediction for the dental bones by correlating the results to clinical data. It is anticipated that the study will provide a more predictive model of dental bone response and help develop a new design methodology for patient-specific dental prosthetic restoration.

  19. Diamond resorption features as a new method for examining conditions of kimberlite emplacement

    NASA Astrophysics Data System (ADS)

    Fedortchouk, Yana

    2015-10-01

    The study develops a new approach utilizing parameters of trigonal etch pits on diamond crystals to infer the conditions of diamond residence in kimberlite magma. Diamond crystals from dissolution experiments conducted at 1 GPa and 1150-1350 °C in the presence of H2O-rich or CO2-rich fluid were studied with atomic force microscopy (AFM). The AFM data of resorbed diamond surfaces show that much deeper surface relief was produced in CO2 fluid. It also clearly distinguishes the profiles of the trigonal etch pits forming regular flat-bottomed trigons in H2O fluid, and round- or pointed-bottomed trigons in CO2 fluid. The relationship between the diameter and the depth of the trigonal pits is found to be another important indicator of the fluid composition. Dissolution in H2O fluid develops trigons with constant diameter and variable depth where the diameter increases with temperature. Trigons developed in CO2 fluid have a large range of diameters showing a strong positive correlation with the depth. The developed criteria applied to the natural diamond crystals from three Ekati Mine kimberlites indicate significant variation in CO2-H2O ratio and temperature of their magmatic fluid. This conclusion based on diamond resorption agrees with the mineralogy of microphenocrysts and groundmass of the studied kimberlites offering new method to study crystallization conditions of kimberlite magma.

  20. [Length and surface density of the resorption villi's blood vessels in smokers placentas].

    PubMed

    Zigić, Zlata; Bogdanović, Gordana; Ramić, Suada

    2008-01-01

    This study was conducted with intention to reveal the quantitative values of feto-maternal nutrition exchange in smokers placentas, considering the great importance of harmful influence of smoking in pregnancy. The study was done on 90 human placentas. We have divided them into three groups: 30 placentas of moderate smokers, 30 placentas of heavy smokers and control group (non-smokers). Stereologic analysis was done with multipurpose test system M42. Pregnant smokers (both moderate and heavy) had significantly lower length density of the blood vessels compared to the control group. Significantly higher surface density of the blood vessels was found in the pregnant heavy smokers. The least absolute length density of the resorption villi's blood vessels was in the pregnant heavy smokers and it was significantly lower compared to pregnant moderate smokers and control group. In the group of the pregnant heavy smokers there was statistically higher average absolute surface of the blood vessels. The intensity of smoking effects the structural changes of the placenta. Intensity of smoking during pregnancy had a great impact on the proportion of the morphologic changes of the placentas. It leads to hypoxia, which in turn may be the cause of fetal growth and developmental retardation.

  1. Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption

    PubMed Central

    Xiong, Lei; Jung, Ji-Ung; Wu, Haitao; Xia, Wen-Fang; Pan, Jin-Xiu; Shen, Chengyong; Mei, Lin; Xiong, Wen-Cheng

    2015-01-01

    Bone mass is maintained by balanced activity of osteoblasts and osteoclasts. Lrp4 (low-density lipoprotein receptor related protein 4) is a member of the LDL receptor family, whose mutations have been identified in patients with high–bone-mass disorders, such as sclerosteosis and van Buchem diseases. However, it remains unknown whether and how Lrp4 regulates bone-mass homeostasis in vivo. Here we provide evidence that Lrp4-null mutation or specific mutation in osteoblast-lineage cells increased cortical and trabecular bone mass, which was associated with elevated bone formation and impaired bone resorption. This phenotype was not observed in osteoclast-selective Lrp4 knockout mice. Mechanistic studies indicate that loss of Lrp4 function in osteoblast-lineage cells increased serum levels of sclerostin, a key factor for bone-mass homeostasis that interacts with Lrp4, but abolished the inhibition of Wnt/β-catenin signaling and osteoblastic differentiation by sclerostin. Concomitantly, sclerostin induction of RANKL (receptor activator of nuclear kappa B ligand) was impaired, leading to a lower ratio of RANKL over OPG (osteoprotegerin) (a key factor for osteoclastogenesis). Taken together, these results support the view for Lrp4 as a receptor of sclerostin to inhibit Wnt/β-catenin signaling and bone formation and identify Lrp4 as a critical player in bone-mass homeostasis. PMID:25733894

  2. Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma.

    PubMed

    Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W; Novane, Nora; Shah, Jatin J; Davis, Richard E; Hou, Jian; Gagel, Robert F; Yang, Jing

    2016-08-24

    Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. PMID:27559096

  3. Resorption of elastic fibers in monkey gingival connective tissue: ultrastructural and immunocytochemical evidence.

    PubMed

    Sawada, Takashi

    2011-04-01

    Little is known about the remodeling of elastic fibers in gingival connective tissue. In this study, elastic fibers in the lamina propria of monkey gingiva were examined by transmission electron microscopy and immunocytochemistry. Some elastic fibers were localized at invagination on the surface of the narrow processes of fibroblasts distributed among dense assemblies of collagen fibrils, and also within coated pits, which were pinching off as coated vesicles. At a higher magnification, the coated vesicles contained filamentous structures, as well as pentagonal structures similar those previously reported in elastic fibers. Immunoelectron microscopy demonstrated positive staining for fibrillin, one of the main components of microfibril, localized either in the coated pits or vesicles. These observations indicate that at least some elastic fibers were resorbed by fibroblasts, and that, in spite of the general belief that little remodeling of elastic fibers occurs under normal conditions, resorption of elastic fibers does occur in monkey gingival connective tissue. The functional significance of this is not yet clear, but it may be involved in facilitating the delicate and efficient adaptation of tissue to physical requirements during mastication.

  4. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis.

    PubMed

    Ritchlin, Christopher T; Haas-Smith, Sally A; Li, Ping; Hicks, David G; Schwarz, Edward M

    2003-03-01

    Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by extensive bone resorption. The mechanisms underlying this matrix loss have not been elucidated. We report here that blood samples from PsA patients, particularly those with bone erosions visible on plain radiographs, exhibit a marked increase in osteoclast precursors (OCPs) compared with those from healthy controls. Moreover, PsA PBMCs readily formed osteoclasts in vitro without exogenous receptor activator of NF-kappaB ligand (RANKL) or MCSF. Both osteoprotegerin (OPG) and anti-TNF antibodies inhibited osteoclast formation. Additionally, cultured PsA PBMCs spontaneously secreted higher levels of TNF-alpha than did healthy controls. In vivo, OCP frequency declined substantially in PsA patients following treatment with anti-TNF agents. Immunohistochemical analysis of subchondral bone and synovium revealed RANK-positive perivascular mononuclear cells and osteoclasts in PsA specimens. RANKL expression was dramatically upregulated in the synovial lining layer, while OPG immunostaining was restricted to the endothelium. These results suggest a model for understanding the pathogenesis of aggressive bone erosions in PsA. OCPs arise from TNF-alpha-activated PBMCs that migrate to the inflamed synovium and subchondral bone, where they are exposed to unopposed RANKL and TNF-alpha. This leads to osteoclastogenesis at the erosion front and in subchondral bone, resulting in a bidirectional assault on psoriatic bone.

  5. Prevention of bone resorption by intake of phytoestrogens in postmenopausal women: a meta-analysis.

    PubMed

    Salari Sharif, Pooneh; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2011-09-01

    Phytoestrogens as selective estrogen receptor modulators like compounds may consider as a therapeutic option in osteoporosis. In this regard, the effect of phytoestrogens on bone biomarkers was examined in several trials which their results are controversial. We aimed this meta-analysis to evaluate the net effect of phytoestrogens on bone markers. A thorough search was conducted from 2000 to 2010 in English articles. All randomized clinical trials were reviewed, and finally, 11 eligible randomized clinical trials were selected for meta-analysis. Totally 1,252 postmenopausal women were enrolled in the study by considering the changes of pyridinoline (Pyd), desoxypyridinoline (Dpyd), bone alkaline phosphatase, and osteocalcin concentrations in urine and serum after phytoestrogens consumption. The urine Pyd and Dpyd levels decreased significantly in phytoestrogens consumers. Effect size and effect size for weighted mean difference of urine Pyd levels showed -1.229171 (95% confidence interval (CI) = -1.927639 to -0.530703) and -9.780623 (95% CI = -14.240401 to -5.320845), respectively, a significant results in comparison to control group and significant results for Dpyd -0.520132 (95% CI = -0.871988 to -0.168275) and -0.818582 (95% CI = -1.247758 to -0.389407), respectively. Meta-analysis indicates that phytoestrogens intake can prevent bone resorption, but its benefits on bone formation are not significant. This favorable effect was observed in low doses and in at least 3 weeks of phytoestrogens intake.

