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Sample records for mononucleated macrophage resorption

  1. The Significance of Hemosiderin Deposition in the Lungs and Organs of the Mononucleated Macrophage Resorption System in Infants and Children

    PubMed Central

    Türkmen, Nursel; Fedakar, Recep; Akgöz, Semra

    2008-01-01

    Hemosiderin deposition is not often recognized on routine examination with hematoxylin and eosin staining; however, iron stains may be helpful in the evaluation of hemosiderin deposition in infant autopsies. This report describes the data obtained from autopsy of 86 infants and children whose deaths were investigated at the Forensic Medicine Council Bursa Morgue Department from January 2000 to January 2003. A histochemical technique was used to identify hemosiderin in lung, liver and spleen specimens, which was correlated with other descriptive variables such as the reported cause of death, postmortem interval, trauma history, gender, and age. There was a weakly positive but significant correlation between lung and liver hemosiderin scores (Spearman's rank correlation coefficient, rho=0.348, p=0.001); i.e., given an increase in lung hemosiderin scores, an increase in liver hemosiderin scores was also observed. Similarly, a marked positive correlation between spleen and liver hemosiderin scores (Spearman's rank correlation coefficient, rho=0.335, p=0.002) was observed. The probability of spleen hemosiderin-positive cases belonging to the age group under 6 months was found to be 4.3 times greater than those who were hemosiderin-negative (95% confidence interval, 1.6-11.8). After the major differential diagnoses were ruled out, this study demonstrated, that depending on the statistically assessed morphometric grounds, the presence of hemosiderin deposits in the liver and spleen were significantly higher in the age group under 6 months. PMID:19119447

  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. 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

  5. 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

  6. Mesenchymal Dental Pulp Cells Attenuate Dentin Resorption in Homeostasis

    PubMed Central

    Zheng, Y.; Chen, M.; He, L.; Marão, H.F.; Sun, D.M.; Zhou, J.; Kim, S.G.; Song, S.; Wang, S.L.

    2015-01-01

    Dentin in permanent teeth rarely undergoes resorption in development, homeostasis, or aging, in contrast to bone that undergoes periodic resorption/remodeling. The authors hypothesized that cells in the mesenchymal compartment of dental pulp attenuate osteoclastogenesis. Mononucleated and adherent cells from donor-matched rat dental pulp (dental pulp cells [DPCs]) and alveolar bone (alveolar bone cells [ABCs]) were isolated and separately cocultured with primary rat splenocytes. Primary splenocytes readily aggregated and formed osteoclast-like cells in chemically defined osteoclastogenesis medium with 20 ng/mL of macrophage colony-stimulating factor (M-CSF) and 50 ng/mL of receptor activator of nuclear factor κB ligand (RANKL). Strikingly, DPCs attenuated osteoclastogenesis when cocultured with primary splenocytes, whereas ABCs slightly but significantly promoted osteoclastogenesis. DPCs yielded ~20-fold lower RANKL expression but >2-fold higher osteoprotegerin (OPG) expression than donor-matched ABCs, yielding a RANKL/OPG ratio of 41:1 (ABCs:DPCs). Vitamin D3 significantly promoted RANKL expression in ABCs and OPG in DPCs. In vivo, rat maxillary incisors were atraumatically extracted (without any tooth fractures), followed by retrograde pulpectomy to remove DPCs and immediate replantation into the extraction sockets to allow repopulation of the surgically treated root canal with periodontal and alveolar bone–derived cells. After 8 wk, multiple dentin/root resorption lacunae were present in root dentin with robust RANKL and OPG expression. There were areas of dentin resoprtion alternating with areas of osteodentin formation in root dentin surface in the observed 8 wk. These findings suggest that DPCs of the mesenchymal compartment have an innate ability to attenuate osteoclastogenesis and that this innate ability may be responsible for the absence of dentin resorption in homeostasis. Mesenchymal attenuation of dentin resorption may have implications in internal

  7. 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

  8. 1α,25-Dihydroxyvitamin D3 inhibits the differentiation and bone resorption by osteoclasts generated from Wistar rat bone marrow-derived macrophages

    PubMed Central

    WANG, DONG; GU, JIAN-HONG; CHEN, YANG; ZHAO, HONG-YAN; LIU, WEI; SONG, RUI-LONG; BIAN, JIAN-CHUN; LIU, XUE-ZHONG; YUAN, YAN; LIU, ZONG-PING

    2015-01-01

    The steroid hormone 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2D3] plays an important role in maintaining a balance in calcium and bone metabolism. To study the effects of 1α,25-(OH)2D3 on osteoclast (OC) formation and bone resorption, OC differentiation was induced in bone marrow-derived mononuclear cells from Wistar rats with the addition of macrophage colony stimulating factor and receptor activator for nuclear factor-κB ligand in vitro. Cells were then treated with 1α,25-(OH)2D3 at 10−9, 10−8 or 10−7 mol/l. OCs were identified using tartrate-resistant acid phosphatase staining and activity was monitored in the absorption lacunae by scanning electron microscopy. Expression levels of functional proteins associated with bone absorption, namely carbonic anhydrase II, cathepsin K and matrix metalloproteinase-9 were evaluated by western blot analysis. The results showed that 1α,25-(OH)2D3 inhibited the formation and activation of OCs in a dose-dependent manner and downregulated the expression levels of bone absorption-associated proteins. PMID:26622436

  9. 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

  10. Titin and myosin, but not desmin, are linked during myofibrillogenesis in postmitotic mononucleated myoblasts.

    PubMed

    Hill, C S; Duran, S; Lin, Z X; Weber, K; Holtzer, H

    1986-12-01

    Monoclonal antibodies specific for the muscle protein titin have been used in conjunction with muscle-specific antibodies against myofibrillar myosin heavy chains (MHCs) and desmin to study myogenesis in cultured cells. Desmin synthesis is initiated in replicating presumptive myoblasts, whereas the synthesis of titin and MHC is initiated simultaneously in their progeny, the postmitotic, mononucleated myoblasts. Both titin and MHC are briefly localized to nonstriated and thereafter to definitively striated myofibrils. At no stage during myofibrillogenesis is either protein observed as part of a sequence of mini-sarcomeres. Titin antibodies bind to the A-I junction, MHC antibodies to the A bands in nascent, maturing, and mature myofibrils. In contrast, desmin remains distributed as longitudinal filaments until well after the definitive myofibrils have aligned laterally. This tight temporal and topographical linkage between titin and myosin is also observed in postmitotic, mononucleated myoblasts and multinucleated myotubes when myofibrillogenesis is perturbed with Colcemid or taxol. Colcemid induces elongating postmitotic mononucleated myoblasts and multinucleated myotubes to round up and form Colcemid myosacs. The myofibrils that emerge in these rounded cells are deployed in convoluted circles. The time required for their nonstriated myofibrils to transform into striated myofibrils is greatly protracted. Furthermore, as Colcemid induces immense desmin intermediate filament cables, the normal spatial relationships between emerging individual myofibrils is distorted. Despite these disturbances at all stages, the characteristic temporal and spatial relationship observed in normal myofibrils between titin and MHC is observed in myofibrils assembling in Colcemid-treated cells. Newly born postmitotic mononucleated myoblasts, or maturing myotubes, reared in taxol acquire a star-shaped configuration and are induced to assemble "pseudo-striated myofibrils." Pseudo

  11. 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

  12. Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice: dosage and the window of time

    PubMed Central

    Kovalenko, Olga A.; Azzam, Edouard I.; Ende, Norman

    2013-01-01

    The purpose of this study was to evaluate the window of time and dose of human umbilical-cord-blood (HUCB) mononucleated cells necessary for successful treatment of radiation injury in mice. Female A/J mice (27–30 weeks old) were exposed to an absorbed dose of 9–10 Gy of 137Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 108 or 2 × 108 HUCB mononucleated cells at 24–52 h after the irradiation. The antibiotic Levaquin was applied 4 h postirradiation. The increased dose of cord-blood cells resulted in enhanced survival. The enhancement of survival in animals that received 2 × 108 HUCB mononucleated cells relative to irradiated but untreated animals was highly significant (P < 0.01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24–52 h after exposure. PMID:23792493

  13. Analyses of basal media and serum for in vitro expansion of suspension peripheral blood mononucleated stem cell.

    PubMed

    Zainal Ariffin, Shahrul Hisham; Mohamed Rozali, Nur Akmal; Megat Abdul Wahab, Rohaya; Senafi, Sahidan; Zainol Abidin, Intan Zarina; Zainal Ariffin, Zaidah

    2016-08-01

    Transplantation of stem cells requires a huge amount of cells, deeming the expansion of the cells in vitro necessary. The aim of this study is to define the optimal combination of basal medium and serum for the expansion of suspension peripheral blood mononucleated stem cells (PBMNSCs) without resulting in loss in the differentiation potential. Mononucleated cells were isolated from both mice and human peripheral blood samples through gradient centrifugation and expanded in α-MEM, RPMI, MEM or DMEM supplemented with either NBCS or FBS. The suspension cells were then differentiated to osteoblast. Our data suggested that α-MEM supplemented with 10 % (v/v) NBCS gives the highest fold increase after 14 days of culture for both mice and human PBMNSCs, which were ~1.51 and ~2.01 times, respectively. The suspension PBMNSCs in the respective medium were also able to maintain osteoblast differentiation potential as supported by the significant increase in ALP specific activity. The cells are also viable during the differentiated states when using this media. All these data strongly suggested that α-MEM supplemented with 10 % NBCS is the best media for the expansion of both mouse and human suspension PBMNSCs. PMID:26231833

  14. 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

  15. 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

  16. [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

  17. 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. PMID:25624220

  18. Contaminant resorption during soil washing

    SciTech Connect

    Gombert, D.

    1993-10-01

    To evaluate the applicability of soil washing to a specific site requires some basic research in how contaminants are bound. Much can be learned from sequential extraction methodology based on micronutrient bioavailability studies wherein the soil matrix is chemically dissected to selectively remove particular fixation mechanisms independently. This procedure uses a series of progressively more aggressive solvents to dissolve the principle phases that make up a soil, however, the published studies do not appear to consider the potential for a contaminant released from one type of site to resorb on another site during an extraction. This physical model assumes no ion exchange or adsorption at sites either previously occupied by other ions, or exposed by the dissolution. Therefore, to make engineering use of the sequential extraction data, the release of contamination must be evaluated relative to the effects of resorption. Time release studies were conducted to determine the optimum duration for extraction to maximize complete destruction of the target matrix fraction while minimizing contaminant resorption. Tests with and without a potassium brine present to inhibit cesium resorption indicated extraction efficiency could be enhanced by as much as a factor of ten using the brine.

  19. Bacterial porins stimulate bone resorption.

    PubMed Central

    Meghji, S; Henderson, B; Nair, S P; Tufano, M A

    1997-01-01

    Porins are abundant outer membrane proteins of gram-negative bacteria involved in transport of low-molecular-mass molecules. During the past decade, porins from a number of bacteria have also been shown to have proinflammatory activities including inducing the synthesis of proinflammatory mediators (cytokines, platelet-activating factor, and nitric oxide) in cultured cells and inducing inflammation in vivo. With this range of actions, it was possible that porins could also interact with bone cells to cause aberrant bone remodeling and that this could contribute to the bone destruction seen in gram-negative bone infections. By using purified preparations of Salmonella typhimurium and Pseudomonas aeruginosa porins, in the presence of polymyxin B, it was possible to induce concentration-dependent loss of calcium from cultured murine calvaria at porin concentrations in the range of 1 to 10 nM. The mechanism of action of the porins was determined by the inclusion of inhibitors of cyclooxygenase or inflammatory cytokines in the culture media. The bone-resorbing activity of both porins was not inhibited by the cyclooxygenase inhibitor indomethacin or by neutralizing the activity of tumor necrosis factor. Indeed, relatively high concentrations of these agents produced an unexpected increase in the bone resorption induced by the porins. In contrast, porin-induced bone resorption could be inhibited by relatively high concentrations of the natural inhibitor of interleukin-1 (IL-1 receptor antagonist). It appears that these porins stimulate bone resorption by a mechanism distinct from that of lipopolysaccharide, and the possibility therefore exists that porins play a role in bone destruction in gram-negative bacterial infections of bone. PMID:9119467

  20. Microcracks and osteoclast resorption activity in vitro.

    PubMed

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

    2012-03-01

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

  1. 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.

  2. Variation in nutrient resorption by desert shrubs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant nutrient resorption prior to leaf senescence is an important nutrient conservation mechanism for aridland plant species. However, little is known regarding the phylogenetic and environmental factors influencing this trait. Our objective was to compare nitrogen and phosphorus resorption in a ...

  3. 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

  4. In vitro expression of hard metal dust (WC-Co)--responsive genes in human peripheral blood mononucleated cells.

    PubMed

    Lombaert, Noömi; Lison, Dominique; Van Hummelen, Paul; Kirsch-Volders, Micheline

    2008-03-01

    Hard metals consist of tungsten carbide (WC) and metallic cobalt (Co) particles and are important industrial materials produced for their extreme hardness and high wear resistance properties. While occupational exposure to metallic Co alone is apparently not associated with an increased risk of cancer, the WC-Co particle mixture was shown to be carcinogenic in exposed workers. The in vitro mutagenic/apoptogenic potential of WC-Co in human peripheral blood mononucleated cells was previously demonstrated by us. This study aimed at obtaining a broader view of the pathways responsible for WC-Co induced carcinogenicity, and in particular genotoxicity and apoptosis. We analyzed the profile of gene expression induced in vitro by WC-Co versus control (24 h treatment) in human PBMC and monocytes using microarrays. The most significantly up-regulated pathways for WC-Co treated PBMC were apoptosis and stress/defense response; the most down-regulated was immune response. For WC-Co treated monocytes the most significantly up- and down-regulated pathways were nucleosome/chromatin assembly and immune response respectively. Quantitative RT-PCR data for a selection of the most strongly modulated genes (HMOX1, HSPA1A, HSPA1L, BNIP3, BNIP3L, ADORA2B, MT3, PLA2G7, TNFAIP6), and some additionally chosen apoptosis related genes (BCL2, BAX, FAS, FASL, TNFalpha), confirmed the microarray data after WC-Co exposure and demonstrated limited differences between the Co-containing compounds. Overall, this study provides the first analysis of gene expression induced by the WC-Co mixture showing a large profile of gene modulation and giving a preliminary indication for a hypoxia mimicking environment induced by WC-Co exposure. PMID:18078969

  5. In vitro expression of hard metal dust (WC-Co) - responsive genes in human peripheral blood mononucleated cells

    SciTech Connect

    Lombaert, Nooemi Lison, Dominique; Van Hummelen, Paul; Kirsch-Volders, Micheline

    2008-03-01

    Hard metals consist of tungsten carbide (WC) and metallic cobalt (Co) particles and are important industrial materials produced for their extreme hardness and high wear resistance properties. While occupational exposure to metallic Co alone is apparently not associated with an increased risk of cancer, the WC-Co particle mixture was shown to be carcinogenic in exposed workers. The in vitro mutagenic/apoptogenic potential of WC-Co in human peripheral blood mononucleated cells was previously demonstrated by us. This study aimed at obtaining a broader view of the pathways responsible for WC-Co induced carcinogenicity, and in particular genotoxicity and apoptosis. We analyzed the profile of gene expression induced in vitro by WC-Co versus control (24 h treatment) in human PBMC and monocytes using microarrays. The most significantly up-regulated pathways for WC-Co treated PBMC were apoptosis and stress/defense response; the most down-regulated was immune response. For WC-Co treated monocytes the most significantly up- and down-regulated pathways were nucleosome/chromatin assembly and immune response respectively. Quantitative RT-PCR data for a selection of the most strongly modulated genes (HMOX1, HSPA1A, HSPA1L, BNIP3, BNIP3L, ADORA2B, MT3, PLA2G7, TNFAIP6), and some additionally chosen apoptosis related genes (BCL2, BAX, FAS, FASL, TNF{alpha}), confirmed the microarray data after WC-Co exposure and demonstrated limited differences between the Co-containing compounds. Overall, this study provides the first analysis of gene expression induced by the WC-Co mixture showing a large profile of gene modulation and giving a preliminary indication for a hypoxia mimicking environment induced by WC-Co exposure.

