Дисертації з теми "Bone resorption"
Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Bone resorption.
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "Bone resorption".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Pierce, Angela Mary. "Cellular mechanisms in bone and tooth resorption morphological studies in rats and monkeys /." Stockholm : Kongl. Carolinska Medico Chirurgiska Institutet, 1988. http://books.google.com/books?id=usBpAAAAMAAJ.
2
Heath, J. K. "Studies on cellular interactions in bone resorption." Thesis, Anglia Ruskin University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354876.
3
McCauley, Laurie Kay. "Cellular mechanisms of lymphocyte-mediated bone resorption /." The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487759055156174.
4
Stutzer, Andre. "Retinoid induced bone resorption, model and application /." [S.l.] : [s.n.], 1987. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
5
Ransjö, Maria. "Regulation of bone resorption by the adenylate cyclase-cyclic AMP system a biochemical study on mouse calvarial bones and isolated bone cells /." Umeå, Sweden : University of Umeå, 1988. http://catalog.hathitrust.org/api/volumes/oclc/18171035.html.
6
Bernhold, Brechter Anna. "Kinins : important regulators in inflammation induced bone resorption." Doctoral thesis, Umeå : Univ, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-959.
7
Moroz, Adam. "Reduced order modelling of bone resorption and formation." Thesis, De Montfort University, 2011. http://hdl.handle.net/2086/5409.
Анотація:
The bone remodelling process, performed by the Bone Multicellular Unit (BMU) is a key multi-hierarchically regulated process, which provides and supports various functionality of bone tissue. It is also plays a critical role in bone disorders, as well as bone tissue healing following damage. Improved modelling of bone turnover processes could play a significant role in helping to understand the underlying cause of bone disorders and thus develop more effective treatment methods. Moreover, despite extensive research in the field of bone tissue engineering, bonescaffold development is still very empirical. The development of improved methods of modelling the bone remodelling process should help to develop new implant designs which encourage rapid osteointegration. There are a number of limitations with respect to previous research in the field of mathematical modelling of the bone remodelling process, including the absence of an osteocyte loop of regulation. It is within this context that this research presented in this thesis utilises a range of modelling methods to develop a framework for bone remodelling which can be used to improve treatment methods for bone disorders. The study concentrated on dynamic and steady state variables that in perspective can be used as constraints for optimisation problem considering bone remodelling or tissue remodelling with the help of the grafts/scaffolds.The cellular and combined allosteric-regulation approaches to modelling of bone turnover, based on the osteocyte loop of regulation, have been studied. Both approaches have been studied different within wide range of rate parameters. The approach to the model validation has been considered, including a statistical approach and parameter reduction approach. From a validation perspective the cellular class of modes is preferable since it has fewer parameters to validate. The optimal control framework for regulation of remodelling has been studied. Future work in to improve the models and their application to bone scaffold design applications have been considered. The study illustrates the complexity of formalisation of the metabolic processes and the relations between hierarchical subsystems in hard tissue where a relatively small number of cells are active. Different types/modes of behaviour have been found in the study: relaxational, periodical and chaotic modes. All of these types of behaviour can be found, in bone tissue. However, a chaotic or periodic modes are ones of the hardest to verify although a number of periodical phenomena have been observed empirically in bone and skeletal development. Implementation of the allosteric loop into cellular model damps other types of behaviour/modes. In this sense it improves the robustness, predictability and control of the system. The developed models represent a first step in a hierarchical model of bone tissue (system versus local effects). The limited autonomy of any organ or tissue implies differentiation on a regulatory level as well as physiological functions and metabolic differences. Implementation into the cellular phenomenological model of allosteric-like loop of regulation has been performed. The results show that the robustness of regulation can be inherited from the phenomenological model. An attempt to correlate the main bone disorders with different modes of behaviour has been undertaken using Paget’s disorder in bone, osteoporosis and some more general skeleton disorders which lead to periodical changes in bone mass, reported by some authors. However, additional studies are needed to make this hypothesis significant. The study has revealed a few interesting techniques. When studying a multidimensional phenomenon, as a bone tissue is, the visualisation and data reduction is important for analysis and interpretation of results. In the study two novel technical methods have been proposed. The first is the graphical matrix method to visualise/project the multidimensional phase space of variables into diagonal matrix of regular combination of two-dimensional graphs. This significantly simplifies the analysis and, in principle, makes it possible to visualise the phase space higher than three-dimensional. The second important technical development is the application of the Monte-Carlo method in combination with the regression method to study the character and stability of the equilibrium points of a dynamic system. The advantage of this method is that it enables the most influential parameters that affect the character and stability of the equilibrium point to be identified from a large number of the rate parameters/constants of the dynamic system. This makes the interpretation of parameters and conceptual verification of the model much easier.
8
Ljunggren, Östen. "Involvement of bradykinin in inflammation induced bone resorption." Umeå : University of Umeå, 1991. http://catalog.hathitrust.org/api/volumes/oclc/24493228.html.