  6. Congenital adrenal hyperplasia: a case report with premature teeth exfoliation and bone resorption.

    PubMed

    Angelopoulou, Matina V; Kontogiorgos, Elias; Emmanouil, Dimitris

    2015-06-01

    Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive disorder characterized by insufficient production of cortisol. The aim of this case report was to present a child with CAH, premature exfoliation of primary teeth and accelerated eruption of his permanent teeth related to bone resorption. A 4.5-year-old Caucasian boy with CAH and long-term administration of glucocorticoids was referred for dental restoration. Clinical examination revealed primary molars with worn stainless steel crowns, severe attrition of the upper canines, and absence of the upper incisors. Before the completion of treatment, abnormal mobility of the first upper primary molars and the lower incisors was detected, and a few days later the teeth exfoliated prematurely. Histologic examination revealed normal tooth structure. Alkaline phosphatase and blood cells values were normal. Eruption of the permanent dentition was also accelerated. Tooth mobility was noticed in the permanent teeth as soon as they erupted, along with bone destruction. Examination revealed an elevated level of receptor activator of nuclear factor-κB ligand and lower-than-normal osteoprotegerin and vitamin D levels. The patient was treated with vitamin D supplements, and his teeth have been stable ever since. CAH is a serious chronic disorder appearing in children with accelerated dental development and possibly premature loss of primary teeth.

  7. Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

    PubMed Central

    Buttigliero, Consuelo; Fioramonti, Marco; Bertaglia, Valentina; Vincenzi, Bruno; Zoccoli, Alice; Ribelli, Giulia; Tucci, Marcello; Vignani, Francesca; Berruti, Alfredo; Scagliotti, Giorgio Vittorio; Tonini, Giuseppe; Santini, Daniele

    2015-01-01

    Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI. Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients. These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity. PMID:25904051

  8. Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

    PubMed Central

    Scheibel, Paula Cabrini; Ramos, Adilson Luiz; Iwaki, Lilian Cristina Vessoni; Micheletti, Kelly Regina

    2014-01-01

    OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI) and external apical root resorption (EARR) after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1) and after 12 months of treatment (T2). ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157). CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction. PMID:25715722

  9. Calcium enriched mixture cement for primary molars exhibiting root perforations and extensive root resorption: report of three cases.

    PubMed

    Tavassoli-Hojjati, Sara; Kameli, Somayeh; Rahimian-Emam, Sara; Ahmadyar, Maryam; Asgary, Saeed

    2014-01-01

    In primary molars with root perforations of endodontic origin, tooth extraction and space maintainer are recommended. Calcium-enriched mixture (CEM) cement is a new biomaterial demonstrating favorable sealability/biocompatibility. This report presents a novel treatment modality for cases of primary molar teeth with root perforations associated with a periodontal lesion due to extensive inflammatory root resorption, whereby CEM was used as a perforation repair/pulpotomy biomaterial. Three cases of primary molar root perforations due to inflammatory resorption were selected; all cases were associated with furcal lesions of endodontic origin. Pulp chambers were accessed/irrigated with NaOCl; the root canal orifices were filled with CEM and restored with stainless steel crowns. Clinical/radiographic examinations up to 17 months revealed that all teeth were functional and free of signs/symptoms of infection and all had complete bone healing. Further trials are suggested to confirm CEM use for management of root perforations in primary molars exhibiting root perforation.

  10. Quality of different gutta-percha techniques when filling experimental internal resorptive cavities: a micro-computed tomography study.

    PubMed

    Keles, Ali; Ahmetoglu, Fuat; Uzun, Ismail

    2014-12-01

    The purpose of this ex vivo study was to determine the quality of root fillings in experimental internal resorptive cavities filled using cold lateral condensation (CLC), vertical condensation and Thermafil techniques. Forty-five extracted maxillary canine teeth were selected. After root canal instrumentation, the roots were sectioned horizontally and experimental internal resorption cavities were prepared. The root sections were re-approximated with a luting agent and randomly assigned to three groups (n = 15) to be filled using CLC, vertical condensation and Thermafil, respectively. Assessment of obturation quality in the internal resorptive cavity was performed using a desktop X-ray micro focus computed tomography scanner, and the percentage of gutta-percha (GP), sealer and voiding was calculated for each specimen. Data were statistically analysed using non-parametric tests, with P < 0.05 denoting a statistically significant difference. Vertical condensation filled 96.25 ± 8.31% of the total artificial cavity, and was superior to CLC (63.20 ± 16.87%) and Thermafil (59.26 ± 18.47%). The mean percentage of voids was 3.75 ± 8.31% in the vertical condensation group, 37.09 ± 17.13% in the CLC group and 41.06 ± 18.60% in the Thermafil group. We conclude that obturation of experimental resorption cavities is significantly better when using vertical condensation than when using other GP-based techniques.

  11. Nitrogen and phosphorus additions alter nutrient dynamics but not resorption efficiencies of Chinese fir leaves and twigs differing in age.

    PubMed

    Chen, Fu-Sheng; Niklas, Karl Joseph; Liu, Yu; Fang, Xiang-Min; Wan, Song-Ze; Wang, Huimin

    2015-10-01

    It is unclear how or even if phosphorus (P) input alters the influence of nitrogen (N) deposition in a forest. In theory, nutrients in leaves and twigs differing in age may show different responses to elevated nutrient input. To test this possibility, we selected Chinese fir (Cunninghamia lanceolata) for a series of N and P addition experiments using treatments of +N1 - P (50 kg N ha(-1) year(-1)), +N2 - P (100 kg N ha(-1) year(-1)), -N + P (50 kg P ha(-1) year(-1)), +N1 + P, +N2 + P and -N - P (without N and P addition). Soil samples were analyzed for mineral N and available P concentrations. Leaves and twigs in summer and their litters in winter were classified as and sorted into young and old components to measure N and P concentrations. Soil mineral N and available P increased with N and P additions, respectively. Nitrogen addition increased leaf and twig N concentrations in the second year, but not in the first year; P addition increased leaf and twig P concentrations in both years and enhanced young but not old leaf and twig N accumulations. Nitrogen and P resorption proficiencies in litters increased in response to N and P additions, but N and P resorption efficiencies were not significantly altered. Nitrogen resorption efficiency was generally higher in leaves than in twigs and in young vs old leaves and twigs. Phosphorus resorption efficiency showed a minimal variation from 26.6 to 47.0%. Therefore, P input intensified leaf and twig N enrichment with N addition, leaf and twig nutrients were both gradually resorbed with aging, and organ and age effects depended on the extent of nutrient limitation.

  12. Application of virtual three-dimensional surgery planning in management of open bite with idiopathic condylar resorption

    PubMed Central

    Kau, Chung How; Bejemir, Morvarid Poorsattar

    2015-01-01

    This case report describes the successful treatment of an adult patient with idiopathic condylar resorption and Class II skeletal open bite malocclusion and temporomandibular joint disorder. A segmental Le Fort I bilateral osteotomy, ramus increasing length inverted L–osteotomy, and genioplasty combined with orthodontic treatment were performed. The treatment plan and surgery was aided by three-dimensional medical modeling, and we managed to resolve functional, esthetic, and pain concerns to a satisfactory level. PMID:26981482

  13. Nitrogen and phosphorus additions alter nutrient dynamics but not resorption efficiencies of Chinese fir leaves and twigs differing in age.