  6. [Multiple tooth resorption in an Italian greyhound].

    PubMed

    Roux, P; Stich, H; Schawalder, P

    2011-06-01

    An Italian greyhound was presented three times during a two-year period for dental prophylaxis due to periodontal disease. Clinical examination revealed lesions on several teeth. Radiographs revealed extensive resorptive root lesions. On histological examination, the presence of odontoclasts and signs of boney remodeling of the roots confirmed the resorptive nature of the lesions. Given the extent of the lesions, and poor prognosis with conservative treatment alone, teeth affected by the most severe resorption were extracted at each visit using a flap technique combined with alveolar vestibular osteotomy. Dental resorptive lesions are rarely detected in the dog but may be more frequent than previously thought. The routine use of dental radiographs can be used to reveal these lesions in the dog. PMID:21638265

  7. 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

  8. 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

  9. Circadian Clock Regulates Bone Resorption in Mice.

    PubMed

    Xu, Cheng; Ochi, Hiroki; Fukuda, Toru; Sato, Shingo; Sunamura, Satoko; Takarada, Takeshi; Hinoi, Eiichi; Okawa, Atsushi; Takeda, Shu

    2016-07-01

    The circadian clock controls many behavioral and physiological processes beyond daily rhythms. Circadian dysfunction increases the risk of cancer, obesity, and cardiovascular and metabolic diseases. Although clinical studies have shown that bone resorption is controlled by circadian rhythm, as indicated by diurnal variations in bone resorption, the molecular mechanism of circadian clock-dependent bone resorption remains unknown. To clarify the role of circadian rhythm in bone resorption, aryl hydrocarbon receptor nuclear translocator-like (Bmal1), a prototype circadian gene, was knocked out specifically in osteoclasts. Osteoclast-specific Bmal1-knockout mice showed a high bone mass phenotype due to reduced osteoclast differentiation. A cell-based assay revealed that BMAL1 upregulated nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (Nfatc1) transcription through its binding to an E-box element located on the Nfatc1 promoter in cooperation with circadian locomotor output cycles kaput (CLOCK), a heterodimer partner of BMAL1. Moreover, steroid receptor coactivator (SRC) family members were shown to interact with and upregulate BMAL1:CLOCK transcriptional activity. Collectively, these data suggest that bone resorption is controlled by osteoclastic BMAL1 through interactions with the SRC family and binding to the Nfatc1 promoter. © 2016 American Society for Bone and Mineral Research. PMID:26841172

  10. N-acetyl muramyl dipeptide stimulation of bone resorption in tissue culture.

    PubMed Central

    Dewhirst, F E

    1982-01-01

    N-Acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), a structurally defined fragment of bacterial peptidoglycan, stimulated significant release of previously incorporated 45Ca from fetal rat bones in tissue culture over the concentration range of 0.1 to 10.0 micrograms/ml. MDP-Stimulated bone resorption was not inhibited by the addition of the prostaglandin synthetase inhibitor indomethacin to the culture medium. MDP was neither mitogenic for nor stimulated the release of osteoclast-activating factor from cultured human peripheral blood mononuclear cells. Thus, MDP-stimulated bone resorption in vitro is mediated by a mechanism which is not dependent upon prostaglandins or osteoclast-activating factor. 6-O-Stearoyl-N-acetyl-muramyl-L-alanyl-D-isoglutamine, a lipophilic analog of MDP, was slightly more potent than MDP. Two diastereomers of MDP, N-acetyl-muramyl-L-alanyl-L-isoglutamine and N-acetyl-muramyl-D-alanyl-D-isoglutamine, which are inactive as adjuvants, were at least 1,000 times less active than MDP in stimulating bone resorption. The stereochemical specificity for bone-resorptive activity paralleled that required for adjuvant activity, macrophage activation, and activation of the reticuloendothelial system. PMID:7054120

  11. Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

    PubMed

    Takano, H; Takahashi, T; Nakata, A; Nogami, S; Yusa, K; Kuwajima, S; Yamazaki, M; Fukuda, M

    2016-05-01

    The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing. PMID:26946239

  12. Tfe3 expression is closely associated to macrophage terminal differentiation of human hematopoietic myeloid precursors

    SciTech Connect

    Zanocco-Marani, Tommaso; Vignudelli, Tatiana; Gemelli, Claudia; Pirondi, Sara; Testa, Anna; Montanari, Monica; Parenti, Sandra; Tenedini, Elena; Grande, Alexis; Ferrari, Sergio . E-mail: sergio@unimo.it

    2006-12-10

    The MItf-Tfe family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors encodes four family members: MItf, Tfe3, TfeB and TfeC. In vitro, each protein of the family binds DNA in a homo- or heterodimeric form with other family members. Tfe3 is involved in chromosomal translocations recurrent in different tumors and it has been demonstrated, by in vivo studies, that it plays, redundantly with MItf, an important role in the process of osteoclast formation, in particular during the transition from mono-nucleated to multi-nucleated osteoclasts. Since mono-nucleated osteoclasts derive from macrophages we investigated whether Tfe3 might play a role upstream during hematopoietic differentiation. Here we show that Tfe3 is able to induce mono-macrophagic differentiation of U937 cells, in association with a decrease of cell proliferation and an increase of apoptosis. We also show that Tfe3 does not act physiologically during commitment of CD34+ hematopoietic stem cells (HSCs), since it is not able to direct HSCs toward a specific lineage as observed by clonogenic assay, but is a strong actor of terminal differentiation since it allows human primary myeloblasts' maturation toward the macrophage lineage.

  13. Unusual external resorption of a maxillary lateral.

    PubMed

    Giunta, J L; Kaplan, M A

    1994-01-01

    This article defines an unusual previously unreported entity afflicting a maxillary lateral incisor. Labial idiopathic external root resorption just apical to the cemento-enamel presented as a gingival (periodontal) problem and was misinterpreted as cervical dental caries. This report defines a new possibility for a radicular defect in a maxillary lateral incisor that may cause periodontal problems. PMID:8054293

  14. 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)

  15. 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

  16. 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

  17. [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

  18. TDAG8 activation inhibits osteoclastic bone resorption.

    PubMed

    Hikiji, Hisako; Endo, Daisuke; Horie, Kyoji; Harayama, Takeshi; Akahoshi, Noriyuki; Igarashi, Hidemitsu; Kihara, Yasuyuki; Yanagida, Keisuke; Takeda, Junji; Koji, Takehiko; Shimizu, Takao; Ishii, Satoshi

    2014-02-01

    Although the roles of acids in bone metabolism are well characterized, the function of proton-sensing receptors in bone metabolism remains to be explored. In this study, we evaluated the role of proton-sensing receptor T-cell death-associated gene 8 (TDAG8) in osteoclastic activity during bone loss after ovariectomy. Through observations of bone mineral content, we found that pathological bone resorption was significantly exacerbated in mice homozygous for a gene trap mutation in the Tdag8 gene. Furthermore, osteoclasts from the homozygous mutant mice resorbed calcium in vitro more than the osteoclasts from the heterozygous mice did. Impaired osteoclast formation under acidic conditions was ameliorated in cultures of bone marrow cells by Tdag8 gene mutation. Extracellular acidification changed the cell morphology of osteoclasts via the TDAG8-Rho signaling pathway. These results suggest that the enhancement of TDAG8 function represents a new strategy for preventing bone resorption diseases, such as osteoporosis. PMID:24221084

  19. 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.

  20. 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. PMID:9680910

  1. Molecular and cellular basis of bone resorption.

    PubMed

    Gruber, Reinhard

    2015-02-01

    Osteoclast research has an exciting history and a challenging future. More than 3 decades ago, it became evident that bone-resorbing osteoclasts are of hematopoietic origin and are ultimately linked to the "basic multicellular unit," where they team up with the other cell types, including bone-forming osteoblasts. Since 2 decades, we have learned about the signaling pathways controlling genes relevant for osteoclastogenesis and bone resorption. It took another decade until the hypothesized "osteoclast differentiation" factor was discovered and was translated into an approved pharmacologic strategy. Here, the focus is on another molecular target, cathepsin K, a cysteine protease being released by the osteoclast into the resorption compartment. Genetic deletion and pharmacological blocking of cathepsin K reduces bone resorption but with ongoing bone formation. This observation not only holds great promise to become a new pharmacologic strategy, but it also provides new insights into the coordinated work of cells in the "basic multicellular unit" and thus, bridges the history and future of osteoclast research. This article is a short primer on osteoclast biology for readers of the special issue on odanacatib, a cathepsin K inhibitor. PMID:25223736

  2. TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption

    PubMed Central

    Witwicka, Hanna; Jia, Hong; Kutikov, Artem; Reyes-Gutierrez, Pablo; Li, Xiangdong; Odgren, Paul R.

    2015-01-01

    Plekhm1 is a large, multi-modular, adapter protein implicated in osteoclast vesicle trafficking and bone resorption. In patients, inactivating mutations cause osteopetrosis, and gain-of-function mutations cause osteopenia. Investigations of potential Plekhm1 interaction partners by mass spectrometry identified TRAFD1 (FLN29), a protein previously shown to suppress toll-like receptor signaling in monocytes/macrophages, thereby dampening inflammatory responses to innate immunity. We mapped the binding domains to the TRAFD1 zinc finger (aa 37-60), and to the region of Plekhm1 between its second pleckstrin homology domain and its C1 domain (aa 784-986). RANKL slightly increased TRAFD1 levels, particularly in primary osteoclasts, and the co-localization of TRAFD1 with Plekhm1 also increased with RANKL treatment. Stable knockdown of TRAFD1 in RAW 264.7 cells inhibited resorption activity proportionally to the degree of knockdown, and inhibited acidification. The lack of acidification occurred despite the presence of osteoclast acidification factors including carbonic anhydrase II, a3-V-ATPase, and the ClC7 chloride channel. Secretion of TRAP and cathepsin K were also markedly inhibited in knockdown cells. Truncated Plekhm1 in ia/ia osteopetrotic rat cells prevented vesicle localization of Plekhm1 and TRAFD1. We conclude that TRAFD1, in association with Plekhm1/Rab7-positive late endosomes-early lysosomes, has a previously unknown role in vesicle trafficking, acidification, and resorption in osteoclasts. PMID:25992615

  3. Lectin-mediated effects on bone resorption in vitro: a morphological and functional study

    SciTech Connect

    Popoff, S.N.

    1986-01-01

    Lectins have been used to study the structure and function of a variety of cells and tissues. The authors used 4 different lectins, concanavalin A (con A), wheat germ agglutinin (WGA), soybean agglutinin (SBA) and peanut agglutinin (PNA) as in vitro biological probes to study the osteoclast, a multinucleated bone cell that is widely accepted as the primary effector cell responsible for normal bone resorption. They evaluated the effects of each of these lectins on osteoclastic bone resorbing activity and then examined mechanisms that may be responsible for the activation and/or inhibition of osteoclastic activity. Using con A and hemocyanin, a marker molecule used to visualize cell-bound con A via scanning electron microscopy, they demonstrated that osteoclasts have specific con A binding sites on their cell surface. They conducted a series of /sup 45/Ca bone release assays demonstrating that con A has a dose-dependent biphasic effect on bone resorption; stimulation at low concentrations and inhibition at higher concentrations. The findings suggest that the specificity of lectin binding to cell surface receptors may play an important role in the induction of altered cell function. Recently, cells of the mononuclear phagocyte system have been proposed as surrogates of less readily available osteoclasts. They used a macrophage-devitalized bone culture system to evaluate the effects of con A and SBA on the attachment of macrophages to bone and their subsequent functional activity. The results showed that con A, but not SBA, alters the morphology and function of macrophages on a devitalized bone surface. The results support the hypothesis that certain, specific saccharides regulate the interaction between macrophages and bone.

  4. IL-37 inhibits lipopolysaccharide-induced osteoclast formation and bone resorption in vivo.

    PubMed

    Saeed, Jafari; Kitaura, Hideki; Kimura, Keisuke; Ishida, Masahiko; Sugisawa, Haruki; Ochi, Yumiko; Kishikawa, Akiko; Takano-Yamamoto, Teruko

    2016-07-01

    IL-37 is a newly defined member of the IL-1 cytokine family. It has been reported that IL-37 inhibited innate immunity and inflammatory responses in autoimmune diseases and tumors. IL-37 also inhibited Lipopolysaccharide (LPS)-induced immunological reaction. LPS is a bacterial cell wall component that is capable of inducing osteoclast formation and pathological bone resorption. However, there is no study to investigate the effect of IL-37 on LPS-induced osteoclast formation and bone resorption. The purpose of this study is to investigate the effect of IL-37 in LPS-induced osteoclast formation and bone resorption. LPS was administrated with or without IL-37 by subcutaneous injection on mice calvariae. The number of osteoclasts, the level of tartrate-resistant acid phosphatase (TRAP) and cathepsin K mRNA, the ratio of the bone resorption pits and the level of C-terminal telopeptide fragments of type I collagen cross-Links as a marker of bone resorption in mice administrated both LPS and IL-37 were lower than that in mice administrated LPS alone. Real-time RT-PCR was performed to analyze osteoclast related cytokines RANKL, TNF-α and IL-1β mRNA levels in vivo. RANKL, TNF-α and IL-1β mRNAs were increased in the LPS alone administrated mice as compared with PBS administrated groups. On the other hand, RANKL, TNF-α and IL-1β mRNAs were inhibited in the IL-37 and LPS administrated mice as compared with LPS alone administrated group. In vitro analysis, there was no effect of IL-37 in RANKL-induced osteoclast formation, TNF-α-induced osteoclast formation and cell viability from bone marrow macrophages as osteoclast precursor and LPS-induced RANKL expression from stromal cells. These results indicated that IL-37 inhibited LPS-induced osteoclast formation and bone resorption via inhibition of LPS-induced osteoclast related cytokines, but might not directly inhibit osteoclast formation on osteoclast precursor and RANKL expression on stromal cells. PMID:27154248

  5. 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

  6. 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

  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. 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

  9. The effects of icariine concentration on osteoclasts bone resorption induced by titanium particles in vitro.

    PubMed

    Zhang, Yiyuan; Lin, Yu; Xiao, Lili; Feng, Eryou; Wang, Wulian; Lin, Liqiong

    2015-09-01

    In artificial joint replacement, osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening. To extend the life of the prosthesis, detailed mechanisms of aseptic loosening and the ways to prevent it should be explored. The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles. Macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL) were used to generate osteoclasts from RAW264.7 precursors. The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay. The cells were treated with titanium particles, titanium particles with icariine and culture medium only (control), respectively. At 48 h after treatment, the expression level of receptor activator of NF-kB (RANK) was detected by ELISA, and messenger RNA (mRNA) levels of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase 9 (MMP-9), carbonic anhydrase II (CAII) and Cathepsin K (CtsK) were determined by real-time polymerase chain reaction. Western blot was applied to analyze the expression levels of TRAP, RANK and CtsK. In addition, bone chips were cultured in the above conditions, and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips. After treatment with icariine, expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium, mRNA and protein levels of TRAP, CAII, MMP-9 and CtsK were reduced as well. In addition, the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging. Icariine could inhibit bone resorption of osteoclast induced by titanium particle, and it might be used as a promising drug for treating of aseptic loosening. PMID:26816641

  10. 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

  11. Spontaneous Resorption of a Penetrating Orbital Bone Fracture Fragment.

    PubMed

    Campbell, Ashley A; Cunnane, Mary Elizabeth; Dunn, Gavin P; Gray, Stacy Tutt; Lefebvre, Daniel R

    2015-01-01

    The authors describe a 20-year-old man who sustained multiple facial fractures in a high-speed motor vehicle crash, including a bone fragment from a skull base fracture that penetrated the orbital soft tissues superomedially. Serial CT scans documented spontaneous resorption over a 6-month period. While it is known that autologous bone grafts used in craniofacial reconstruction exhibit variable amounts of bone resorption, the complete resorption of an intraorbital fracture fragment has not been documented in the literature. His clinical care and the report of his case were undertaken in a fashion in accordance with the principles of the Health Insurance Portability and Accountability Act regulations. PMID:24833452

  12. 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

  13. Solanum malacoxylon toxicity: inhibition of bone resorption.

    PubMed

    Santos, M N; Nunes, V A; Nunes, I J; Barros, S S; Wasserman, R H; Krook, L

    1976-10-01

    Young rabbits on high (0.57%) or low (0.24%) calcium were given an aqueous extract of Solanum malacoxylon (S.m.) leaves (20 g dried leaves/200 ml distilled water) intragastrically at 0, 12 and 36 hours. On bothe diets S.m. induced progressive hypophosphatasemia but serum calcium and phosphorus underwent only minor changes. In rabbits necropsied at 0, 12, 36, 60, 84 and 108 hours, S.m. was shown to have a negative effect on the resorbing osteocytes. With retarded osteocytic osteolysis, osteopetrosis resulted. Further regressive changes in the osteocytes resulted in osteonecrosis which was observed within 12 hours after administration of S.m. extract. The osteonecrosis, combined with retarded apposition, later resulted in osteopenia. It was concluded that the recommended dietary calcium for growing rabbits--about 0.6%--is too high. Whereas the histologic appearance of bone in rabbits fed low calcium was normal, bones from rabbits on high calcium showed retarded resorption and the rabbits had a relative hypophosphatasemia. PMID:185004

  14. 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

  15. 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

  16. 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

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

    PubMed Central

    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 osteoclastspecific 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. PMID:26108893

  18. Natural products for treatment of bone erosive diseases: The effects and mechanisms on inhibiting osteoclastogenesis and bone resorption.

    PubMed

    An, Jing; Hao, Dingjun; Zhang, Qian; Chen, Bo; Zhang, Rui; Wang, Yi; Yang, Hao

    2016-07-01

    Excessive bone resorption plays a central role on the development of bone erosive diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Regulation of osteoclast differentiation is considered an effective therapeutic target to the treatment of pathological bone loss. Natural plant-derived products, with potential therapeutic and preventive activities against bone-lytic diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities, which are more suitable for long-term use than chemically synthesized medicines. In this review, we summarized the detailed research progress on the active compounds derived from medical plants with potential anti-resorptive effects and their molecular mechanisms on inhibiting osteoclast formation and function. The active ingredients derived from natural plants that are efficacious in suppressing osteoclastogenesis and bone resorption include flavonoids, terpenoids (sesquiterpenoids, diterpenoids, triterpenoids), glycosides, lignans, coumarins, alkaloids, polyphenols, limonoids, quinones and others (steroid, oxoxishhone, fatty acid). Studies have shown that above natural products exert the inhibitory effects via regulating many factors involved in the process of osteoclast differentiation and bone resorption, including the essential cytokines (RANKL, M-CSF), transcription factors (NFATc1, c-Fos), signaling pathways (NF-κB, MAPKs, Src/PI3K/Akt, the calcium ion signaling), osteoclast-specific genes (TRAP, CTSK, MMP-9, integrin β3, OSCAR, DC-STAMP, Atp6v0d2) and local factors (ROS, LPS, NO). The development of osteoclast-targeting natural products is of great value for the prevention or treatment of bone diseases and for bone regenerative medicine. PMID:27131574

  19. Healing of the root surface-associated periodontium: an immunohistochemical study of orthodontic root resorption in man.

    PubMed

    Sismanidou, C; Hilliges, M; Lindskog, S

    1996-10-01

    The purpose of the present investigation was to study resorption and regeneration of periodontal tissues incident to orthodontic tooth movement, in particular cells resorbing the root surface and the subsequent regeneration of the periodontal epithelial network and forming reparative cementum. The study was carried out using a select number of immunohistochemical markers on extracted human teeth which had been treated orthodontically. The most striking finding in the resorbing areas was the presence of what appeared to be two populations of KP 1+ mononuclear cells located at a distance of 50-100 microns from the root surface and multinucleated cells in resorption lacunae in close contact with the root surface. KP 1+ has previously not been reported for odontoclasts. The mononuclear KP 1+ cells in the periodontal ligament may represent either precursors to odontoclasts or phagocytic scavenger cells of the macrophage lineage. The subsequent healing of the resorption lacunae was characterized by re-establishment of nervous, vascular and epithelial tissues as evidenced by S-100+ filamentous delicate structures, factor VIII+ vessels and cytokeratin+ clusters of cells, respectively. However, cytokeratin+ single cells in close contact with the unresorbed cementum did not re-appear within the healing period. Although the present results are not quantitative in nature, cementoblasts located in the vicinity of resorption lacunae, especially healing ones, appeared to show an up-regulation of epidermal growth factor (EGF) receptors. It may be suggested the intense positive staining for EGF receptors may be an expression of an auto- or paracrine stimulatory pathway increasing the rate of reparative cementum formation. PMID:8942091

  20. Tumour macrophages as potential targets of bisphosphonates

    PubMed Central

    2011-01-01

    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to

  1. 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

  2. Tooth root resorption induced in rats by diphenylhydantoin and parathyroidectomy.

    PubMed Central

    Robinson, P. B.; Harvey, W.

    1989-01-01

    Changes in bone, cartilage and the dentition in animals and man following the administration of anticonvulsant drugs resemble those seen in hypoparathyroidism and pseudohypoparathyroidism. Groups of 21-day-old rats were treated with diphenylhydantoin, parathyroidectomized, or made hypocalcaemic with a calcium-deficient diet. Histological examination revealed extensive resorption of cementum and dentine in the molars of the drug-treated and parathyroidectomized rats, but not in the hypocalcaemic or control groups. Localization of injected tetracycline by fluorescence showed that the resorption affected the distal side of the tooth roots and had occurred after root formation. No changes in cementum formation on the mesial side of the roots had occurred in any of the experimental groups. These results suggest that diphenylhydantoin induces a condition similar to pseudohypoparathyroidism in which the resistance of tooth roots to resorption is reduced. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:2923790

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

    PubMed

    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

  4. 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

  5. Peculiarities of the bone tissue resorption under microgravity conditions

    NASA Astrophysics Data System (ADS)

    Rodionova, N.; Oganov, V.; Polkovenko, O.; Nitsevich, T.

    The actual problem - peculiarities of resorptive processes in the spongiose of thingbones - we studied with the use of tranmissive electron microscopy in experiments on rats (American space station SLS-2) and on monkeys Macaca mulatt? (BION-11). Animals were onboard during 2 weeks. There was established, that the resorption happen with osteoclasts participation. They can create groups of cells. In the osteoclasts population we indicated not typical for the control (ground experiment) "giant" cells, which have on ultrathin sections 5-6 nuclei, many lysosomes, well developed "light" zone and "brush-border". The destruction of minera lized matrix in bone lacunas also happens by the way of osteolytic activity of osteocytes. Lysosome ferments of osteocytes are secreted by the eczocytosis. The osteocytic osteolysis, as well as the osteoclastic one can be seen as a physiological, gormon-dependent mechanism of resorption. The presence of a considerable number of neutrophiles, which enter in some zones of resorption is also typical. When these neutrophiles destruct, they release lysosomic ferments that dissolve the bone matrix. In some zones of resorption we noted the presence of the row from collagen fibrils, which loosed crystals , on mineralized matrix borders. The cell detritus is noted in zones of surface dissolving among crystallic conglomerates. It certificates the processes of osteogenic cells destruction that happen here. So, under the microgravity conditions in zones of adaptive remodeling of the spongiose the processes of the bone tissue resorption happen by some ways, namely: by the functional activization of osteoclasts; by the osteocytic osteolysis increasing; as a result of hydrolytic activity of neutrophiles, entering in these zones, and also by the local demineralization and further destruction of bone matrix surface zones.

  6. Management of invasive cervical resorption in a maxillary central incisor

    PubMed Central

    Kumar, S. Senthil; Kumar, N. S. Mohan; Karunakaran, J. V.; Nagendran, S.

    2015-01-01

    Invasive cervical resorption is often not diagnosed properly, leading to improper treatment or unnecessary loss of the tooth structure. Early diagnosis and appropriate treatment are the keys to a successful outcome of therapy. Invasive cervical resorption is often seen in the cervical area of the tooth, but because it is initiated apical to the epithelial attachment, it can present anywhere in the root. In the early stages, it may be symmetrical, but larger lesions have the tendency to be asymmetrical. It can expand apically or coronally. PMID:26538950

  7. 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

  8. 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. PMID:26124217

  9. 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

  10. [A case of appendicular supplementary root with external root resorption].

    PubMed

    González Bahillo, J; Martínez Insua, A; Varela Patiño, P; Rivas Lombardero, P; Paz Pumpido, F

    1991-01-01

    The case of a lateral maxillary incisor with a supplementary root fractured by external root resorption, is presented. The role played for the periodontal disease is shown in the clinical and radiographic achievements, and their implications in the pulpal disease. Endodontic therapy was performed and the diagnosis confirmed in the specimen histological research. PMID:1858059

  11. Azanitrile Cathepsin K Inhibitors: Effects on Cell Toxicity, Osteoblast-Induced Mineralization and Osteoclast-Mediated Bone Resorption

    PubMed Central

    Ren, Zhong-Yuan; Machuca-Gayet, Irma; Domenget, Chantal; Buchet, Rene; Wu, Yuqing; Jurdic, Pierre; Mebarek, Saida

    2015-01-01

    Aim The cysteine protease cathepsin K (CatK), abundantly expressed in osteoclasts, is responsible for the degradation of bone matrix proteins, including collagen type 1. Thus, CatK is an attractive target for new anti-resorptive osteoporosis therapies, but the wider effects of CatK inhibitors on bone cells also need to be evaluated to assess their effects on bone. Therefore, we selected, among a series of synthetized isothiosemicarbazides, two molecules which are highly selective CatK inhibitors (CKIs) to test their effects on osteoblasts and osteoclasts. Research Design and Methods Cell viability upon treatment of CKIs were was assayed on human osteoblast-like Saos-2, mouse monocyte cell line RAW 264.7 and mature mouse osteoclasts differentiated from bone marrow. Osteoblast-induced mineralization in Saos-2 cells and in mouse primary osteoblasts from calvaria, with or without CKIs,; were was monitored by Alizarin Red staining and alkaline phosphatase activity, while osteoclast-induced bone resorption was performed on bovine slices. Results Treatments with two CKIs, CKI-8 and CKI-13 in human osteoblast-like Saos-2, murine RAW 264.7 macrophages stimulated with RANKL and mouse osteoclasts differentiated from bone marrow stimulated with RANKL and MCSF were found not to be toxic at doses of up to 100 nM. As probed by Alizarin Red staining, CKI-8 did not inhibit osteoblast-induced mineralization in mouse primary osteoblasts as well as in osteoblast-like Saos-2 cells. However, CKI-13 led to a reduction in mineralization of around 40% at 10–100 nM concentrations in osteoblast-like Saos-2 cells while it did not in primary cells. After a 48-hour incubation, both CKI-8 and CKI-13 decreased bone resorption on bovine bone slices. CKI-13 was more efficient than the commercial inhibitor E-64 in inhibiting bone resorption induced by osteoclasts on bovine bone slices. Both CKI-8 and CKI-13 created smaller bone resorption pits on bovine bone slices, suggesting that the mobility of

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

    PubMed

    Hattersley, G; Chambers, T J

    1989-09-01

    throughout the incubation period. This suggests that mononuclear cells with characteristics of osteoclasts exist that are able to excavate bone. CT receptor-positive cells slightly preceded the development of bone-resorptive function, implying that CT receptors develop before the acquisition of bone-resorptive capacity by osteoclasts. Peritoneal macrophages, blood mononuclear cells, and cells of the J774 macrophage cell line failed to either resorb bone or express CT receptors, even after incubation with 1,25-(OH)2D3 for 14 days. These results show a strong and specific correlation between the generation of bone-resorptive cells and CT receptor-positive cells, and suggest that CT receptor express PMID:2547591