    PubMed

    Chen, Fu-Sheng; Niklas, Karl Joseph; Liu, Yu; Fang, Xiang-Min; Wan, Song-Ze; Wang, Huimin

    2015-10-01

    It is unclear how or even if phosphorus (P) input alters the influence of nitrogen (N) deposition in a forest. In theory, nutrients in leaves and twigs differing in age may show different responses to elevated nutrient input. To test this possibility, we selected Chinese fir (Cunninghamia lanceolata) for a series of N and P addition experiments using treatments of +N1 - P (50 kg N ha(-1) year(-1)), +N2 - P (100 kg N ha(-1) year(-1)), -N + P (50 kg P ha(-1) year(-1)), +N1 + P, +N2 + P and -N - P (without N and P addition). Soil samples were analyzed for mineral N and available P concentrations. Leaves and twigs in summer and their litters in winter were classified as and sorted into young and old components to measure N and P concentrations. Soil mineral N and available P increased with N and P additions, respectively. Nitrogen addition increased leaf and twig N concentrations in the second year, but not in the first year; P addition increased leaf and twig P concentrations in both years and enhanced young but not old leaf and twig N accumulations. Nitrogen and P resorption proficiencies in litters increased in response to N and P additions, but N and P resorption efficiencies were not significantly altered. Nitrogen resorption efficiency was generally higher in leaves than in twigs and in young vs old leaves and twigs. Phosphorus resorption efficiency showed a minimal variation from 26.6 to 47.0%. Therefore, P input intensified leaf and twig N enrichment with N addition, leaf and twig nutrients were both gradually resorbed with aging, and organ and age effects depended on the extent of nutrient limitation. PMID:26358049

  14. The response of macrophages to titanium particles is determined by macrophage polarization.

    PubMed

    Pajarinen, Jukka; Kouri, Vesa-Petteri; Jämsen, Eemeli; Li, Tian-Fang; Mandelin, Jami; Konttinen, Yrjö T

    2013-11-01

    Aseptic loosening of total joint replacements is driven by the reaction of macrophages to foreign body particles released from the implant. It was hypothesized that the macrophages' response to these particles is dependent, in addition to particle characteristics and contaminating biomolecules, on the state of macrophage polarization as determined by the local cytokine microenvironment. To test this hypothesis we differentiated M1 and M2 macrophages from human peripheral blood monocytes and compared their responses to titanium particles using genome-wide microarray analysis and a multiplex cytokine assay. In comparison to non-activated M0 macrophages, the overall chemotactic and inflammatory responses to titanium particles were greatly enhanced in M1 macrophages and effectively suppressed in M2 macrophages. In addition, the genome-wide approach revealed several novel, potentially osteolytic, particle-induced mediators, and signaling pathway analysis suggested the involvement of toll-like and nod-like receptor signaling in particle recognition. It is concluded that the magnitude of foreign body reaction caused by titanium particles is dependent on the state of macrophage polarization. Thus, by limiting the action of M1 polarizing factors, e.g. bacterial biofilm formation, in peri-implant tissues and promoting M2 macrophage polarization by biomaterial solutions or pharmacologically, it might be possible to restrict wear-particle-induced inflammation and osteolysis.

  15. Inhibitory effects of French pine bark extract, Pycnogenol®, on alveolar bone resorption and on the osteoclast differentiation.

    PubMed

    Sugimoto, Hideki; Watanabe, Kiyoko; Toyama, Toshizo; Takahashi, Shun-suke; Sugiyama, Shuta; Lee, Masaichi-Chang-il; Hamada, Nobushiro

    2015-02-01

    Pycnogenol(®) (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non-infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate-resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1-100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis.

  16. Anti-inflammatory and Anti-resorptive Effects of Atorvastatin on Alveolar Bone Loss in Wistar Rats.

    PubMed

    Goes, Paula; Lima, Neiberg Alcântara; Rodrigues, José Ariévilo Gurgel; Benevides, Norma Maria Barros; Brito, Gerly Anne Castro; Lima, Vilma

    2016-01-01

    The aim of this study was to evaluate the anti-inflammatory and anti-resorptive effect of atorvastatin (ATV) in an experimental alveolar bone loss (ABL) model. Wistar rats were subjected to ligature placement around the maxillary second molar for 11 days. The animals received 0.9% saline (2 mL/kg) or ATV (0.3, 3 or 27 mg/kg) daily by gavage. ABL was evaluated by resorption area and histopathological analysis. Serum bone-specific alkaline phosphatase (BALP) activity was also evaluated. Leukogram was performed at 0 h, 6th h, 2nd, 7th and 11th days. Kidney and liver conditions and the body mass variation were analyzed. ATV (3 and 27 mg/kg) inhibited ABL by 39% and 56%, respectively. Histopathological analysis showed that ATV 27 mg/kg prevented ABL and cemental resorption, and inflammatory cell infiltration induced by ligature. ATV (27 mg/kg) prevented serum BALP levels reduction. ATV (27 mg/kg) prevented leukocytosis and did not affect either kidney or liver function nor body mass weight. ATV showed a protecting effect in the ligature-induced periodontitis, without affecting system parameters, by inhibition of inflammatory process and by its anabolic activity on the alveolar bone. PMID:27224558

  17. Effect of placement of occlusive membranes on root resorption and bone regeneration during healing of circumferential periodontal defects in dogs.

    PubMed

    Claffey, N; Hahn, R; Egelberg, J

    1989-07-01

    Previous studies indicate that root resorption is a frequent sequela to significant amounts of periodontal repair in animal models. A model was developed in labrador dogs to study periodontal wound healing in large circumferential defects in the absence of influence from the oral environment. A polytetrafluorethylene membrane of 1 micron pore size (GORE-TEX) was used to occlude cells from specific tissues from populating the healing dentin-connective tissue wound. 3 modalities were studied: (1) control, in which no membrane and therefore no cell occlusion was used, (2) flap occlusion, in which the internal surface of the flap was lined with the membrane preventing contribution of cells from the flap, (3) bone occlusion, in which the reduced alveolar bone was lined with the membrane preventing contribution from bone cells. Wound closure included total submergence of teeth and membranes. The membranes remained incorporated and no exposure of membranes or teeth occurred during the 3 months healing period. Histology revealed bone regrowth in all 3 treatment modalities. It is suggested that inductive elements in the connective tissue or dentin, or bone cells from periosteum were responsible for bone regrowth in the bone membrane treatment modality. No significant difference was seen for root resorption between the 3 treatment modalities. This study found that physical occlusion of cells from the inside of the surgical flap, or from the pre-existing bone, is not sufficient to prevent root resorption in periodontal wound healing.

  18. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo.

    PubMed Central

    Garrett, I R; Boyce, B F; Oreffo, R O; Bonewald, L; Poser, J; Mundy, G R

    1990-01-01

    The mechanisms by which bone resorbing osteoclasts form and are activated by hormones are poorly understood. We show here that the generation of oxygen-derived free radicals in cultured bone is associated with the formation of new osteoclasts and enhanced bone resorption, identical to the effects seen when bones are treated with hormones such as parathyroid hormone (PTH) and interleukin 1 (IL-1). When free oxygen radicals were generated adjacent to bone surfaces in vivo, osteoclasts were also formed. PTH and IL-1-stimulated bone resorption was inhibited by both natural and recombinant superoxide dismutase, an enzyme that depletes tissues of superoxide anions. We used the marker nitroblue tetrazolium (NBT) to identify the cells that were responsible for free radical production in resorbing bones. NBT staining was detected only in osteoclasts in cultures of resorbing bones. NBT staining in osteoclasts was decreased in bones coincubated with calcitonin, an inhibitor of bone resorption. We also found that isolated avian osteoclasts stained positively for NBT. NBT staining in isolated osteoclasts was increased when the cells were incubated with bone particles, to which they attach. We confirmed the formation of superoxide anion in isolated avian osteoclasts using ferricytochrome c reduction as a method of detection. The reduction of ferricytochrome c in isolated osteoclasts was inhibited by superoxide dismutase. Our results suggest that oxygen-derived free radicals, and particularly the superoxide anion, are intermediaries in the formation and activation of osteoclasts. Images PMID:2312718

  19. Stimulation of a Gs-like G protein in the osteoclast inhibits bone resorption but enhances tartrate-resistant acid phosphatase secretion.

    PubMed

    Moonga, B S; Pazianas, M; Alam, A S; Shankar, V S; Huang, C L; Zaidi, M

    1993-01-29

    Previous studies have demonstrated that G-protein agonists induce quiescence (Q effect) or retraction (R effect) in isolated osteoclasts. We now report the functional effects of such agonists on osteoclastic bone resorption and enzyme release. Exposure of osteoclasts to tetrafluoro-aluminate anions (AlF4-), a universal G protein stimulator, resulted in a marked concentration-dependent inhibition of bone resorption. This was associated with a dramatic increase in the secretion of the osteoclast-specific enzyme, tartrate-resistant acid phosphatase (TRAP). Cholera toxin, a Gs stimulator and a selective Q effect agonist, similarly abolished bone resorption and enhanced TRAP secretion. In contrast, pertussis toxin, a Gi inhibitor and a selective R effect agonist, inhibited bone resorption significantly, but slightly reduced enzyme release. The results suggest an involvement of a Gs-like G protein in TRAP secretion from the osteoclast, possibly through a cyclic AMP-dependent mechanism.