  13. 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. PMID:25814244

  14. 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

  15. 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

  16. 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

  17. 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

  18. Pharmacological diversity among drugs that inhibit bone resorption.

    PubMed

    Russell, R Graham G

    2015-06-01

    Drugs that inhibit bone resorption ('anti-resorptives') continue to dominate the therapy of bone diseases characterized by enhanced bone destruction, including Paget's disease, osteoporosis and cancers. The historic use of oestrogens for osteoporosis led on to SERMs (Selective Estrogen Receptor Modulators, e.g. raloxifene and bazedoxifene). Currently the mainstay of treatment worldwide is still with bisphosphonates, as used clinically for over 40 years. The more recently introduced anti-RANK-ligand antibody, denosumab, is also very effective in reducing vertebral, non-vertebral and hip fractures. Odanacatib is the only cathepsin K inhibitor likely to be registered for clinical use. The pharmacological basis for the action of each of these drug classes is different, enabling choices to be made to ensure their optimal use in clinical practice. PMID:26048735

  19. Modulation of osteoclast differentiation and bone resorption by Rho GTPases

    PubMed Central

    Touaitahuata, Heiani; Blangy, Anne; Vives, Virginie

    2014-01-01

    Bone is a dynamic tissue constantly renewed through a regulated balance between bone formation and resorption. Excessive bone degradation by osteoclasts leads to pathological decreased bone density characteristic of osteolytic diseases such as post-menopausal osteoporosis or bone metastasis. Osteoclasts are multinucleated cells derived from hematopoietic stem cells via a complex differentiation process. Their unique ability to resorb bone is dependent on the formation of the actin-rich sealing zone. Within this adhesion structure, the plasma membrane differentiates into the ruffled border where protons and proteases are secreted to demineralize and degrade bone, respectively. On the bone surface, mature osteoclasts alternate between stationary resorptive and migratory phases. These are associated with profound actin cytoskeleton reorganization, until osteoclasts die of apoptosis. In this review, we highlight the role of Rho GTPases in all the steps of osteoclasts differentiation, function, and death and conclude on their interest as targets for treatment of osteolytic pathologies. PMID:24614674

  20. Spontaneous resorption of sub-retinal cortical lens material

    PubMed Central

    Gadkari, Salil S; Kulkarni, Sucheta R; Dole, Kuldeep

    2014-01-01

    We report a rare case of retained sub-retinal cortical material, which underwent spontaneous resorption. Patient presented with a left eye traumatic retinal detachment with a large retinal tear and posteriorly dislocated cataractous lens. Vitrectomy, lensectomy, silicone oil injection, and endolaser were performed. A good visual result was achieved. The report draws attention to this condition and highlights possible technique for minimizing risk of this complication in similar cases. PMID:25116782

  1. 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

  2. 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

  3. Tropomyosin 4 regulates adhesion structures and resorptive capacity in osteoclasts.

    PubMed

    McMichael, Brooke K; Lee, Beth S

    2008-02-01

    Tropomyosins (Tms) are alpha-helical dimers that bind and stabilize actin microfilaments while regulating their accessibility to other actin-associated proteins. Four genes encode expression of over forty Tms, most of which are expressed in nonmuscle cells. In recent years, it has become clear that individual Tm isoforms may regulate specific actin pools within cells. In this study, we examined how osteoclast function may be regulated by the tropomyosin isoform Tm-4, which we previously showed to be highly localized to podosomes and sealing zones of osteoclasts. RNAi-mediated knockdown of Tm-4, both in RAW264.7- and mouse marrow-derived osteoclasts, resulted in thinning of the actin ring of the sealing zone. Knockdown of Tm-4 also resulted in diminished bone resorptive capacity and altered resorption pit shape. In contrast, osteoclasts overexpressing Tm-4 demonstrated thickened podosomes on glass as well as thickened, aberrant actin structures on bone, and diminished motility and resorptive capacity. These results indicate that Tm-4 plays a role in regulating adhesion structures of osteoclasts, most likely by stabilizing the actin microfilaments present in podosomes and the sealing zone. PMID:18036591

  4. 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

  5. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype. PMID:25319333

  6. 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.

  7. 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. PMID:26740180

  8. 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

  9. Rhinacanthin C Inhibits Osteoclast Differentiation and Bone Resorption: Roles of TRAF6/TAK1/MAPKs/NF-κB/NFATc1 Signaling

    PubMed Central

    Tomomura, Mineko; Suzuki, Ryuichiro; Shirataki, Yoshiaki; Sakagami, Hiroshi; Tamura, Nobuaki; Tomomura, Akito

    2015-01-01

    Rhinacanthin C is a naphthoquinone ester with anti-inflammatory activity, found in Rhinacanthus nasutus (L) Kurz (Acanthaceae). We found that rhinacanthin C inhibited osteoclast differentiation stimulated by the receptor activator of nuclear factor-κB ligand (RANKL) in mouse bone marrow macrophage cultures, although the precise molecular mechanisms underlying this phenomenon are unclear. In this study, we investigated the inhibitory mechanisms of rhinacanthin C in osteoclastogenesis. Rhinacanthin C suppressed RANKL-induced nuclear factor of activated T cells c1 (NFATc1) expression. Phosphorylation of ERK, JNK, and NF-κB, but not p38, was inhibited by rhinacanthin C, which also inhibited RANKL-stimulated TRAF6-TAK1 complex formation. Thus, the anti-osteoclastogenic effect of rhinacanthin C is mediated by a cascade of inhibition of RANKL-induced TRAF6-TAK1 association followed by activation of MAPKs/NF-κB; this leads to suppression of c-Fos and NFATc1, which regulate transcription of genes associated with osteoclast differentiation. In vivo, rhinacanthin C also reduced RANKL-induced osteoclast formation and bone resorption in mouse calvaria. Rhinacanthin C also suppressed LPS-stimulated osteoclastogenesis and bone resorption in vitro and in vivo. Rhinacanthin C may provide a novel therapy for abnormal bone lysis that occurs during inflammatory bone resorption. PMID:26083531

  10. 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.

  11. Integrating Phosphoproteome and Transcriptome Reveals New Determinants of Macrophage Multinucleation*

    PubMed Central

    Rotival, Maxime; Ko, Jeong-Hun; Srivastava, Prashant K.; Kerloc'h, Audrey; Montoya, Alex; Mauro, Claudio; Faull, Peter; Cutillas, Pedro R.; Petretto, Enrico; Behmoaras, Jacques

    2015-01-01

    Macrophage multinucleation (MM) is essential for various biological processes such as osteoclast-mediated bone resorption and multinucleated giant cell-associated inflammatory reactions. Here we study the molecular pathways underlying multinucleation in the rat through an integrative approach combining MS-based quantitative phosphoproteomics (LC-MS/MS) and transcriptome (high-throughput RNA-sequencing) to identify new regulators of MM. We show that a strong metabolic shift toward HIF1-mediated glycolysis occurs at transcriptomic level during MM, together with modifications in phosphorylation of over 50 proteins including several ARF GTPase activators and polyphosphate inositol phosphatases. We use shortest-path analysis to link differential phosphorylation with the transcriptomic reprogramming of macrophages and identify LRRFIP1, SMARCA4, and DNMT1 as novel regulators of MM. We experimentally validate these predictions by showing that knock-down of these latter reduce macrophage multinucleation. These results provide a new framework for the combined analysis of transcriptional and post-translational changes during macrophage multinucleation, prioritizing essential genes, and revealing the sequential events leading to the multinucleation of macrophages. PMID:25532521

  12. Orthodontic treatment in patient with idiopathic root resorption: A case report

    PubMed Central

    Rey, Diego; Smit, Rosana Martínez; Gamboa, Liliana

    2015-01-01

    Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results. PMID:25741832

  13. Orthodontic treatment in patient with idiopathic root resorption: a case report.

    PubMed

    Rey, Diego; Smit, Rosana Martínez; Gamboa, Liliana

    2015-01-01

    Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results. PMID:25741832

  14. Treatment of Internal Resorption with Mineral Trioxide Aggregates: A Case Report

    PubMed Central

    Yadav, Pankaj; Rao, Yogesh; Jain, Anurag; Relhan, Nikhil; Gupta, Sandeep

    2013-01-01

    Tooth resorption is a common sequel which follows injuries or irritation to the periodontal ligament and/or tooth pulp. The course of tooth resorption involves an elaborate interaction among inflammatory cells, resorbing cells, and hard tissue structures. The key cells which are involved in resorption are multi–nucleated giant cells. Internal root resorptions are usually non–symptomatic and they are discovered occasionally through periapical radiographs, which reveal very defined and regular outlines. Many techniques and materials have been used to fill internal resorptive defects. Among them, Mineral Trioxide Aggregates (MTAs) have satisfactory properties, which include: biocompatibility, a favourable sealing ability, mechanical strength and a capacity to promote a periradicular tissue healing. Thus, a Mineral Trioxide Aggregate (MTA) repair of a maxillary left central incisor tooth with an inflammatory resorptive defect, in the middle third of the root canal, has been reported here. PMID:24298543

  15. Treatment of internal resorption with mineral trioxide aggregates: a case report.

    PubMed

    Yadav, Pankaj; Rao, Yogesh; Jain, Anurag; Relhan, Nikhil; Gupta, Sandeep

    2013-10-01

    Tooth resorption is a common sequel which follows injuries or irritation to the periodontal ligament and/or tooth pulp. The course of tooth resorption involves an elaborate interaction among inflammatory cells, resorbing cells, and hard tissue structures. The key cells which are involved in resorption are multi-nucleated giant cells. Internal root resorptions are usually non-symptomatic and they are discovered occasionally through periapical radiographs, which reveal very defined and regular outlines. Many techniques and materials have been used to fill internal resorptive defects. Among them, Mineral Trioxide Aggregates (MTAs) have satisfactory properties, which include: biocompatibility, a favourable sealing ability, mechanical strength and a capacity to promote a periradicular tissue healing. Thus, a Mineral Trioxide Aggregate (MTA) repair of a maxillary left central incisor tooth with an inflammatory resorptive defect, in the middle third of the root canal, has been reported here. PMID:24298543

  16. Root Resorption a 6-Year Follow-up Case Report

    PubMed Central

    Dias, Caroline; Closs, Luciane; Barletta, Fernando; Reston, Eduardo; Tovo, Maximiano F; Lambert, Paula

    2015-01-01

    This paper describes the clinical course of a pediatric patient developing cervical external root resorption (CERR). An 11-year old male patient had sustained dental trauma and was diagnosed with crown fracture affecting the incisal and middle thirds of the maxillary right permanent central incisor and the maxillary right permanent lateral incisor with pulp exposure and CERR after 24 months. Diagnosis and treatment of CERR are a challenge for dental practitioners. In this case, preservation of natural dentition is shown as a successful treatment in a 6-year follow-up. PMID:25870717

  17. 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

  18. A Rare Case of Apical Root Resorption during Orthodontic Treatment of Patient with Multiple Aplasia.

    PubMed

    Agrawal, Chintan M; Mahida, Khyati; Agrawal, Charu C; Bothra, Jitendrakumar; Mashru, Ketan

    2015-07-01

    External apical root resorption is an adverse effect of orthodontic treatment. It reduces the length of root and breaks the integrity of teeth and dental arch. Orthodontics is the only dental specialty that clinically uses the inflammatory process to correct the mal-aligned teeth. Hence, it is necessary to know the risk factors of root resorption and do everything to reduce the rate of root resorption. Hence, all predisposing factors which are systemic as well as local should be considered before treatment begins. This case report describes the incidence of root resorption following orthodontic treatment and the teeth affected in the patient with multiple aplasia. PMID:26229386

  19. 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

  20. 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. PMID:26604965

  1. 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

  2. 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. PMID:26077784

  3. 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. PMID:25914241

  4. 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

  5. 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

  6. 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

  7. Locally administered T cells from mice immunized with lipopolysaccharide (LPS) accelerate LPS-induced bone resorption.

    PubMed

    Ozaki, Yukio; Ukai, Takashi; Yamaguchi, Masayuki; Yokoyama, Miho; Haro, Esperanza R Ayón; Yoshimoto, Mayumi; Kaneko, Takashi; Yoshinaga, Miho; Nakamura, Hirotaka; Shiraishi, Chiaki; Hara, Yoshitaka

    2009-06-01

    T cells play important roles in bone destruction and osteoclastogenesis and are found in chronic destructive bone lesions. Lipopolysaccharide (LPS) is one of several pathological factors involved in inflammatory bone destruction. We previously described the importance of T cells in the inflammatory bone resorption that occurs after repeated LPS administration. However, whether local or systemic T cells are important for inflammatory bone resorption and whether immunization of host animals influences bone resorption remain unclear. The present study examines the effects of local extant T cells from LPS-immunized mice on LPS-induced bone resorption. T cells from LPS-immunized or non-immunized mice were injected together with LPS into the gingival tissues of mice with severe combined immunodeficiency disease that lack both T and B cells. We histomorphometrically evaluated bone resorption at sites of T cell injections and examined the influence of T cells from LPS-immunized mice on osteoclastogenesis in vitro. We found that locally administered T cells from LPS-immunized but not non-immunized mice accelerated LPS-induced bone resorption in vivo. Moreover, T cells from LPS-immunized mice increased osteoclastogenesis in vitro induced by receptor activator of NF-kappa B ligand and LPS and anti-tumor necrosis factor (TNF)-alpha antibody inhibited this increase. These results demonstrated that local extant T cells accelerate inflammatory bone resorption. Furthermore, T cells from LPS-immunized mice appear to elevate LPS-induced bone resorption using TNF-alpha. PMID:19437611

  8. 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. PMID:17354446

  9. 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

  10. 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

  11. RNA therapeutics targeting osteoclast-mediated excessive bone resorption

    PubMed Central

    Wang, Yuwei; Grainger, David W

    2011-01-01

    RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare crisis as average life expectancy increases worldwide. New therapeutics are needed for this increasing patient population. This review describes the diversity of molecular targets suitable for RNAi-based gene knock-down in osteoclasts to control osteoclast-mediated excessive bone resorption. We identify strategies for developing targeted siRNA delivery and efficient gene silencing, and describe opportunities and challenges of introducing siRNA as a therapeutic approach to hard and connective tissue disorders. PMID:21945356

  12. 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

  13. Surgical intervention for treating an extensive internal resorption with unfavorable crown-to-root ratio

    PubMed Central

    Ashouri, Rezvan; Rekabi, Ali R; Parirokh, Masoud

    2012-01-01

    Internal resorption is a rare lesion in permanent teeth. Managing perforating internal resorption is a great challenge for dentists. This report presents a successful surgical treatment of a maxillary central incisor that had extensive root perforation due to internal resorption. After unsuccessful nonsurgical approach, during surgical intervention apical part of the resorption defect was removed and the coronal part was filled with mineral trioxide aggregate. Three years later the tooth was symptom free with normal mobility and pocket depth despite unfavorable crown-to-root ratio. This case report have shown that surgical intervention and using mineral trioxide aggregate as root canal filling material in a tooth with extensive internal resorption and unfavorable crown-to-root ratio can be considered as a treatment option. PMID:23112490

  14. 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

  15. 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

  16. Macrophage Autophagy in Atherosclerosis

    PubMed Central

    Maiuri, Maria Chiara; Grassia, Gianluca; Platt, Andrew M.; Carnuccio, Rosa; Ialenti, Armando; Maffia, Pasquale

    2013-01-01

    Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility. PMID:23401644

  17. 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

  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. “Internal root resorption: An endodontic challenge”: A case series

    PubMed Central

    Mittal, Sunandan; Kumar, Tarun; Mittal, Shifali; Sharma, Jyotika

    2014-01-01

    Management of internal root resorption is a challenge to the endodontists. It may occur in cases with chronic pulpal inflammation, following caries or due to trauma in the form of an accidental blow. Most cases of internal root resorption are seen in anterior teeth, due to their susceptibility to trauma. However, it may be seen in posterior teeth, most likely because of carious involvement of the pulp. Early diagnosis, removal of the cause, proper treatment of the resorbed root is mandatory for successful treatment outcome. This paper is an attempt to summarize the knowledge on internal root resorption and present various cases, which were successfully managed with different treatment modalities. PMID:25506152

  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. Macrophage Inflammatory Assay

    PubMed Central

    Ylostalo, Joni H.