  20. Macrophages in Vascular Inflammation: Origins and Functions.

    PubMed

    Decano, Julius L; Mattson, Peter C; Aikawa, Masanori

    2016-06-01

    Macrophages influence various processes of cardiovascular inflammation. Whether they are of embryonic or post-natal hematopoietic origin, their balance in differential activation may direct the course of inflammation. Accelerated macrophage activation and accumulation through a pro-inflammatory signaling pathway may result in extensive tissue damage, adverse repair, and worsened clinical outcomes. Attenuation of such a mechanism and/or promotion of the anti-inflammatory macrophage activation may lead to early resolution of inflammation. Elucidating multiple novel mechanisms of monocyte and macrophage activation leads to a better understanding of their roles in vascular inflammation. In turn, this begets better therapeutic target identification and biomarker discovery. Combined with increasingly sensitive and specific imaging techniques, we continue to push back early detection and monitoring to provide us with a greater window for disease modification. The potential success of cytokine-targeted therapy will be solid proof of the inflammatory hypothesis of atherothrombosis. PMID:27125207

  1. Amphibian macrophage development and antiviral defenses.

    PubMed

    Grayfer, Leon; Robert, Jacques

    2016-05-01

    Macrophage lineage cells represent the cornerstone of vertebrate physiology and immune defenses. In turn, comparative studies using non-mammalian animal models have revealed that evolutionarily distinct species have adopted diverse molecular and physiological strategies for controlling macrophage development and functions. Notably, amphibian species present a rich array of physiological and environmental adaptations, not to mention the peculiarity of metamorphosis from larval to adult stages of development, involving drastic transformation and differentiation of multiple new tissues. Thus it is not surprising that different amphibian species and their respective tadpole and adult stages have adopted unique hematopoietic strategies. Accordingly and in order to establish a more comprehensive view of these processes, here we review the hematopoietic and monopoietic strategies observed across amphibians, describe the present understanding of the molecular mechanisms driving amphibian, an in particular Xenopus laevis macrophage development and functional polarization, and discuss the roles of macrophage-lineage cells during ranavirus infections.

  2. Macrophage diversity in renal injury and repair

    PubMed Central

    Ricardo, Sharon D.; van Goor, Harry; Eddy, Allison A.

    2008-01-01

    Monocyte-derived macrophages can determine the outcome of the immune response and whether this response contributes to tissue repair or mediates tissue destruction. In addition to their important role in immune-mediated renal disease and host defense, macrophages play a fundamental role in tissue remodeling during embryonic development, acquired kidney disease, and renal allograft responses. This review summarizes macrophage phenotype and function in the orchestration of kidney repair and replacement of specialized renal cells following injury. Recent advances in our understanding of macrophage heterogeneity in response to their microenvironment raise new and exciting therapeutic possibilities to attenuate or conceivably reverse progressive renal disease in the context of fibrosis. Furthermore, parallels with pathological processes in many other organs also exist. PMID:18982158

  3. Generation and Characterization of Mouse Regulatory Macrophages.

    PubMed

    Carretero-Iglesia, Laura; Hill, Marcelo; Cuturi, Maria Cristina

    2016-01-01

    In the last years, cell therapy has become a promising approach to therapeutically manipulate immune responses in autoimmunity, cancer, and transplantation. Several types of lymphoid and myeloid cells origin have been generated in vitro and tested in animal models. Their efficacy to decrease pharmacological treatment has successfully been established. Macrophages play an important role in physiological and pathological processes. They represent an interesting cell population due to their high plasticity in vivo and in vitro. Here, we describe a protocol to differentiate murine regulatory macrophages in vitro from bone marrow precursors. We also describe several methods to assess macrophage classical functions, as their bacterial killing capacity and antigen endocytosis and degradation. Importantly, regulatory macrophages also display suppressive characteristics, which are addressed by the study of their hypostimulatory T lymphocyte capacity and polyclonal T lymphocyte activation suppression.

  4. Trophic macrophages in development and disease

    PubMed Central

    Pollard, Jeffrey W.

    2013-01-01

    Specialized phagocytes are found in the most primitive multicellular organisms. Their roles in homeostasis and in distinguishing self from non-self have evolved with the complexity of organisms and their immune systems. Equally important, but often overlooked, are the roles of macrophages in tissue development. As discussed in this Review, these include functions in branching morphogenesis, neuronal patterning, angiogenesis, bone morphogenesis and the generation of adipose tissue. In each case, macrophage depletion impairs the formation of the tissue and compromises its function. I argue that in several diseases, the unrestrained acquisition of these developmental macrophage functions exacerbates pathology. For example, macrophages enhance tumour progression and metastasis by affecting tumour-cell migration and invasion, as well as angiogenesis. PMID:19282852

  5. Senescence and quiescence induced compromised function in cultured macrophages.

    PubMed

    Holt, Dolly J; Grainger, David W

    2012-10-01

    Implants are predisposed to infection even years after implantation, despite ostensibly being surrounded by innumerable macrophages as part of the host foreign body response. The local implant environment could adversely influence the implant-associated macrophage phenotype, proliferative capacity, activation states, and ability to neutralize pathogens. This study monitored cultured macrophage proliferative states and phagocytotic competence on tissue culture plastic to address the hypothesis that extended contact with foreign materials alters macrophage phenotype. That such macrophage alterations might also occur around implants has significance to the foreign body response, infection, cancer, autoimmune and other diseases. Specifically, multiple indicators of macrophage proliferation in various culture conditions, including cell confluence, long-term culture (21 days), lipopolysaccharide (LPS) stimulation, passaging, and mitogenic stimulation are reported. Importantly, primary murine macrophages became quiescent at high confluence and senescent during long-term culture. Senescent macrophages significantly reduced their ability to phagocytose particles, while quiescent macrophages did not. Cell senescence and quiescence were not observed with repeated passaging. Primary macrophage stimulation with LPS delayed senescence but did not eliminate it. These results prompt the conclusion that both cell quiescence and senescence are observed under common macrophage culture conditions and could alter macrophage behavior and phenotypes in extended in vitro culture, such as the ability to phagocytose. Such macrophage transitions around foreign bodies in vivo are not documented: quiescence and senescence reported here in macrophage culture could be relevant to macrophage behavior both in vitro in bioassays and in vivo in the foreign body response and implant-centered infection.

  6. Imaging macrophages in trehalose with SIMS

    NASA Astrophysics Data System (ADS)

    Parry, S. A.; Kurczy, M. E.; Fan, X.; Halleck, M. S.; Schlegel, R. A.; Winograd, N.

    2008-12-01

    Phagocytosis is a major component of the animal immune system where apoptotic cellular material, metabolites, and waste are safely processed. Further, efficient phagocytosis by macrophages is key to maintaining healthy vascular systems and preventing atherosclerosis. Single-cell images of macrophage phagocytosis of red blood cells, RBCs, and polystyrene microspheres have been chemically mapped with TOF-SIMS. We demonstrate here cholesterol and phosphocholine localizations as relative to time and activity.

  7. The Many Alternative Faces of Macrophage Activation

    PubMed Central

    Hume, David A.

    2015-01-01

    Monocytes and macrophages provide the first line of defense against pathogens. They also initiate acquired immunity by processing and presenting antigens and provide the downstream effector functions. Analysis of large gene expression datasets from multiple cells and tissues reveals sets of genes that are co-regulated with the transcription factors that regulate them. In macrophages, the gene clusters include lineage-specific genes, interferon-responsive genes, early inflammatory genes, and genes required for endocytosis and lysosome function. Macrophages enter tissues and alter their function to deal with a wide range of challenges related to development and organogenesis, tissue injury, malignancy, sterile, or pathogenic inflammatory stimuli. These stimuli alter the gene expression to produce “activated macrophages” that are better equipped to eliminate the cause of their influx and to restore homeostasis. Activation or polarization states of macrophages have been classified as “classical” and “alternative” or M1 and M2. These proposed states of cells are not supported by large-scale transcriptomic data, including macrophage-associated signatures from large cancer tissue datasets, where the supposed markers do not correlate with other. Individual macrophage cells differ markedly from each other, and change their functions in response to doses and combinations of agonists and time. The most studied macrophage activation response is the transcriptional cascade initiated by the TLR4 agonist lipopolysaccharide. This response is reviewed herein. The network topology is conserved across species, but genes within the transcriptional network evolve rapidly and differ between mouse and human. There is also considerable divergence in the sets of target genes between mouse strains, between individuals, and in other species such as pigs. The deluge of complex information related to macrophage activation can be accessed with new analytical tools and new databases