    2016-01-01

    Macrophages represent a widely distributed and functionally diverse population of innate myeloid cells involved in inflammatory response to pathogens, tissue homeostasis and tissue repair (Murray and Wynn, 2011). Macrophages can be broadly grouped into two subpopulations with opposing activites: M1 or pro-inflammatory macrophages that promote T-helper type 1 (Th1) cell immunity and tissue damage, and M2 or anti-inflammatory/alternatively activated macrophages implicated in Th2 response and resolution of inflammation. Here we describe a rapid assay we used previously to monitor changes in pro-inflammatory and anti-inflammatory cytokine production by lipopolysaccharide (LPS)-activated macrophages in response to therapeutic paracrine factors produced by adult stem cells (Bartosh et al., 2010; Ylostalo et al., 2012; Bartosh et al., 2013). The assay can be adapted appropriately to test macrophage response to other agents as well that will be referred to herein as ‘test reagents’ or ‘test compounds’. In this protocol, the mouse macrophage cell line J774A.1 is expanded as an adherent monolayer on petri dishes allowing for the cells to be harvested easily without enzymes or cell scrapers that can damage the cells. The macropahges are then stimulated in suspension with LPS and seeded into 12-well cell culture plates containing the test reagents. After 16–18 h, the medium conditioned by the macrophages is harvested and the cytokine profile in the medium determined with enzyme-linked immunosorbent assays (ELISA). We routinely measure levels of the pro-inflammtory cytokine TNF-alpha and the anti-inflammatory cytokine interleukin-10 (IL-10).

  2. The Elusive Antifibrotic Macrophage.

    PubMed

    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

  3. Macrophage polarization in pathology.

    PubMed

    Sica, Antonio; Erreni, Marco; Allavena, Paola; Porta, Chiara

    2015-11-01

    Macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process continuing throughout adult life. Although present essentially in every organ/tissue, macrophages are more abundant in the gastro-intestinal tract, liver, spleen, upper airways, and brain. They have phagocytic and bactericidal activity and produce inflammatory cytokines that are important to drive adaptive immune responses. Macrophage functions are settled in response to microenvironmental signals, which drive the acquisition of polarized programs, whose extremes are simplified in the M1 and M2 dichotomy. Functional skewing of monocyte/macrophage polarization occurs in physiological conditions (e.g., ontogenesis and pregnancy), as well as in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer) and is now considered a key determinant of disease development and/or regression. Here, we will review evidence supporting a dynamic skewing of macrophage functions in disease, which may provide a basis for macrophage-centered therapeutic strategies. PMID:26210152

  4. Pulmonary Macrophage Transplantation Therapy

    PubMed Central

    Suzuki, Takuji; Arumugam, Paritha; Sakagami, Takuro; Lachmann, Nico; Chalk, Claudia; Sallese, Anthony; Abe, Shuichi; Trapnell, Cole; Carey, Brenna; Moritz, Thomas; Malik, Punam; Lutzko, Carolyn; Wood, Robert E.; Trapnell, Bruce C.

    2014-01-01

    SUMMARY Bone marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection-risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independent of hematologic progenitors prompted us to consider organ-targeted, cell-specific therapy. Here, using GM-CSF receptor-β deficient (Csf2rb−/−) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA/CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe, well-tolerated, and that one administration corrected the lung disease, secondary systemic manifestations, normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Results identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP. PMID:25274301

  5. 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

  6. Dual Effect of Chrysanthemum indicum Extract to Stimulate Osteoblast Differentiation and Inhibit Osteoclast Formation and Resorption In Vitro

    PubMed Central

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

    2014-01-01

    The risk of bone-related diseases increases due to the imbalance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively. The goal in the development of antiosteoporotic treatments is an agent that will improve bone through simultaneous osteoblast stimulation and osteoclast inhibition without undesirable side effects. To achieve this goal, numerous studies have been performed to identify novel approaches using natural oriental herbs to treat bone metabolic diseases. In the present study, we investigated the effect of Chrysanthemum indicum extract (CIE) on the differentiation of osteoclastic and osteoblastic cells. CIE inhibited the formation of TRAP-positive mature osteoclasts and of filamentous-actin rings and disrupted the bone-resorbing activity of mature osteoclasts in a dose-dependent manner. CIE strongly inhibited Akt, GSK3β, and IκB phosphorylation in RANKL-stimulated bone marrow macrophages and did not show any effects on MAP kinases, including p38, ERK, and JNK. Interestingly, CIE also enhanced primary osteoblast differentiation via upregulation of the expression of alkaline phosphatase and the level of extracellular calcium concentrations during the early and terminal stages of differentiation, respectively. Our results revealed that CIE could have a potential therapeutic role in bone-related disorders through its dual effects on osteoclast and osteoblast differentiation. PMID:25530776

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

    PubMed

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

    2016-05-19

    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 and 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 and have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs and could "smartly" self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently. PMID:27153349

  8. Management of progressive apical root resorption 13 years after dental trauma and primary endodontic treatment.

    PubMed

    Machado, Ricardo; Tomazinho, Luiz Fernando; Magagnin, Roseani; Leal Silva, Emmanuel João Nogueira; Vansan, Luiz Pascoal

    2016-01-01

    Many studies have focused on the search for a restorative material with good sealing properties and biocompatibility for treatment of teeth with open apices and necrotic pulps, which can result from periradicular disease and root resorption. Mineral trioxide aggregate (MTA) has exhibited promising clinical results in retrograde fillings and pulpotomies as well as for treatment of root perforations, root resorptions, incomplete root formations, and pulpal necrosis. This case report describes the management of a progressive apical root resorption in a previously traumatized tooth that had been endodontically treated. Five years of clinical and radiographic follow-up demonstrated the clinical efficacy of MTA in limiting the inflammatory resorptive process and promoting apexification and regeneration of periradicular tissue. PMID:27367638

  9. LEPTIN REGULATION OF BONE RESORPTION BY THE SYMPATHETIC NERVOUS SYSTEM AND CART

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 (Adrb...

  10. Management of mucosal fenestration with external root resorption by multidisciplinary approach.

    PubMed

    Bharti, Ramesh; Chandra, Anil; Tikku, Aseem Prakash; Prasad, Veerendra; Shakya, Vijay Kumar; Singhal, Rameshweri

    2014-01-01

    Mucosal fenestration is a clinical condition in which the overlying gingiva is denuded and the root is exposed to the oral cavity. Invasive cervical resorption is an entirely uncommon entity and its aetiology is poorly understood. This case presents an invasive cervical resorption of maxillary right central incisor with fenestration at the cervical third of the tooth. The resorption area was chemomechanically debrided. It was then restored with Mineral Trioxide Aggregate over which pink glass ionomer cement (GC Fuji VII) was placed. Lateral pedicle flap was used to cover the fenestration. The resorptive defect was restored using tooth coloured restorative resin after removal of the pink glass ionomer cement. Orthodontic treatment was continued for correction of malocclusion. PMID:25301425

  11. 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

  12. 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

  13. 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

  14. 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. PMID:26670486

  15. 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.

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

    PubMed

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

    2014-02-01

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

  17. 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

  18. 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

  19. Macrophage Polarization in Inflammatory Diseases

    PubMed Central

    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. PMID:24910531

  20. 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

  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. 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.

  3. 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.

  4. [Effect of osthol on apoptosis and bone resorption of osteoclasts cultured in vitro].

    PubMed

    Ming, Lei-Guo; Wang, Ming-Gang; Chen, Ke-Ming; Zhou, Jian; Han, Gui-Qiu; Zhu, Rui-Qing

    2012-02-01

    This study is to investigate the effect of osthol on osteoclasts' activity, bone resorption as well as apoptosis in vitro, and explore the mechanism of osthol in preventing osteoporosis. Osteoclasts were separated from long-limb bones of new born rabbits, cultured in 24-well plate with glass slices and bone slices, and treated by 1 x 10(-5) mol x L(-1) osthol. Osteoclasts were identified by observing live cells with phase contrast microscope, HE staining, TRAP staining and toluidine blue staining of bone resorption pits. The numbers of bone resorption pits were counted as well as the surface area of bone resorption on bone slice. Osteoclasts were stained with acridine orange to detect the cell apoptosis. The ratio of apoptotic osteoclasts was observed under fluorescence microscope. The gene expression of RANKL, OPG, TRAP and p-JNK1/2 protein expression were examined using real time PCR and Western blotting, respectively. Comparing with the control group without osthol, the rates of apoptotic osteoclasts increased obviously and the number and area of bone resorption pits decreased evidently with 1 x 10(-5) mol x L(-1) osthol. There is significant difference between control group and experiment group treated by 1 x 10(-5) mol x L(-1) osthol. Therefore, the osthol through RANK+RANKL/TRAF6/Mkk/JNK signal pathway inhibits the osteoclasts activity, enhances osteoclasts apoptotic and inhibits the bone resorption. PMID:22512027

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

    SciTech Connect

    Xiang Wei

    2006-08-09

    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

  6. Albumin impregnated vascular grafts: albumin resorption and tissue reactions.

    PubMed

    Cziperle, D J; Joyce, K A; Tattersall, C W; Henderson, S C; Cabusao, E B; Garfield, J D; Kim, D U; Duhamel, R C; Greisler, H P

    1992-01-01

    This study aimed to determine the kinetics of albumin resorption from and the healing of two types of albumin impregnated Vasculour II (Bard Cardiovascular) Dacron grafts (ACG-A and ACG-B) using whole blood preclotted Vasculour II Dacron grafts (without albumin) as controls (PCC). Prostheses measuring 4 mm ID x 50 mm length were implanted in the aortoiliac position in 24 dogs (ACG-A n = 12, ACG-B n = 24, PCC n = 12) and explanted after 1, 2 4, and 6 months. Platelet count, platelet aggregometry to 10(-5) M ADP, prothrombin time (PT), and partial thromboplastin time (PTT) were determined preoperatively and at explantation. Sections of the explanted grafts were assayed for human albumin by immunohistochemical techniques utilizing a rabbit polyclonal mono-specific antibody for human albumin followed by the addition of a biotinylated goat anti-rabbit IgG. Immunoperoxidase staining was then performed using Avidin D horse-radish peroxidase. Histology of the grafts (light microscopy, scanning electron microscopy, and transmission electron microscopy) as well as percent thrombus free surface area (TFSA) by computerized planimetry were also determined. Seven of 48 grafts were occluded (85.4% patency) with no difference among the three groups. Platelet aggregometry was not predictive of graft patency. No change in PT or PTT occurred nor was there any difference among the three groups. Retained albumin was detected in every one-month explant but not beyond that time, with the sensitivity for detecting human albumin in this assay being 20 mg albumin per gram of Dacron. All ACG explants at one month revealed inner capsular fibrin coagula not present in PCC specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1388174

  7. 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

  8. Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

    PubMed Central

    Dacquin, Romain; Domenget, Chantal; Kumanogoh, Atsushi; Kikutani, Hitoshi; Jurdic, Pierre; Machuca-Gayet, Irma

    2011-01-01

    Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D −/− mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D −/− mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function. PMID:22046317

  9. 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

  10. 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

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

    PubMed

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

    2015-12-01

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

  12. The effects of low-level laser therapy on orthodontically induced root resorption.

    PubMed

    Altan, A Burcu; Bicakci, A Altug; Mutaf, H Ilhan; Ozkut, Mahmut; Inan, V Sevinc

    2015-11-01

    The aim of this study was to evaluate the preventive and/or reparative effects of low-level laser therapy (LLLT) on orthodontically induced inflammatory root resorption (OIIRR) in rats. Thirty rats were divided into four groups (short-term control (SC), short-term laser (SL), long-term control (LC), long-term laser (LL)). In all groups, the left first molar was moved mesially for 11 days. At the end of this period, the rats in groups SC and SL were killed in order to observe the resorption lacunas and to evaluate whether LLLT had any positive effect on root resorption. The groups LC and LL were remained for a healing period of 14 days in order to observe spontaneous repair of the resorption areas and investigate whether LLLT had reparative effects on root resorption. A Ga-Al-As diode laser (Doris, CTL-1106MX, Warsaw, Poland) with a wavelength of 820 nm was used. In SL group, the first molars were irradiated with the dose of 4.8 J/cm2 (50 mW, 12 s, 0.6 J) on every other day during force application. In LL group, the irradiation period was started on the day of appliance removal and the first molars were irradiated with the dose of 4.8 J/cm2 on every other day for the next 14 days. LLLT significantly increased the number of osteoblasts and fibroblasts, and inflammatory response in SL group in comparison with SC group (P = .001). The amount of resorption did not represent any difference between the two groups (P = .16). In LL group, LLLT significantly increased the number of fibroblasts and decreased the amount of resorption in comparison with LC group (P = .001; P = .02). Both parameters indicating the reparative and the resorptive processes were found to be increased by LLLT applied during orthodontic force load. LLLT applied after termination of the orthodontic force significantly alleyed resorption and enhanced/accelerated the healing of OIIRR. LLLT has significant reparative effects on OIIRR while it is not possible to say that it definitely has a

  13. Early detection and staging of spontaneous embryo resorption by ultrasound biomicroscopy in murine pregnancy

    PubMed Central

    2014-01-01

    Background Embryo resorption is a major problem in human medicine, agricultural animal production and in conservation breeding programs. Underlying mechanisms have been investigated in the well characterised mouse model. However, post mortem studies are limited by the rapid disintegration of embryonic structures. A method to reliably identify embryo resorption in alive animals has not been established yet. In our study we aim to detect embryos undergoing resorption in vivo at the earliest possible stage by ultra-high frequency ultrasound. Methods In a longitudinal study, we monitored 30 pregnancies of wild type C57BI/6 mice using ultra-high frequency ultrasound (30-70 MHz), so called ultrasound biomicroscopy (UBM). We compared the sonoembryology of mouse conceptuses under spontaneous resorption and neighbouring healthy conceptuses and correlated the live ultrasound data with the respective histology. Results The process of embryo resorption comprised of four stages: first, the conceptus exhibited growth retardation, second, bradycardia and pericardial edema were observed, third, further development ceased and the embryo died, and finally embryo remnants were resorbed by maternal immune cells. In early gestation (day 7 and 8), growth retardation was characterized by a small embryonic cavity. The embryo and its membranes were ill defined or did not develop at all. The echodensity of the embryonic fluid increased and within one to two days, the embryo and its cavity disappeared and was transformed into echodense tissue surrounded by fluid filled caverns. In corresponding histologic preparations, fibrinoid material interspersed with maternal granulocytes and lacunae filled with maternal blood were observed. In later stages (day 9–11) resorption prone embryos were one day behind in their development compared to their normal siblings. The space between Reichert’s membrane and inner yolk sac membrane was enlarged The growth retarded embryos exhibited bradycardia and

  14. Modulation of Osteoclastogenesis with Macrophage M1- and M2-Inducing Stimuli

    PubMed Central

    Jeganathan, Sujeeve; Fiorino, Cara; Naik, Urja; Sun, He song; Harrison, Rene E.

    2014-01-01

    Macrophages are generated through the differentiation of monocytes in tissues and they have important functions in innate and adaptive immunity. In addition to their roles as phagocytes, macrophages can be further differentiated, in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), into osteoclasts (multinucleated giant cells that are responsible for bone resorption). In this work, we set out to characterize whether various inflammatory stimuli, known to induce macrophage polarization, can alter the type of multinucleated giant cell obtained from RANKL differentiation. Following a four-day differentiation protocol, along with lipopolysaccharide (LPS)/interferon gamma (IFNγ) as one stimulus, and interleukin-4 (IL-4) as the other, three types of multinucleated cells were generated. Using various microscopy techniques (bright field, epifluorescence and scanning electron), functional assays, and western blotting for osteoclast markers, we found that, as expected, RANKL treatment alone resulted in osteoclasts, whereas the addition of LPS/IFNγ to RANKL pre-treated macrophages generated Langhans-type giant cells, while IL-4 led to giant cells resembling foreign body giant cells with osteoclast-like characteristics. Finally, to gain insight into the modulation of osteoclastogenesis, we characterized the formation and morphology of RANKL and LPS/IFNγ-induced multinucleated giant cells. PMID:25101660

  15. 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

  16. 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

  17. Notch2 signaling promotes osteoclast resorption via activation of PYK2.

    PubMed

    Jin, Won Jong; Kim, Bongjun; Kim, Jung-Wook; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2016-05-01

    Notch signaling plays a central role in various cell fate decisions, including skeletal development. Recently, Notch signaling was implicated in osteoclast differentiation and maturation, including the resorption activity of osteoclasts. However, the specific involvement of notch signaling in resorption activity was not fully investigated. Here, we investigated the roles of Notch signaling in the resorption activity of osteoclasts by use of the gamma-secretase inhibitor dibenzazepine (DBZ). Attenuating Notch signaling by DBZ suppressed the expression of NFATc1, a master transcription factor for osteoclast differentiation. However, overexpression of a constitutively active form of NFATc1 did not fully rescue the effects of DBZ. DBZ suppressed the autophosphorylation of PYK2, which is essential for the formation of the podosome belt and sealing zone, with reduced c-Src/PYK2 interaction. We found that RANKL increases PYK2 activation accompanied by increased NICD2 production in osteoclasts. Overexpression of NICD2 in osteoclasts rescued DBZ-mediated suppression of resorption activity with promotion of PYK2 autophosphorylation and microtubule acetylation. Consistent with the in vitro results, DBZ strongly suppressed bone destruction in an interleukin-1-induced bone loss model. Collectively, these results demonstrate that Notch2 in osteoclasts plays a role in the control of resorption activity via the PYK2-c-Src-microtubule signaling pathway. PMID:26829213

  18. 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

  19. 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

  20. 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. PMID:27104973

  1. 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

  2. MTA resorption and periradicular healing in an open-apex incisor: A case report

    PubMed Central

    Asgary, Saeed; Ehsani, Sara

    2011-01-01

    This case report describes the periradicular healing and resorption of an unintentional extrusion of mineral trioxide aggregate (MTA) in an open-apex central incisor. A 22-year old female with a symptomatic open-apex right maxillary central incisor associated with a periradicular lesion was referred for evaluation and treatment. After chemomechanical debridement, the apical third of the root canal was filled with MTA to create an apical plug. Postoperative radiographs showed the extrusion of MTA into the periradicular lesion. The tooth was then restored with a post and crown. At the 2-year follow-up, the tooth was asymptomatic and radiographs revealed complete healing of the periradicular area. At the 7-year follow-up, complete resorption of the extruded MTA was evident. The results of this case study indicate that complete resorption of extruded MTA is possible in the long term; however, the extrusion of MTA in open-apex tooth should still be avoided. PMID:23960529

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

    PubMed Central

    DEVKOTA, Bhuminad; TAKAHASHI, Masahiro; SATO, Saori; SASAKI, Kouya; UEKI, Atsushi; OSAWA, Takeshi; TAKAHASHI, Masahiro; YAMAGISHI, Norio

    2015-01-01

    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. PMID:25755022

  4. [Reducing bone resorption by cathepsin K inhibitor and treatment of osteoporosis].

    PubMed

    Watanabe, Reiko; Okazaki, Ryo

    2014-01-01

    Cathepsin K is a lysosomal cysteine protease, secreted from osteoclasts. It plays a major role in the osteoclastic bone resorption by cleaving type 1 collagen, the major bone matrix protein, under acidic pH. In cathepsin K knockout mice, bone mineral density (BMD) is increased, bone resorption is decreased without reduction in the number of osteoclast whereas bone formation is decreased. Based on these results, cathepsin K inhibitors have been developed for the treatment of osteoporosis. Odanacatib is one of them and is perhaps closest for launching. In phase 1 and 2 trials, it markedly reduced bone resorption with a transient reduction in bone formation, thus resulted in a robust increase in both trabecular and cortical BMD in osteoporotics. Currently, Odanacatib is in phase 3 fracture prevention trial, of which results are anticipated in 2014. PMID:24369281

  5. 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

  6. 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

  7. Local Mechanical Stimuli Regulate Bone Formation and Resorption in Mice at the Tissue Level

    PubMed Central

    Schulte, Friederike A.; Ruffoni, Davide; Lambers, Floor M.; Christen, David; Webster, Duncan J.; Kuhn, Gisela; Müller, Ralph

    2013-01-01

    Bone is able to react to changing mechanical demands by adapting its internal microstructure through bone forming and resorbing cells. This process is called bone modeling and remodeling. It is evident that changes in mechanical demands at the organ level must be interpreted at the tissue level where bone (re)modeling takes place. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the mechanoregulation of bone three-dimensionally by experiment. Using in vivo micro-computed tomography and high resolution finite element analysis in living mice, we show that bone formation most likely occurs at sites of high local mechanical strain (p<0.0001) and resorption at sites of low local mechanical strain (p<0.0001). Furthermore, the probability of bone resorption decreases exponentially with increasing mechanical stimulus (R2 = 0.99) whereas the probability of bone formation follows an exponential growth function to a maximum value (R2 = 0.99). Moreover, resorption is more strictly controlled than formation in loaded animals, and ovariectomy increases the amount of non-targeted resorption. Our experimental assessment of mechanoregulation at the tissue level does not show any evidence of a lazy zone and suggests that around 80% of all (re)modeling can be linked to the mechanical micro-environment. These findings disclose how mechanical stimuli at the tissue level contribute to the regulation of bone adaptation at the organ level. PMID:23637993

  8. Lithium chloride attenuates root resorption during orthodontic tooth movement in rats

    PubMed Central

    WANG, YU; GAO, SHANG; JIANG, HUAN; LIN, PENG; BAO, XINGFU; ZHANG, ZHIMIN; HU, MIN

    2014-01-01

    Root resorption is a common side effect of orthodontic treatment. In the current study, lithium chloride (LiCl), a Wnt signaling activator, was examined to determine its effect on root resorption. In total, 10 Sprague Dawley rats were randomly allocated into the experimental group (EG) and control group (CG). Each group consisted of five subjects. By using closed nickel-titanium coil springs, a 50-g force was applied between the upper incisors and the maxillary right first molars in order to mimic orthodontic biomechanics in the EG and CG for 14 days. During the 14 days, the EG rats were gavage-fed 200 mg/kg LiCl every 48 h. Next, digital radiographs were captured using a micro-computational tomography scanner. The movement of the maxillary first molars and the root resorption area ratio were measured electronically on the digital radiographs. The outcomes were analyzed using ANOVA. Following 14 days of experimental force application, all rats had spaces of varying sizes between the first and second right maxillary molars. The average distance measured in the CG was slightly higher than in the EG, however, the difference was not found to be statistically significant (P=0.224). Root resorption craters were observed in the groups following the experiment. Rough cementum areas were observed on the mesial surface of the distobuccal and distopalatal roots. The mean root resorption area ratio of CG was significantly greater than EG (P<0.05). Results of the present study indicate that LiCl can attenuate orthodontically induce root resorption during orthodontic tooth movement. The effect of LiCl on tooth movement is insignificant. PMID:24396427

  9. Macrophage infection models for Mycobacterium tuberculosis.

    PubMed

    Johnson, Benjamin K; Abramovitch, Robert B

    2015-01-01

    Mycobacterium tuberculosis colonizes, survives, and grows inside macrophages. In vitro macrophage infection models, using both primary macrophages and cell lines, enable the characterization of the pathogen response to macrophage immune pressure and intracellular environmental cues. We describe methods to propagate and infect primary murine bone marrow-derived macrophages and J774 and THP-1 macrophage-like cell lines. We also present methods on the characterization of M. tuberculosis intracellular survival and the preparation of infected macrophages for imaging. PMID:25779326

  10. 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

  11. Bradykinin stimulates bone resorption and lysosomal-enzyme release in cultured mouse calvaria.

    PubMed Central

    Gustafson, G T; Lerner, U

    1984-01-01

    The effect of bradykinin on bone resorption was studied in cultures of newborn-mouse calvaria. Bradykinin (0.03 microM, 1 microM) stimulated the release of 45Ca2+ from bones dissected out from mice prelabelled in vivo with 45Ca. Bradykinin (1 microM) also augmented the release of stable calcium ( 40Ca ), Pi and the lysosomal enzyme beta-glucuronidase. The stimulatory effect of bradykinin on mineral mobilization and lysosmal -enzyme release could be blocked by indomethacin. It is speculated that concomitant generation of thrombin and bradykinin in areas of trauma and inflammation may induce resorption of nearby bone tissue. PMID:6721862

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Macrophage immunoregulatory pathways in tuberculosis

    PubMed Central

    Rajaram, Murugesan V.S.; Ni, Bin; Dodd, Claire E.; Schlesinger, Larry S.

    2014-01-01

    Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs). PMID:25453226

  18. 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

  19. Treatment with Potassium Bicarbonate Lowers Calcium Excretion and Bone Resorption in Older Men and Women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies. The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and wom...

  20. [Topics for basic research(osteoclast and bone resorption)in ASBMR 2015].

    PubMed

    Udagawa, Nobuyuki

    2016-01-01

    This is a brief report summarizing topics in ASBMR 2015 held at Washington State Convention Center in Seattle on October 9-12th. In this paper, I report some topics from presentation of basic research(especially osteoclast and bone resorption)in ASBMR 2015. PMID:26728539

  1. 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...

  2. 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

  3. 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

  4. 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. PMID:25728818

  5. 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

  6. Voxel Size and Measures of Individual Resorption Cavities in Three-Dimensional Images of Cancellous Bone

    PubMed Central

    Tkachenko, E.V.; Slyfield, C.R.; Tomlinson, R.E.; Daggett, J.R.; Wilson, D.L.; Hernandez, C.J.

    2009-01-01

    Cavities formed by osteoclasts on the surface of cancellous bone during bone remodeling (resorption cavities) are believed to act as stress risers and impair cancellous bone strength and stiffness. Although resorption cavities are readily detected as eroded surfaces in histology sections, identification of resorption cavities in three-dimensional images of cancellous bone has been rare. Here we use sub-micron resolution images of rat lumbar vertebral cancellous bone obtained through serial milling (n=5) to determine how measures of the number and surface area of resorption cavities are influenced by image resolution. Three-dimensional images of a 1mm cube of cancellous bone were collected at 0.7 X 0.7 X 5.0 μm/voxel using fluorescence based serial milling and uniformly coarsened to four other resolutions ranging from 1.4 X 1.4 X 5.0 to 11.2 X 11.2 X 10 μm/voxel. Cavities were identified in the three-dimensional image as an indentation on the cancellous bone surface and were confirmed as eroded surfaces by viewing two-dimensional cross-sections (mimicking histology techniques). The number of cavities observed in the 0.7 X 0.7 X 5.0 μm/voxel images (22.0 ± 1.43, mean ± SD) was not significantly different from that in the 1.4 X 1.4 X 5.0 μm/voxel images (19.2 ± 2.59) and an average of 79% of the cavities observed at both of these resolutions were coincident. However, at lower resolutions, cavity detection was confounded by low sensitivity (<20%) and high false positive rates (>40%). Our results demonstrate that when image voxel size exceeds 1.4 X 1.4 X 5.0 μm/voxel identification of resorption cavities by bone surface morphology is highly inaccurate. Experimental and computational studies of resorption cavities in three-dimensional images of cancellous bone may therefore require images to be collected at resolutions of 1.4 μm/pixel in-plane or better to ensure consistent identification of resorption cavities. PMID:19482097

  7. 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

  8. 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.