  8. Macrophages modulate adult zebrafish tail fin regeneration.

    PubMed

    Petrie, Timothy A; Strand, Nicholas S; Yang, Chao-Tsung; Tsung-Yang, Chao; Rabinowitz, Jeremy S; Moon, Randall T

    2014-07-01

    Neutrophils and macrophages, as key mediators of inflammation, have defined functionally important roles in mammalian tissue repair. Although recent evidence suggests that similar cells exist in zebrafish and also migrate to sites of injury in larvae, whether these cells are functionally important for wound healing or regeneration in adult zebrafish is unknown. To begin to address these questions, we first tracked neutrophils (lyzC(+), mpo(+)) and macrophages (mpeg1(+)) in adult zebrafish following amputation of the tail fin, and detailed a migratory timecourse that revealed conserved elements of the inflammatory cell response with mammals. Next, we used transgenic zebrafish in which we could selectively ablate macrophages, which allowed us to investigate whether macrophages were required for tail fin regeneration. We identified stage-dependent functional roles of macrophages in mediating fin tissue outgrowth and bony ray patterning, in part through modulating levels of blastema proliferation. Moreover, we also sought to detail molecular regulators of inflammation in adult zebrafish and identified Wnt/β-catenin as a signaling pathway that regulates the injury microenvironment, inflammatory cell migration and macrophage phenotype. These results provide a cellular and molecular link between components of the inflammation response and regeneration in adult zebrafish. PMID:24961798

  9. Immunological characterization of pulmonary intravascular macrophages

    NASA Technical Reports Server (NTRS)

    Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

  10. Cyclosporine inhibits macrophage-mediated antigen presentation

    SciTech Connect

    Ziegler, H.K.; Palay, D.; Wentworth, P.; Cluff, C.

    1986-03-01

    The influence of cyclosporine on antigen-specific, macrophage-dependent T cell activation was analyzed in vitro. Murine T cell activation by antigens derived from Listeria monocytogenes was monitored by the production of interleukin-2. Pretreatment (2 hrs., 37/sup 0/C) of macrophages with cyclosporine resulted in a population of macrophages with a markedly diminished capacity to support the activation of T lymphocytes. When cyclosporine-pretreated macrophages were added to cultures of antigen and untreated T cells, the dose of cyclosporine which produced 50% inhibition was 1.5 ..mu..g/ml. Appropriate control experiments indicated that cyclosporine was indeed inhibiting at the macrophage level. The addition of interleukin-1 or indomethacin to the cultures did not alter the inhibitory effect of cyclosporine. Under conditions which produced >90% inhibition of antigen presentation, macrophage surface Ia expression was not altered, and the uptake and catabolism of radiolabelled antigen was normal. Thus, cyclosporine inhibits antigen presentation by a mechanism which appears unrelated to changes in Il-1 elaboration, prostaglandin production, Ia expression, or antigen uptake and catabolism.

  11. Macrophages - silent enemies in juvenile idiopathic arthritis.

    PubMed

    Świdrowska-Jaros, Joanna; Orczyk, Krzysztof; Smolewska, Elżbieta

    2016-07-06

    The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile idiopathic arthritis (JIA). The effect of macrophage action depends on the type of their activation. Classically activated macrophages (M1) are responsible for release of molecules crucial for joint inflammation. Alternatively activated macrophages (M2) may recognize self antigens by scavenger receptors and induce the immunological reaction leading to autoimmune diseases such as JIA. Molecules essential for JIA pathophysiology include: TNF-α, the production of which precedes synovial inflammation in rheumatoid arthritis; IL-1 as a key mediator of synovial damage; chemotactic factors for macrophages IL-8 and MCP-1; IL6, the level of which correlates with the radiological joint damage; MIF, promoting the secretion of TNF-α and IL-6; CCL20 and HIF, significant for the hypoxic synovial environment in JIA; GM-CSF, stimulating the production of macrophages; and IL-18, crucial for NK cell functions. Recognition of the role of macrophages creates the potential for a new therapeutic approach.

  12. Macrophage-mediated cholesterol handling in atherosclerosis.

    PubMed

    Chistiakov, Dimitry A; Bobryshev, Yuri V; Orekhov, Alexander N

    2016-01-01

    Formation of foam cells is a hallmark at the initial stages of atherosclerosis. Monocytes attracted by pro-inflammatory stimuli attach to the inflamed vascular endothelium and penetrate to the arterial intima where they differentiate to macrophages. Intimal macrophages phagocytize oxidized low-density lipoproteins (oxLDL). Several scavenger receptors (SR), including CD36, SR-A1 and lectin-like oxLDL receptor-1 (LOX-1), mediate oxLDL uptake. In late endosomes/lysosomes of macrophages, oxLDL are catabolysed. Lysosomal acid lipase (LAL) hydrolyses cholesterol esters that are enriched in LDL to free cholesterol and free fatty acids. In the endoplasmic reticulum (ER), acyl coenzyme A: cholesterol acyltransferase-1 (ACAT1) in turn catalyses esterification of cholesterol to store cholesterol esters as lipid droplets in the ER of macrophages. Neutral cholesteryl ester hydrolases nCEH and NCEH1 are involved in a secondary hydrolysis of cholesterol esters to liberate free cholesterol that could be then out-flowed from macrophages by cholesterol ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 and SR-BI. In atherosclerosis, disruption of lipid homoeostasis in macrophages leads to cholesterol accumulation and formation of foam cells. PMID:26493158

  13. Salmonella acquires ferrous iron from haemophagocytic macrophages.

    PubMed

    Nagy, Toni A; Moreland, Sarah M; Detweiler, Corrella S

    2014-09-01

    Bacteria harbour both ferrous and ferric iron transporters. We now report that infection of macrophages and mice with a Salmonella enterica Typhimurium strain containing an inactivated feoB-encoded ferrous iron transporter results in increased bacterial replication, compared to infection with wild type. Inactivation of other cation transporters, SitABCD or MntH, did not increase bacterial replication. The feoB mutant strain does not have an intrinsically faster growth rate. Instead, increased replication correlated with increased expression in macrophages of the fepB-encoded bacterial ferric iron transporter and also required siderophores, which capture ferric iron. Co-infection of mice with wild type and a feoB mutant strain yielded a different outcome: FeoB is clearly required for tissue colonization. In co-infected primary mouse macrophages, FeoB is required for S. Typhimurium replication if the macrophages were IFNγ treated and contain phagocytosed erythrocytes, a model for haemophagocytosis. Haemophagocytes are macrophages that have engulfed erythrocytes and/or leucocytes and can harbour Salmonella in mice. These observations suggest that Salmonella acquires ferrous iron from haemophagocytic macrophages.

  14. Endometriosis, a disease of the macrophage.

    PubMed

    Capobianco, Annalisa; Rovere-Querini, Patrizia

    2013-01-01

    Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularized endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone marrow-derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload) in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need.

  15. Endometriosis, a disease of the macrophage

    PubMed Central

    Capobianco, Annalisa; Rovere-Querini, Patrizia

    2013-01-01

    Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularized endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone marrow-derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload) in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need. PMID:23372570

  16. Effects of low-level laser therapy on orthodontic tooth movement and root resorption after artificial socket preservation

    PubMed Central

    Seifi, Massoud; Atri, Faezeh; Yazdani, Mohammad Masoud

    2014-01-01

    Background: Low- level laser therapy has been used to stimulate the orthodontic tooth movements (OTM) previously. Furthermore, in the orthodontic treatments accompanying tooth extractions, the adjacent teeth move towards the extraction sites and close the space in some cases. Then, the adjacent tooth movements must be prevented in the treatments requiring space. Laser stimulates and at some doses decelerates tooth movement; it also improves healing process and enhances osteogenesis. Hence, it can prevent movement by osteogenesis adjacent to the tooth. The present study investigated the effects of low-level laser therapy on the OTM and root resorption following artificial socket preservation. Materials and Methods: In this experimental animal trial, 16 male albino rabbits were selected with similar characteristics and randomly divided in two groups. Under general anesthesia, an artificial socket, 8 mm in height, was created in the mesial aspect of the first premolars of the rabbits and filled with demineralized freeze dried bone allograft (DFDBA). The first premolars were connected to the incisors using nickel titanium coil springs. In experimental group, gallium-aluminum-arsenide (GaAlAs) laser was irritated mesial to first premolar where artificial socket was created continuously (808 nm). The cycle was 10 days irritation, 14 days rest, 10 days irritation, 14 days rest (Biostimulation mode). Control group was not laser irradiated. All animals were sacrificed after 48 days and the distance between the distal aspect of the first premolars, and the mesial surface of the second premolars was measured with leaf gauge. The specimens underwent histological assessments. Integrity of root and its resorption was observed under microscope calibration. The size of resorption lacunae was calculated in mm2. Normality of data was proved according to Kolmogorov-Smirnov analysis, and Student's t-test was done. P value less than 0.05 was considered as significant. Results: The mean

  17. Management of bilateral invasive cervical resorption lesions in maxillary incisors using a novel calcium silicate-based cement: A case report.