  9. Bioelectric modulation of macrophage polarization

    PubMed Central

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

    2016-01-01

    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. PMID:26869018

  10. Bioelectric modulation of macrophage polarization.

    PubMed

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

    2016-01-01

    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. PMID:26869018

  11. 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

  12. The cellular actions of interleukin-11 on bone resorption in vitro.

    PubMed

    Hill, P A; Tumber, A; Papaioannou, S; Meikle, M C

    1998-04-01

    The pleiotropic cytokine interleukin-11 (IL-11) stimulates osteoclast formation in vitro, but it is not known whether it influences other steps in the bone-resorptive cascade. Using a variety of in vitro model systems for studying bone resorption we have investigated the effects of IL-11 on 1) osteoclast formation, fusion, migration, and activity; and 2) osteoblast-mediated osteoid degradation. The involvement of matrix metalloproteinases (MMPs) and products of arachidonic acid metabolism in IL-11-mediated resorption were also assessed. We first examined the bone-resorptive effects of IL-11 by assessing 45Ca release from neonatal mouse calvarial bones. IL-11 dose-dependently stimulated bone resorption with an EC50 of 10(-10) M. The kinetics of IL-11-mediated 45Ca release demonstrated that it was without effect for the first 48 h of culture, but by 96 h, it stimulated 45Ca release to the same level as that produced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (a hormone that stimulates osteoclast formation and activity). IL-11 also produced a dose-dependent increase in osteoblast-mediated type I collagen degradation with a maximum of 58.0 +/- 6.2% at 5 x 10(-9) M; this effect of IL-11 was less than that produced by 1,25-(OH)2D3 (76.5 +/- 7.1%) and was prevented by an inhibitor of MMPs, but not those blocking arachidonic acid metabolism. We then tested the effects of IL-11 on isolated mouse osteoclasts cultured on ivory slices in the presence and absence of primary mouse osteoblasts. IL-11 had no effect on isolated osteoclast activity even in coculture with primary osteoblasts. We then examined the effects of IL-11 on the formation of osteoclast-like multinucleate cells in mouse bone marrow cultures and the resorptive activity of such cultures using ivory as a substrate. IL-11 dose-dependently increased 1) the number of tartrate-resistant acid phosphatase-positive osteoclast-like multinucleate cells and 2) the surface area of lacunar resorption, although the effects

  13. 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

  14. 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

  15. 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.

  16. Calcium sensing and cell signaling processes in the local regulation of osteoclastic bone resorption.

    PubMed

    Zaidi, Mone; Moonga, Baljit S; Huang, Christopher L H

    2004-02-01

    The skeletal matrix in terrestrial vertebrates undergoes continual cycles of removal and replacement in the processes of bone growth, repair and remodeling. The osteoclast is uniquely important in bone resorption and thus is implicated in the pathogenesis of clinically important bone and joint diseases. Activated osteoclasts form a resorptive hemivacuole with the bone surface into which they release both acid and osteoclastic lysosomal hydrolases. This article reviews cell physiological studies of the local mechanisms that regulate the resorptive process. These used in vitro methods for the isolation, culture and direct study of the properties of neonatal rat osteoclasts. They demonstrated that both local microvascular agents and products of the bone resorptive process such as ambient Ca2+ could complement longer-range systemic regulatory mechanisms such as those that might be exerted through calcitonin (CT). Thus elevated extracellular [Ca2+], or applications of surrogate divalent cation agonists for Ca2+, inhibited bone resorptive activity and produced parallel increases in cytosolic [Ca2+], cell retraction and longer-term inhibition of enzyme release in isolated rat osteoclasts. These changes showed specificity, inactivation, and voltage-dependent properties that implicated a cell surface Ca2+ receptor (CaR) sensitive to millimolar extracellular [Ca2+]. Pharmacological, biophysical and immunochemical evidence implicated a ryanodine-receptor (RyR) type II isoform in this process and localized it to a unique, surface membrane site, with an outward-facing channel-forming domain. Such a surface RyR might function either directly or indirectly in the process of extracellular [Ca2+] sensing and in turn be modulated by cyclic adenosine diphosphate ribose (cADPr) produced by the ADP-ribosyl cyclase, CD38. The review finishes by speculating about possible detailed models for these transduction events and their possible interactions with other systemic mechanisms involved

  17. 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

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

    PubMed

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

    2014-10-01

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

  19. The role of macrophages in the biological reaction to wear debris from joint replacements

    PubMed Central

    Nich, Christophe; Goodman, Stuart B.

    2015-01-01

    Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene (PE) 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 lead 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

  20. Macrophages in Collateral Arteriogenesis

    PubMed Central

    Fung, Erik; Helisch, Armin

    2012-01-01

    Arteriosclerotic vascular disease is the most common cause of death and a major cause of disability in the developed world. Adverse outcomes of arteriosclerotic vascular disease are related to consequences of tissue ischemia and necrosis affecting the heart, brain, limbs, and other organs. Collateral artery growth or arteriogenesis occurs naturally and can help restore perfusion to ischemic tissues. Understanding the mechanisms of collateral artery growth may provide therapeutic options for patients with ischemic vascular disease. In this review, we examine the evidence for a role of monocytes and macrophages in collateral arteriogenesis. PMID:23055975

  1. 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

  2. Phosphatase regulation of macrophage activation.

    PubMed

    Kozicky, Lisa K; Sly, Laura M

    2015-08-01

    Macrophages are innate immune cells that play critical roles in tissue homeostasis and the immune response to invading pathogens or tumor cells. A hallmark of macrophages is their "plasticity," that is, their ability to respond to cues in their local microenvironment and adapt their activation state or phenotype to mount an appropriate response. During the inflammatory response, macrophages may be required to mount a profound anti-bacterial or anti-tumor response, an anti-inflammatory response, an anti-parasitic response, or a wound healing response. To do so, macrophages express cell surface receptors for growth factors, chemokines and cytokines, as well pathogen and danger associated molecular patterns. Downstream of these cell surface receptors, cell signalling cascades are activated and deactivated by reversible and competing activities of lipid and protein kinases and phosphatases. While kinases drive the activation of cell signalling pathways critical for macrophage activation, the strength and duration of the signalling is regulated by phosphatases. Hence, gene knockout mouse models have revealed critical roles for lipid and protein phosphatases in macrophage activation. Herein, we describe our current understanding and the key roles of specific cellular phosphatases in the regulation of the quality of macrophage polarization as well as the quantity of cytokines produced by activated macrophages. PMID:26216598

  3. 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

  4. 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

  5. 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.

  6. 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

  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

    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 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

  11. 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

  12. Asymptomatic, nonexpansile radiopacity of the jaw associated with external root resorption: a diagnostic dilemma.

    PubMed

    Mainville, Gisele N; Lalumière, Caroline; Turgeon, Daniel; Kauzman, Adel

    2016-01-01

    Incidental radiopacities of the jaws are commonly identified on routine intraoral and extraoral radiographs. Dentists should be able to develop a differential diagnosis of these lesions. This article presents 2 cases in which mandibular radiopacities associated with external root resorption were identified incidentally and discusses the differential diagnosis of these lesions. Both patients were referred by their general practitioners to dental specialists for further evaluation of homogenous osteosclerotic foci surrounding and resorbing the roots of the permanent mandibular right first molar. The lesions were asymptomatic, caused no cortical expansion, and were static over time. The clinical and radiographic features were consistent with a diagnosis of idiopathic osteosclerosis (IO). External root resorption is present in 10%-12% of cases of IO and often involves the permanent mandibular first molars. PMID:26742164

  13. 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.

  14. Histomorphometric Evaluation of Anorganic Bovine Bone Coverage to Reduce Autogenous Grafts Resorption: Preliminary Results

    PubMed Central

    Maiorana, Carlo; Beretta, Mario; Battista Grossi, Giovanni; Santoro, Franco; Scott Herford, Alan; Nagursky, Heiner; Cicciù, Marco

    2011-01-01

    Physiologic resorption due to remodeling processes affects autogenous corticocancellous grafts in the treatment of atrophic jawbone alveolar ridges. Such a situation in the past made overgrafting of the recipient site mandatory to get enough bone support to dental implants in order to perform a prosthetic rehabilitation. Anorganic bovine bone, conventionally used to treat alveolar bone deficiencies in implant surgery, showed a high osteoconductive property thanks to its micro and macrostructure very similar to that of human hydroxyapatite. An original technique provides for the application of a thin layer of anorganic bovine bone granules and a collagen membrane on the top of the corticocancellous onlay bone grafts to reduce in a remarkable way the graft resorption due to remodeling. The results of a clinical prospective study and a histomorphometric analysis done on autogenous grafts harvested from the iliac crest showed that the proposed technique is able to maintain the original bone volume of the corticocancellous blocks. PMID:21566694

  15. 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

  16. Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease.

    PubMed Central

    Chapman, H A; Allen, C L; Stone, O L; Fair, D S

    1985-01-01

    of plasminogen activator, these findings indicate that human alveolar macrophages normally synthesize and express measurable amounts of the initial enzymes of proteolytic reactions regulating both fibrin deposition and fibrin resorption. Abnormalities in Factor VII activity in a small group of patients with sarcoidosis raise the possibility that modulation of fibrin turnover by macrophages may contribute to the pathology of this and perhaps other interstitial lung diseases. Images PMID:4008651

  17. Spontaneous resorption of calcification at the long head of the biceps tendon

    PubMed Central

    Amri, Adriansyah; Nakai, Sho; Hara, Michiharu; Yamanaka, Issei; Hamawaki, Jun-ichi

    2015-01-01

    Calcific tendinitis of the long head of the biceps tendon is a rare cause of shoulder pain. Calcium deposits are often spontaneously resorbed or reduced in size in the rotator cuff tendons, which represent the most common sites of calcific tendinitis around the shoulder. To our knowledge, no case of spontaneous resorption of calcification in the long head of the biceps tendon has been reported in the literature. Here, we report one such case and describe its successful treatment using a conservative approach.

  18. 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

  19. 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

  20. Bisphosphonates act on rat bone resorption through the mediation of osteoblasts.

    PubMed Central

    Sahni, M; Guenther, H L; Fleisch, H; Collin, P; Martin, T J

    1993-01-01

    Bisphosphonates are generally considered to act on bone resorption by binding to bone mineral and subsequently inhibiting the activity of the osteoclasts which ingest them. This has been supported by the fact that bisphosphonates adsorbed on mineralized tissue inhibit the resorbing activity of isolated osteoclasts in vitro. However, the effectiveness of different bisphosphonates determined in this system does not reflect their relative potencies in vivo. Employing the well-described isolated osteoclast resorption pit assay, with ivory as the resorption substrate, we show here that this lack of correlation prevails only when the bisphosphonates are added to the mineral before addition of osteoclasts, but not when the cells are treated for a short time (5 min) before allowing them to adhere onto ivory. By using this approach with five different bisphosphonates, a stringent correlation of relative potencies was obtained with those found, both in the rat and in the human, in vivo. Furthermore, by using an osteoblastic cell line (CRP 10/30) which is a powerful promoter of osteoclastic resorption in vitro, we obtained evidence that the inhibitory effect of bisphosphonates was the result of an action on osteoblasts rather than on osteoclasts. Thus, in experiments in which the osteoblastic cells were pretreated for 5 min with bisphosphonates and then cocultured with osteoclasts, inhibition of osteoclastic resorbing activity was obtained. Moreover, it was found that this treatment resulted in a decrease of the stimulatory effect found in CRP 10/30-conditioned medium. In conclusion the present study shows that part of the osteoclast inhibiting action of the bisphosphonates is mediated through an action on osteoblasts. Images PMID:8486770

  1. 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

  2. [Inhibitory effect of 8-prenylnaringenin on osteoclastogensis of bone marrow cells and bone resorption activity].

    PubMed

    Lü, Xiang; Zhou, Ying; Chen, Ke-Ming; Zhao, Zhi; Zhou, Jian; Ma, Xiao-Ni

    2013-03-01

    This study is to investigate the effect of 8-prenylnaringenin (8-PNG) on osteoclastogensis of bone marrow cells and bone resorption activity of osteoclasts. Osteoclasts were separated from long bone marrow of newborn rabbits and cultured in alpha-MEM containing 10% FBS. 8-PNG was added into culture media at 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) mol xL(-1), separately. 17beta-Estradiol (E2, 1 x 10(-7) mol x L(-7)) was used as positive control. T RAP staining and TRAP activity measurement were performed after 5 days, and the bone resorption pits were analyzed after 7 days. Annexin V staining for the detection of apoptotic osteoclasts was performed after 2, 4, 8, 12, 24, 36 and 48 h separately. The mRNA expression level of TRAP and cathepsin K (CTSK) was measured by real-time RT-PCR. 8-PNG significantly reduced the number of osteoclasts which was TRAP staining positive and with more than three nucleus, the area and number of bone resorption pits decreased obviously in 8-PNG-supplemented groups. The apoptosis rate peaked earlier in the 8-PNG-supplemented groups and the mRNA expression level of TRAP and CTSK decreased significantly. All these inhibitory effects were in a dose dependent manner, the highest effect was obtained by 1 x 10(-5) mol x L(-1) 8-PNG. 8-PNG inhibits bone resorption activity of osteoclasts by inducing osteoclast apoptosis and inhibiting the gene expression and enzyme activity including TRAP and CTSK, and restrains bone marrow cells to osteoclast differentiation. PMID:23724646

  3. 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.

  4. 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

  5. Effect of calvarial burring on resorption of onlay cranial bone graft.

    PubMed

    Hassanein, Aladdin H; Clune, James E; Mulliken, John B; Arany, Praveen R; Rogers, Gary F; Kulungowski, Ann M; Greene, Arin K

    2012-09-01

    Variable resorption occurs whenever calvarial bone graft is used for onlay cranioplasty. The recipient ectocortex may be burred to expose vessels and osteocytes to maximize healing. The purpose of this study was to determine whether abrading the recipient site improves the volume of onlay graft. The parietal bones of 17 rabbits were sectioned into split-thickness and full-thickness grafts. The right frontal cortex was abraded with a bur to punctate bleeding. Pairs of split-thickness (n = 48) or full-thickness (n = 20) grafts were onlayed to the burred right frontal bone and to the nonburred left frontal bone. Micro-computed tomography was used to determine graft volume immediately postoperatively and 16 weeks later. Histology, including tartrate-resistant acid phosphatase staining, was performed to quantify vascular channels and osteoclasts per high-power field 10 days postoperatively. Split-thickness graft volume decreased 58.0% when placed on the burred calvarial site, compared with grafts on the nonburred cortex (28.4%) (P = 0.01). Full-thickness grafts showed a similar trend: greater resorption (39.1%) when onlayed onto abraded calvaria compared with nonburred ectocortex (26.0%) (P = 0.11). Split-thickness graft orientation (cortical vs cancellous side in contact with the recipient site) did not affect resorption (P = 0.67). Onlay grafts placed on the burred recipient site had more vascular channels (11.8) and osteoclasts (5.7), compared with grafts over nonabraded cortex (3.4 and 4.2, respectively) (P < 0.05). Burring the recipient site cortex before onlay cranial bone grafting promotes resorption, possibly by increasing vascularization and osteoclastic activity. This technique cannot be recommended. PMID:22976644

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. Dietary xylitol, sorbitol and D-mannitol but not erythritol retard bone resorption in rats.