    PubMed

    Karypidou, Athanasia; Chatzinikolaou, Ino-Dimitra; Kouros, Pantelis; Koulaouzidou, Elisabeth; Economides, Nikolaos

    2016-01-01

    Invasive cervical resorption is a pathologic process leading to progressive and usually destructive loss of tooth structure. The pathogenic mechanism is not completely understood and the diagnosis may be challenging. The aim of this article is to present an unusual case of bilateral presence of invasive cervical resorption lesions in maxillary central incisors and to discuss the treatment procedures using a novel repair material. The management of the present case was carried out in three phases. The first stage of the treatment aimed at curetting the active tissue from the resorption cavity and restoring the defect with the novel calcium silicate-based cement (Biodentine, Septodont). In the maxillary left central incisor it was not possible to remove the resorptive tissue without exposing the pulp, and therefore root canal treatment was performed. At the second phase, a full-thickness flap was raised in order to expose and repair the defect that was extending subgingivally. At the third phase teeth were restored with composite resin. The patient was kept under review and after a follow-up period of 2 years neither signs of periradicular lesion nor recurrence of resorption were observed. The teeth were asymptomatic, and restorations appeared to be in excellent condition. In conclusion, Biodentine seems to be a promising material for the treatment of invasive cervical resorption lesions. PMID:27341468

  18. Cortical bone resorption rate in elderly persons: Estimates from long-term in vivo measurements of 90Sr in the skeleton

    SciTech Connect

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2012-06-01

    The rate of cortical bone resorption was assessed from long-term in vivo measurements of 90Sr content in the skeleton for men aged 50-80 years and for women 0-30 years after menopause. Measurements of 90Sr were conducted with a whole body counter for residents of the Techa Riverside communities (Southern Urals, Russia), who ingested large amounts of 90Sr as a result of releases of liquid radioactive wastes into the river from the Mayak plutonium facility in early 1950s. The results of this study showed an increase in the rate of cortical bone resorption in both men and women, as based on the use of accidentally ingested 90Sr as a tracer for bone metabolism. In men there was a continuous gradual increase in the rate of cortical bone resorption after 55 years from 2.8 to 4.5%/year by the age of 75 years. In women, there was a doubled increase in the rate of cortical bone resorption after menopause of up to 6%/year; then the rate remained unchanged for 10-12 years with a subsequent gradual decline down to 5-5.5%/year. Comparison of the rate of cortical bone resorption in men and women older than 55 years showed that women expressed significantly higher levels of cortical bone resorption.

  19. Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

    SciTech Connect

    Deng Xue; Tamai, Riyoko; Endo, Yasuo; Kiyoura, Yusuke

    2009-02-15

    Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.

  20. Erythrina variegata extract exerts osteoprotective effects by suppression of the process of bone resorption.

    PubMed

    Zhang, Yan; Li, Qi; Li, Xiaoli; Wan, Hoi-Ying; Wong, Man-Sau

    2010-10-01

    Our previous study showed that Erythrina variegata L. (EV) inhibited bone loss and improved bone properties in ovariectomised rats. The purpose of the present study is to investigate the potential mechanism involved in mediating the osteoprotective actions of EV. Female Sprague-Dawley rats were fed a phyto-oestrogen-free diet and subjected to either ovariectomy or a sham operation. Ovariectomised rats were treated with genistein (40 mg/kg) as well as low (200 mg/kg), medium (500 mg/kg) or high (1000 mg/kg) doses of EV extract. Bone properties and mRNA expressions were evaluated by micro-computed tomography and quantitative RT-PCR, respectively. Osteoclast differentiation in RAW 264.7 cells was studied by tartrate-resistant acid phosphatase (TRAP) staining. High doses of EV could decrease urinary Ca and P excretion, maintain serum Ca and P level, and exert beneficial effects on the micro-structure and morphology of trabecular bone and cortical bone in ovariectomised rats. EV suppressed the up-regulation of cathepsin K mRNA and the down-regulation of osteoprotegrin mRNA in the tibia of ovariectomised rats. TRAP-positive cell numbers were significantly decreased in receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW 264.7 cells when co-cultured with EV extracts. The present study indicated that the protective effects of EV on bone properties in ovariectomised rats are likely to be mediated by its inhibitory actions on the process of bone resorption via the suppression of osteoclast differentiation and maturation. PMID:20487580

  1. Cellular and extracellular factors in early root resorption repair in the rat.

    PubMed

    Jäger, Andreas; Kunert, Dominique; Friesen, Therese; Zhang, Dongliang; Lossdörfer, Stefan; Götz, Werner

    2008-08-01

    The aim of this study was to investigate the role of extracellular matrix components, such as collagen type I, fibronectin, and osteopontin (OPN) during cementum repair following experimentally induced tooth movement, and to characterize the cells taking part in the regenerative process. The upper right first molars were moved mesially in 21 three-month-old male Wistar rats using a coil spring with a force of 0.5 N. After 9 days, the appliance was removed and the animals were killed in groups of three immediately after withdrawal of the force and 5, 7, 10, 12, 14, and 17 days later. Three rats served as non-experimental control animals. The maxillae were prepared and processed for histological analysis. Together with the disappearance of the multinucleated odontoclasts from the resorption lacunae, signs of repair were visible 5 days after the release of the orthodontic force. The first signs of cementum repair were seen on day 10. The newly produced cementum was of the acellular extrinsic fibre type (AEFC) and reattachment was achieved with the principal periodontal ligament (PDL) fibres orientated almost perpendicular to the root surface. The initial interface formed between the old and new cementum, as well as the new AEFC, was characterized by a strong immunoreaction with OPN and collagen I antibody, but only a weak immunoreaction with the fibronectin antibody. Only a small number of mononuclear cells, which were involved in the repair process, showed a positive immunoreaction with the osteoblastic lineage markers runt-related transcription factor 2 and osteocalcin. These same cells stained sparsely with muscle segment homeobox homologue 2, but not with the E11 antibody. Thus, most of the cells associated with this reparative activity on the surface of the lacunae were differentiated PDL cells of the fibroblastic phenotype. Cells with a defined osteoblastic phenotype seemed to be of minor importance in this repair process. PMID:18632841

  2. Residence, resorption and recycling of zircons in Devils Kitchen rhyolite, Coso Volcanic Field, California

    USGS Publications Warehouse

    Miller, J.S.; Wooden, J.L.

    2004-01-01

    Zircons from the Devils Kitchen rhyolite in the Pleistocene Coso Volcanic field, California have been analyzed by in situ Pb/U ion microprobe (SHRIMP-RG) and by detailed cathodoluminescence imaging. The zircons yield common-Pb-corrected and disequilibrium-corrected 206Pb/238U ages that predate a previously reported K-Ar sanidine age by up to 200 kyr, and the range of ages exhibited by the zircons is also approximately 200 kyr. Cathodoluminescence imaging indicates that zircons formed in contrasting environments. Most zircons are euhedral, and a majority of the zircons are weakly zoned, but many also have anhedral, embayed cores, with euhedral overgrowths and multiple internal surfaces that are truncated by later crystal zones. Concentrations of U and Th vary by two orders of magnitude within the zircon population, and by 10-20 times between zones within some zircon crystals, indicating that zircons were transferred between contrasting chemical environments. A zircon saturation temperature of ???750??C overlaps within error a previously reported phenocryst equilibration temperature of 740 ?? 25??C. Textures in zircons indicative of repeated dissolution and subsequent regrowth are probably caused by punctuated heating by mafic magma input into rhyolite. The overall span of ages and large variation in U and Th concentrations, combined with calculated zircon saturation temperatures and resorption times, are most compatible with crystallization in magma bodies that were emplaced piecemeal in the crust at Coso over 200 kyr prior to eruption, and that were periodically rejuvenated or melted by subsequent basaltic injections. ?? Oxford University Press 2004; all rights reserved.

  3. Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats.