    PubMed

    Mattila, P T; Svanberg, M J; Mäkinen, K K; Knuuttila, M L

    1996-07-01

    The aim of the present study was to compare the ability of four dietary polyols to reduce bone resorption. Urinary excretion of 3H radioactivity from [3H]tetracycline-prelabeled rats was used as a marker of bone resorption. After prelabeling, the rats were divided randomly into five groups of 10, and fed for 1 mo a nonpurified diet that was supplemented in four groups with either xylitol, sorbitol, D-mannitol or erythritol, respectively, to give a polyol concentration of 1 mol/kg. Xylitol (42%), sorbitol (44%) and to a lesser degree D-mannitol (23%) decreased the excretion of 3H relative to the basal diet. The erythritol group, however, did not differ from the controls. Sorbitol caused continuous diarrhea, whereas in the other groups, intestinal adaptation took place during the 1st wk of polyol feeding. In conclusion, dietary xylitol, sorbitol and to a lesser degree D-mannitol supplementations in rats retard bone resorption, whereas dietary erythritol has no effect. PMID:8683349

  12. Hajdu Cheney Mouse Mutants Exhibit Osteopenia, Increased Osteoclastogenesis, and Bone Resorption.

    PubMed

    Canalis, Ernesto; Schilling, Lauren; Yee, Siu-Pok; Lee, Sun-Kyeong; Zanotti, Stefano

    2016-01-22

    Notch receptors are determinants of cell fate and function and play a central role in skeletal development and bone remodeling. Hajdu Cheney syndrome, a disease characterized by osteoporosis and fractures, is associated with NOTCH2 mutations resulting in a truncated stable protein and gain-of-function. We created a mouse model reproducing the Hajdu Cheney syndrome by introducing a 6955C→T mutation in the Notch2 locus leading to a Q2319X change at the amino acid level. Notch2(Q2319X) heterozygous mutants were smaller and had shorter femurs than controls; and at 1 month of age they exhibited cancellous and cortical bone osteopenia. As the mice matured, cancellous bone volume was restored partially in male but not female mice, whereas cortical osteopenia persisted in both sexes. Cancellous bone histomorphometry revealed an increased number of osteoclasts and bone resorption, without a decrease in osteoblast number or bone formation. Osteoblast differentiation and function were not affected in Notch2(Q2319X) cells. The pre-osteoclast cell pool, osteoclast differentiation, and bone resorption in response to receptor activator of nuclear factor κB ligand in vitro were increased in Notch2(Q2319X) mutants. These effects were suppressed by the γ-secretase inhibitor LY450139. In conclusion, Notch2(Q2319X) mice exhibit cancellous and cortical bone osteopenia, enhanced osteoclastogenesis, and increased bone resorption. PMID:26627824

  13. 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

  14. Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy.

    PubMed

    Téllez-Rojo, Martha María; Hernández-Avila, Mauricio; Lamadrid-Figueroa, Héctor; Smith, Donald; Hernández-Cadena, Leticia; Mercado, Adriana; Aro, Antonio; Schwartz, Joel; Hu, Howard

    2004-10-01

    The authors tested the hypotheses that maternal bone lead burden is associated with increasing maternal whole blood and plasma lead levels over the course of pregnancy and that this association is modified by rates of maternal bone resorption. A total of 193 Mexican women were evaluated (1997-1999) in the first, second, and third trimesters of pregnancy. Whole blood lead and plasma lead levels were measured in each trimester. Urine was analyzed for cross-linked N-telopeptides (NTx) of type I collagen, a biomarker of bone resorption. Patella and tibia lead levels were measured at 4 weeks postpartum. The relation between whole blood, plasma, and bone lead and NTx was assessed using mixed models. Plasma lead concentrations followed a U-shape, while NTx levels increased significantly during pregnancy. In a multivariate model, the authors observed a significant and positive interaction between NTx and bone lead when plasma lead was used as the outcome variable. Dietary calcium intake was inversely associated with plasma lead. Results for whole blood lead were similar but less pronounced. These results confirm previous evidence that bone resorption increases during pregnancy, with a consequential significant release of lead from bone, constituting an endogenous source of prenatal exposure. They also provide a rationale for testing strategies (e.g., nutritional supplementation with calcium) aimed at decreasing prenatal lead exposure. PMID:15383411

  15. Cytokine-mediated bone resorption is cytochrome P-450 dependent. Student Research Award 1998.

    PubMed

    Young, N; Chole, R

    1999-12-01

    Localized bone loss leads to much of the morbidity of chronic otitis media. Although the cellular events of bone remodeling have been well established, their regulation remains poorly understood. Various cytokines, including tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, used alone and in combination, are powerful inducers of bone resorption. One of the modulators of cytokine-induced bone resorption is nitric oxide (NO), a product of the action of NO synthase (NOS) on L -arginine to form NO. Cytochrome P-450, an enzyme that is similar to NOS both structurally and functionally, may also have a role in NO production in various cellular systems. The goal of this study was to elucidate a possible role of cytochrome P-450 in bone. In this study cytokine-induced bone resorption was blocked with cimetidine and clotrimazole, which are selective inhibitors of the cytochrome P-450 IIIA family and 7-ethoxyresorufin, a nonspecific cytochrome P-450 inhibitor. A concomitant reduction of NO was also observed. This effect may be explained by cytochrome P-450 being a preferred alternative pathway or providing an essential cofactor to NOS in bone. PMID:10580224

  16. Injectable bone substitute to preserve alveolar ridge resorption after tooth extraction: a study in dog

    PubMed Central

    Boix, Damien; Weiss, Pierre; Gauthier, Olivier; Guicheux, Jérôme; Bouler, Jean-Michel; Pilet, Paul; Daculsi, Guy; Grimandi, Gaël

    2006-01-01

    The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute on the prevention of alveolar ridge resorption after tooth extraction. Maxillary and mandibular premolars were extracted from 3 Beagle dogs with preservation of alveolar bone. Thereafter, distal sockets were filled with an injectable bone substitute (IBS), obtained by combining a polymer solution and granules of a biphasic calcium phosphate (BCP) ceramic. As a control, the mesial sockets were left unfilled. After a 3 months healing period, specimens were removed and prepared for histomorphometric evaluation with image analysis. Histomorphometric study allowed to measure the mean and the maximal heights of alveolar crest modifications. Results always showed an alveolar bone resorption in unfilled sockets. Resorption in filled maxillary sites was significantly lower than in control sites. Interestingly, an alveolar ridge augmentation was measured in mandibular filled sockets including 30 % of newly-formed bone. It was concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate can significantly increase alveolar ridge preservation after tooth extraction. PMID:17122930

  17. 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

  18. Conservative Nonsurgical Treatment of Class 4 Invasive Cervical Resorption: A Case Series.

    PubMed

    Salzano, Stefano; Tirone, Federico

    2015-11-01

    External cervical resorption, also called invasive cervical resorption (ICR), is a pathological process difficult to diagnose that causes a progressive replacement of dentin by granulation tissue and results in complete tooth destruction. According to the literature, class 4 ICR can be expected to have success rates of 12.5% if treated. In this case series, we show nonsurgical conservative treatment of 4 patients affected by class 4 ICR. In 4 patients affected by class 4 ICRs, granulomatous tissue was orthograde removed with the help of an operating microscope and cone-beam computed tomographic imaging. The teeth were devitalized, the granulomatous tissue was mechanically removed, and the defects were filled with either mineral trioxide aggregate or Biodentine (Septodont, Saint-Maur-des-Fossés, France). After a follow-up period varying from 18 months for case 1 to 4 months for case 4, neither signs of periradicular bone rarefaction nor recurrence of resorption were observed. The teeth were asymptomatic, and conservative restorations appeared to be in excellent condition. Given the results achieved in this case series, it may be assumed that many class 4 ICRs could be successfully treated with the help of an operating microscope and cone-beam computed tomographic imaging. PMID:26395913

  19. 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

  20. 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

  1. Revascularization Technique for the Treatment of External Inflammatory Root Resorption: A Report of 3 Cases.

    PubMed

    Santiago, Cristina N; Pinto, Shirley S; Sassone, Luciana M; Hirata, Raphael; Fidel, Sandra R

    2015-09-01

    The current external inflammatory root resorption treatment protocol, which uses calcium hydroxide dressing, usually comprises multiple and long-term applications. In addition to the need for multiple appointments for calcium hydroxide replacement, the long-term maintenance of this compound in the root canal weakens dental structures. A modification of this therapy would be advisable. In this clinical investigation, 3 patients with external inflammatory root resorption were submitted to revascularization therapy protocol usually used in teeth with necrotic pulp and open apices. The teeth were treated with revascularization therapy protocol, which consisted of disinfecting the root canal system with triantibiotic paste, filling it with blood clot, and sealing of the root canal with mineral trioxide aggregate and bonded resin restoration. During the follow-up, the pathologic process was arrested with tissue repair in pre-existing radiolucent areas. Reduced mobility was observed in the treated teeth. The 3 cases were followed up for 30, 18, and 15 months, respectively. All teeth remained asymptomatic and retained function and physiological mobility. The therapy used in the revascularization procedure was efficient in the treatment of external inflammatory root resorption, reducing the number of appointments and increasing patient compliance. PMID:26074180

  2. [Decoronation: treatment protocol for ankylotic root resorption as a consequence of dental trauma].

    PubMed

    Lin, S; Fuss, Z; Wigler, R; Karawani, M; Ashkenazi, M

    2013-10-01

    Severe dental traumatic injuries, such as the complete displacement of a tooth from its socket (Avulsion) or the displacement of a tooth within its socket (Intrusive Luxation), may result in extensive injury to the root surface. As a result, the root surface injury heals without cementum and there is fusion between the alveolar bone and the exposed dentin or anorganic exposed cementum, without any attachment apparatus between them. This phenomenon is known as "dento-alveolar ankylosis" and is accompanied by ankylotic resorption of the root. In a process that results subsequent to the ankylosis, the root surface resorbs, and this is part of the remodeling of the alveolar bone (ankylotic resorption). When the traumatic injury occurs at a young age, lateral and apical growth of the alveolar bone continues without continued physiological eruption of the tooth. As a result, the position of the ankylotic tooth does not change, and with time thetooth appears infra-occluded resulting in severe esthetic and functional consequences. Extraction of the ankylotic tooth is difficult and sometimes even impossible due to the rigid fusion between the bone and the tooth. In addition, attempted extraction of the ankylotic tooth may lead to fracture of the buccal plate and resorption of the alveolar bone. Retention of the ankylotic tooth may lead to damage in bone deposition in the verticaldimension, leading to difficulties in future prosthodonticrehabilitation, research-based information has been incorporated PMID:24660573

  3. Comparison of growth-induced resorption and denervation-induced resorption on the release of (/sup 3/H)tetracycline, /sup 45/calcium, and (/sup 3/H)collagen from whole bones of growing rats

    SciTech Connect

    Klein, L.; Heiple, K.G.; Stromberg, B.V.

    1983-01-01

    The major effect of immobilization during growth is a smaller bone mass induced by either an increased bone resorption or a decreased bone formation. Using a method of analyzing radioisotopic loss of (/sup 3/H)tetracycline and (/sup 3/H)collagen from bone prelabeled in vivo, we compared the amount of bone resorption due to immobilization with bone resorption induced by growth. One hind limb was denervated in growing male rats, 6 weeks of age, that had been chronically prelabeled with (/sup 3/H)tetracycline, /sup 45/calcium, and (/sup 3/H)proline. The total radioactivity of the whole femur and tibia/fibula from the denervated limb was compared with that from bones of the control limb at 0, 1, 2, 4, and 8 weeks after denervation. The effect of growth on bone formation was measured by net increases in bone length, volume, and mass of matrix and mineral. Experimental bones had a significantly smaller volume and mass. Bone resorption was much greater during growth modeling than during denervation. The additional bone resorption induced by denervation was a small fraction (one-fourth) of the resorption induced by growth. Denervation during growth resulted in less bone being formed due to a smaller gain in matrix and mineral mass as a result of a reduction in bone formation.

  4. 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

  5. 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

  6. A theory for bone resorption based on the local rupture of osteocytes cells connections: A finite element study.

    PubMed

    Ridha, Hambli; Almitani, Khalid H; Chamekh, Abdessalem; Toumi, Hechmi; Tavares, Joao Manuel R S

    2015-04-01

    In this work, a bone damage resorption finite element model based on the disruption of the inhibitory signal transmitted between osteocytes cells in bone due to damage accumulation is developed and discussed. A strain-based stimulus function coupled to a damage-dependent spatial function is proposed to represent the connection between two osteocytes embedded in the bone tissue. The signal is transmitted to the bone surface to activate bone resorption. The proposed model is based on the idea that the osteocyte signal reduction is not related to the reduction of the stimulus sensed locally by osteocytes due to damage, but to the difficulties for the signal in travelling along a disrupted area due to microcracks that can destroy connections of the intercellular network between osteocytes and bone-lining cells. To check the potential of the proposed model to predict the damage resorption process, two bone resorption mechano-regulation rules corresponding to two mechanotransduction approaches have been implemented and tested: (1) Bone resorption based on a coupled strain-damage stimulus function without ruptured osteocyte connections (NROC); and (2) Bone resorption based on a strain stimulus function with ruptured osteocyte connections (ROC). The comparison between the results obtained by both models, shows that the proposed model based on ruptured osteocytes connections predicts realistic results in conformity with previously published findings concerning the fatigue damage repair in bone. PMID:25640868

  7. 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

  8. 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.

  9. Bone resorption facilitates osteoblastic bone metastatic colonization by cooperation of insulin-like growth factor and hypoxia.

    PubMed

    Kuchimaru, Takahiro; Hoshino, Takuya; Aikawa, Tomoya; Yasuda, Hisataka; Kobayashi, Tatsuya; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae

    2014-05-01

    Bone metastasis is a multistep process that includes cancer cell dissemination, colonization, and metastatic growth. Furthermore, this process involves complex, reciprocal interactions between cancer cells and the bone microenvironment. Bone resorption is known to be involved in both osteolytic and osteoblastic bone metastasis. However, the precise roles of the bone resorption in the multistep process of osteoblastic bone metastasis remain unidentified. In this study, we show that bone resorption plays important roles in cancer cell colonization during the initial stage of osteoblastic bone metastasis. We applied bioluminescence/X-ray computed tomography multimodal imaging that allows us to spatiotemporally analyze metastasized cancer cells and bone status in osteoblastic bone metastasis models. We found that treatment with receptor activator of factor-κB ligand (RANKL) increased osteoblastic bone metastasis when given at the same time as intracardiac injection of cancer cells, but failed to increase metastasis when given 4 days after cancer cell injection, suggesting that RANKL-induced bone resorption facilitates growth of cancer cells colonized in the bone. We show that insulin-like growth factor-1 released from the bone during bone resorption and hypoxia-inducible factor activity in cancer cells cooperatively promoted survival and proliferation of cancer cells in bone marrow. These results suggest a mechanism that bone resorption and hypoxic stress in the bone microenvironment cooperatively play an important role in establishing osteoblastic metastasis. PMID:24597654

  10. In-Vivo Effect of Andrographolide on Alveolar Bone Resorption Induced by Porphyromonas gingivalis and Its Relation with Antioxidant Enzymes

    PubMed Central

    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. PMID:24151590