    PubMed

    Turner, R T; Wakley, G K; Hannon, K S; Bell, N H

    1988-03-01

    The effects of the nonsteroidal antiestrogen tamoxifen were determined on trabecular bone mass in the proximal tibial metaphysis of intact and ovariectomized rats. Rats were ovariectomized at the beginning of the study. On day 7 of the study, 5-mg slow release pellets of tamoxifen or placebo were implanted sc. All of the rats were killed on day 28 of the experiment. Sections of the proximal tibial metaphysis were stained for acid phosphatase and evaluated histomorphometrically. Ovariectomy resulted in marked loss of bone. Compared to the values in sham-operated animals, the trabecular bone at a sampling site in the secondary spongiosa of ovariectomized rats was reduced by more than 60%, the length of trabecular bone surface covered by osteoclasts was increased by 563%, the percentage of trabecular bone surface covered by osteoclasts was increased by 567%, the mean osteoclast size was increased by 84%, and the number of nuclei per osteoclast was increased by 38%. In contrast, treatment of ovariectomized rats for 3 weeks with tamoxifen restored the histomorphometric measurements to values comparable to those in sham-operated animals. 17 beta-Estradiol increased trabecular bone fractional area in ovariectomized and sham-operated rats, and administration of tamoxifen to estrogen-treated, ovariectomized, and sham-operated animals produced a further increase in trabecular bone. In summary, 1) ovariectomy resulted in large increases in both the number and activity of osteoclasts, 2) the increased bone resorption associated with ovariectomy produced a net loss of trabecular bone, and 3) treatment of ovariectomized rats with tamoxifen prevented these skeletal changes. The results indicate that in the rat, tamoxifen mimics the effects of estrogen on trabecular bone at concentrations that are not uterotropic.

  4. Colonic macrophage polarization in homeostasis, inflammation, and cancer.

    PubMed

    Isidro, Raymond A; Appleyard, Caroline B

    2016-07-01

    Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed.

  5. Macrophage iron homeostasis and polarization in the context of cancer.

    PubMed

    Jung, Michaela; Mertens, Christina; Brüne, Bernhard

    2015-02-01

    Macrophages are central in regulating iron homeostasis, which is tightly linked to their versatile role during innate immunity. They sequester iron by phagocytosis of senescent erythrocytes and represent a major source of available iron in the body. Macrophage iron homeostasis is coupled to the functional heterogeneity and plasticity of these cells, with their extreme roles during inflammation, immune modulation, and resolution of inflammation. It is now appreciated that the macrophage polarization process dictates expression profiles of genes involved in iron metabolism. Therefore, macrophages have evolved a multitude of mechanisms to sequester, transport, store, and release iron. A new, enigmatic protein entering the iron scene and affecting the macrophage phenotype is lipocalin-2. Iron sequestration in macrophages depletes the microenvironment, thereby limiting extracellular pathogen or tumor growth, while fostering inflammation. In contrast, iron release from macrophages contributes to bystander cell proliferation, which is important for tissue regeneration and repair. This dichotomy is also reflected by the dual role of lipocalin-2 in macrophages. Unfortunately, the iron release macrophage phenotype is also a characteristic of tumor-associated macrophages and stimulates tumor cell survival and growth. Iron sequestration versus its release is now appreciated to be associated with the macrophage polarization program and can be used to explain a number of biological functions attributed to distinct macrophage phenotypes. Here we discuss macrophage iron homeostasis with a special focus on lipocalin-2 related to the formation and function of tumor-associated macrophages.

  6. Mannheimia haemolytica and Its Leukotoxin Cause Macrophage Extracellular Trap Formation by Bovine Macrophages

    PubMed Central

    Aulik, Nicole A.; Hellenbrand, Katrina M.

    2012-01-01

    Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen Mannheimia haemolytica and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to M. haemolytica or its LKT. Both native fully active LKT and noncytolytic pro-LKT (produced by an lktC mutant of M. haemolytica) stimulated MET formation. Confocal and scanning electron microscopy revealed a network of DNA fibrils with colocalized histones in extracellular traps released from bovine macrophages. Formation of METs required NADPH oxidase activity, as previously demonstrated for NET formation. METs formed in response to LKT trapped and killed a portion of the M. haemolytica cells. Bovine alveolar macrophages, but not peripheral blood monocytes, also formed METs in response to M. haemolytica cells. MET formation was not restricted to bovine macrophages. We also observed MET formation by the mouse macrophage cell line RAW 264.7 and by human THP-1 cell-derived macrophages, in response to Escherichia coli hemolysin. The latter is a member of the repeats-in-toxin (RTX) toxin family related to the M. haemolytica leukotoxin. This study demonstrates that macrophages, like neutrophils, can form extracellular traps in response to bacterial pathogens and their exotoxins. PMID:22354029

  7. Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro

    NASA Technical Reports Server (NTRS)

    Nguyen, Hal X.; Tidball, James G.

    2003-01-01

    Current evidence indicates that the physiological functions of inflammatory cells are highly sensitive to their microenvironment, which is partially determined by the inflammatory cells and their potential targets. In the present investigation, interactions between neutrophils, macrophages and muscle cells that may influence muscle cell death are examined. Findings show that in the absence of macrophages, neutrophils kill muscle cells in vitro by superoxide-dependent mechanisms, and that low concentrations of nitric oxide (NO) protect against neutrophil-mediated killing. In the absence of neutrophils, macrophages kill muscle cells through a NO-dependent mechanism, and the presence of target muscle cells causes a three-fold increase in NO production by macrophages, with no change in the concentration of inducible nitric oxide synthase. Muscle cells that are co-cultured with both neutrophils and macrophages in proportions that are observed in injured muscle show cytotoxicity through a NO-dependent, superoxide-independent mechanism. Furthermore, the concentration of myeloid cells that is necessary for muscle killing is greatly reduced in assays that use mixed myeloid cell populations, rather than uniform populations of neutrophils or macrophages. These findings collectively show that the magnitude and mechanism of muscle cell killing by myeloid cells are modified by interactions between muscle cells and neutrophils, between muscle cells and macrophages and between macrophages and neutrophils.

  8. Probiotic Bacillus amyloliquefaciens mediate M1 macrophage polarization in mouse bone marrow-derived macrophages.

    PubMed

    Ji, Jian; Hu, Sheng-Lan; Cui, Zhi-Wen; Li, Wei-Fen

    2013-05-01

    Depending on the microenvironment, macrophages can acquire distinct functional phenotypes, referred to as classically activated M1 and M2. M1 macrophages are considered potent effector cells that kill intracellular pathogens, and M2 macrophages promote the resolution of wound healing. In this study, we are interested to know whether probiotic Bacillus amyloliquefaciens (Ba) can induce macrophages polarization. Real-time fluorescence PCR analysis demonstrated that the expression of IL-1β, iNOS, TNF-α and IL-6 genes for M1 macrophages was significantly increased at 1.5 h after probiotic Ba treatment compared to the probiotic Ba-free treatment (P < 0.01), whereas the expression of M2 macrophage marker genes (Arg1, Fizz1, MR, Ym1) was decreased (P < 0.05). Furthermore, the phagocytic activity was dramatically increased in the Ba-treated BMDMs using a FITC-dextran endocytosis assay. Together, these findings indicated that probiotic Ba facilitated polarization of M1 macrophages and enhanced its phagocytic capacity. The results expanded our knowledge about probiotic function-involved macrophage polarization.

  9. Mannheimia haemolytica and its leukotoxin cause macrophage extracellular trap formation by bovine macrophages.

    PubMed

    Aulik, Nicole A; Hellenbrand, Katrina M; Czuprynski, Charles J

    2012-05-01

    Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen Mannheimia haemolytica and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to M. haemolytica or its LKT. Both native fully active LKT and noncytolytic pro-LKT (produced by an lktC mutant of M. haemolytica) stimulated MET formation. Confocal and scanning electron microscopy revealed a network of DNA fibrils with colocalized histones in extracellular traps released from bovine macrophages. Formation of METs required NADPH oxidase activity, as previously demonstrated for NET formation. METs formed in response to LKT trapped and killed a portion of the M. haemolytica cells. Bovine alveolar macrophages, but not peripheral blood monocytes, also formed METs in response to M. haemolytica cells. MET formation was not restricted to bovine macrophages. We also observed MET formation by the mouse macrophage cell line RAW 264.7 and by human THP-1 cell-derived macrophages, in response to Escherichia coli hemolysin. The latter is a member of the repeats-in-toxin (RTX) toxin family related to the M. haemolytica leukotoxin. This study demonstrates that macrophages, like neutrophils, can form extracellular traps in response to bacterial pathogens and their exotoxins. PMID:22354029

  10. Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

    NASA Technical Reports Server (NTRS)

    Globus, Ruth K.; Searby, Nancy D.; Almeida, Eduardo A. C.; Sutijono, Darrell; Yu, Joon-Ho; Malouvier, Alexander; Doty, Steven B.; Morey-Holton, Emily; Weinstein, Steven L.; Dalton, Bonnie P. (Technical Monitor)

    2000-01-01

    Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We

  11. Tyrosines 559 and 807 in the cytoplasmic tail of the macrophage colony-stimulating factor receptor play distinct roles in osteoclast differentiation and function.

    PubMed

    Feng, Xu; Takeshita, Sunao; Namba, Noriyuki; Wei, Shi; Teitelbaum, Steven L; Ross, F Patrick

    2002-12-01

    Osteoclast (OC) differentiation requires that precursors, such as macrophage colony-stimulating factor (M-CSF)-dependent bone marrow macrophages, receive signals transduced by receptor activator of nuclear factor kappaB (RANK) and c-Fms, receptors for RANK ligand (RANKL) and M-CSF, respectively. Activated c-Fms autophosphorylates cytoplasmic tail tyrosine residues, which, by recruiting adaptor molecules, initiate specific signaling pathways. To identify which tyrosine residues are involved in c-Fms signaling in primary cells, we retrovirally transduced M-CSF-dependent bone marrow macrophages with a chimera comprising the external domain of the erythropoietin (Epo) receptor linked to the transmembrane and cytoplasmic domains of c-Fms. Transduced cells differentiate into bone-resorbing osteoclasts when treated with RANKL and either M-CSF or Epo, confirming that both endogenous and chimeric receptors transmit osteoclastogenic signals. Cells expressing chimeric receptors with Y(697)F, Y(706)F, Y(721)F, and Y(921)F single point mutations generate normal numbers of bone-resorbing OCs, with normal bone-resorbing activity when treated with RANKL and Epo. In contrast, those expressing Y(559)F generate fewer OCs, whereas theY807F mutant is incapable of osteoclastogenesis. Finally, although mature OCs expressing Y(559)F exhibit impaired bone resorption, those bearing Y807F do not. Thus, we have identified specific tyrosine residues in the cytoplasmic tail of c-Fms that are critical for transmitting M-CSF-initiated signals individually required for OC formation or function, respectively.

  12. Macrophage Polarisation: an Immunohistochemical Approach for Identifying M1 and M2 Macrophages

    PubMed Central

    Barros, Mário Henrique M.; Hauck, Franziska; Dreyer, Johannes H.; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn’s disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool

  13. BMP pathway regulation of and by macrophages.

    PubMed

    Talati, Megha; West, James; Zaynagetdinov, Rinat; Hong, Charles C; Han, Wei; Blackwell, Tom; Robinson, Linda; Blackwell, Timothy S; Lane, Kirk

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a disease of progressively increasing pulmonary vascular resistance, associated with mutations of the type 2 receptor for the BMP pathway, BMPR2. The canonical signaling pathway for BMPR2 is through the SMAD family of transcription factors. BMPR2 is expressed in every cell type, but the impact of BMPR2 mutations affecting SMAD signaling, such as Bmpr2delx4+, had only previously been investigated in smooth muscle and endothelium. In the present study, we created a mouse with universal doxycycline-inducible expression of Bmpr2delx4+ in order to determine if broader expression had an impact relevant to the development of PAH. We found that the most obvious phenotype was a dramatic, but patchy, increase in pulmonary inflammation. We crossed these double transgenic mice onto an NF-κB reporter strain, and by luciferase assays on live mice, individual organs and isolated macrophages, we narrowed down the origin of the inflammatory phenotype to constitutive activation of tissue macrophages. Study of bone marrow-derived macrophages from mutant and wild-type mice suggested a baseline difference in differentiation state in Bmpr2 mutants. When activated with LPS, both mutant and wild-type macrophages secrete BMP pathway inhibitors sufficient to suppress BMP pathway activity in smooth muscle cells (SMC) treated with conditioned media. Functionally, co-culture with macrophages results in a BMP signaling-dependent increase in scratch closure in cultured SMC. We conclude that SMAD signaling through BMP is responsible, in part, for preventing macrophage activation in both live animals and in cells in culture, and that activated macrophages secrete BMP inhibitors in sufficient quantity to cause paracrine effect on vascular smooth muscle. PMID:24713633

  14. Cytolytic activity against tumor cells by macrophage cell lines and augmentation by macrophage stimulants.

    PubMed

    Taniyama, T; Holden, H T

    1980-07-15

    Previous studies have shown that macrophage cell lines retained the ability to phagocytize, to secrete lysosomal enzymes, and to function as effector cells in antibody-dependent cellular cytoxicity. In this paper, the cytolytic activity of murine macrophage cell lines against tumor target cells was assessed using an 18-h 51Cr release assay. Of the macrophage cell lines tested, RAW 264, PU5-1.8 and IC-21 had intermediate to high levels of spontaneous cytolytic activity, P388D, and J774 had low to intermediate levels, while /WEHI-3 showed little or no cytolytic activity against RBL-5, MBL-2 and TU-5 target cells. Tumor-cell killing by macrophage cell lines could be augmented by the addition of macrophage stimulants, such as bacterial lipopolysaccharide and poly I:C, indicating that the activation of macrophages by these stimulants does not require the participation of other cell types. Treatment with interferon also augmented the tumor-cell killing by macrophage cell lines. Although the mechanism by which these cell lines exert their spontaneous or boosted cytotoxic activity is not clear, it does not appear to be due to depletion of nutrients since cell lines with high metabolic and proliferative activities, such as WEHI-3 and RBL-5, showed little or no cytotoxicity and supernatants from the macrophage cell lines did not exert any cytotoxic effects in their essay. Thus, it appears that the different macrophage cell lines represent different levels of activation and/or differentiation and may be useful for studying the development of these processes as well as providing a useful tool for analyzing the mechanisms of macrophage-mediated cytolysis. PMID:6165690

  15. CD163 Identifies Perivascular Macrophages in Normal and Viral Encephalitic Brains and Potential Precursors to Perivascular Macrophages in Blood

    PubMed Central

    Kim, Woong-Ki; Alvarez, Xavier; Fisher, Jeanne; Bronfin, Benjamin; Westmoreland, Susan; McLaurin, JoAnne; Williams, Kenneth

    2006-01-01

    Perivascular macrophages are uniquely situated at the intersection between the nervous and immune systems. Although combined myeloid marker detection differentiates perivascular from resident brain macrophages (parenchymal microglia), no single marker distinguishes perivascular macrophages in humans and mice. Here, we present the macrophage scavenger receptor CD163 as a marker for perivascular macrophages in humans, monkeys, and mice. CD163 was primarily confined to perivascular macrophages and populations of meningeal and choroid plexus macrophages in normal brains and in brains of humans and monkeys with human immunodeficiency virus or simian immunodeficiency virus (SIV) encephalitis. Scattered microglia in SIV encephalitis lesions and multinucleated giant cells were also CD163 positive. Consistent with prior findings that perivascular macrophages are primary targets of human immunodeficiency virus and SIV, all SIV-infected cells in the brain were CD163 positive. Using fluorescent dyes that definitively and selectively label perivascular macrophages in vivo, we confirmed that dye-labeled simian perivascular macrophages were CD163 positive and able to repopulate the central nervous system within 24 hours. Flow cytometric studies demonstrated a subset of monocytes (CD163+CD14+CD16+) that were immunophenotypically similar to brain perivascular macrophages. These findings recognize CD163+ blood monocytes/macrophages as a source of brain perivascular macrophages and underscore the utility of this molecule in studying the biology of perivascular macrophages and their precursors in humans, monkeys, and mice. PMID:16507898

  16. Much More than M1 and M2 Macrophages, There are also CD169+ and TCR+ Macrophages

    PubMed Central

    Chávez-Galán, Leslie; Olleros, Maria L.; Vesin, Dominique; Garcia, Irene

    2015-01-01

    Monocytes are considered to be precursor cells of the mononuclear phagocytic system, and macrophages are one of the leading members of this cellular system. Macrophages play highly diverse roles in maintaining an organism’s integrity by either directly participating in pathogen elimination or repairing tissue under sterile inflammatory conditions. There are different subpopulations of macrophages and each one has its own characteristics and functions. In this review, we summarize present knowledge on the polarization of macrophages that allows the generation of subpopulations called classically activated macrophages or M1 and alternative activated macrophages or M2. Furthermore, there are macrophages that their origin and characterization still remain unclear but have bee