9
Korhonen, T. (Tommi). "Bone flap survival and resorption after autologous cranioplasty." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526222530.
Анотація:
Abstract This thesis evaluated the factors affecting bone flap survival and bone flap resorption after primary cranial reparation surgery, cranioplasty, conducted to repair a cranial bone defect with an autologous cryopreserved bone flap. Emphasis is put on the predictors, progression, and definition of an important yet poorly understood postoperative complication, bone flap resorption. Study I assessed the rates and predictors of bone flap removal and bone flap resorption in a Finnish retrospective multicentre setting. 40% of patients developed complications of whom half required bone flap removal. Bone flap resorption and surgical site infections were the underlying cause in 90% of bone flap removal surgeries. The prevalence of both surgical site infections and bone flap resorption was 9%. In summary, young age was found to predict bone flap resorption and smoking predisposed patients to infections requiring bone flap removal. Study II applied computed tomography-based volumetry to evaluate the prevalence of subclinical bone flap resorption and to monitor its progression. In the follow-up, 90% of patients were found to have decreased bone flap volumes indicating varying degrees of resorption. However, the progression of bone flap resorption as a function of follow-up time was non-linear on the cohort level, and thus routine radiological follow-up seems unjustified. Most bone flaps do not appear to resorb enough to require removal even in the long-term follow-up. Study III addressed the unclarity in the definition of bone flap resorption. The computed tomography-based Oulu Resorption Score was developed to standardise the interpretation of radiological bone flap resorption and to guide follow-up interventions. The score values range from 0 to 9 with increasing values implying more severe bone flap resorption. Coupled with radiological evaluation conducted by independent neurosurgeons, an Oulu Resorption Score of ≥5 was defined to be clinically relevant. Further, the scores were divided into four grades based on the recommended follow-up procedures. Grades 0 (score 0) and I (scores 1 to 4) require no additional follow-up, but those with a grade II (score 5 to 8) or III (score 9) should be referred to neurosurgical consultation with reoperation considered at least in cases of grade III bone flap resorptionTiivistelmä Tässä väitöstyössä selvitettiin potilaan omalla kylmäsäilytetyllä luuistutteella tehtyjen kallon luupuutosten ensikertaisten korjausleikkausten tuloksiin vaikuttavia tekijöitä. Erityisesti tarkasteltiin luuistutteen liukenemisen, erään tärkeän, joskin heikosti ymmärretyn komplikaation ennustavia tekijöitä, etenemistä ja määritelmää. Tutkimuksessa I selvitettiin luuistutteen poiston ja liukenemisen yleisyyttä ja näihin vaikuttavia tekijöitä suomalaisessa takautuvassa monikeskusaineistossa. Potilaista 40 %:lle kehittyi komplikaatio. Komplikaatioista puolet johti istutteen poistoon. Luuistutteen liukeneminen ja leikkausalueinfektiot muodostivat 90 % poistoon johtaneista komplikaatioista. Sekä infektioiden että istutteen liukenemi¬sen esiintyvyys oli 9 %. Nuori ikä altisti istutteen liukenemiselle ja tupakointi leikkausalueinfektiolle. Tutkimuksessa II sovellettiin tietokonetomografiaan perustuvaa tilavuusmittausta luuistutteen oireettoman liukenemisen esiintyvyyden ja etenemistaipumuksen selvittämiseksi. Seurannassa 90 %:lla potilaista todettiin alentunut luuistutteen tilavuus viitaten asteeltaan vaihtelevaan istutteen liukenemiseen. Koko tutkimusjoukon tasolla istutteiden liukeneminen ei kuitenkaan edennyt lineaarisesti seuranta-ajan funktiona, joten rutiininomainen seuranta kuvantamistutkimuksin ei vaikuta perustellulta. Suurin osa luuistutteista liukeni niin vähän, ettei uutta leikkausta tarvittu pitkässäkään seurannassa. Tutkimuksessa III käsiteltiin luuistutteen liukenemisen nykyisellään epäselvää määritelmää ja kehitettiin uusi tietokonetomografiaan perustuva pisteytysjärjestelmä (Oulu resorption score) tarkoituksena vakioida radiologisten luuistutteen liukenemislöydösten tulkinta ja ohjata hoitolinjan valintaa. Pisteytysarvot vaihtelevat välillä 0-9. Kasvava arvo kuvaa luuistutteen liukenemisen vaikeusasteen kasvua. Luokitus yhdistettiin riippumattomien neurokirurgien radiologisiin arvioihin, joiden perusteella pistemäärä ≥5 määriteltiin kliinisesti merkitykselliseksi. Pistemäärät jaettiin neljään luokkaan suositeltujen jatkotoimenpiteiden mukaisesti. Luokkia 0 (0 pistettä) ja I (1–4 pistettä) vastaava luuistutteen liukeneminen ei vaadi jatkotoimenpiteitä. Luokkia II (5–8 pistettä) ja III (9 pistettä) vastaavasta luuistutteen liukenemisesta suositellaan konsultoitavan neurokirurgia. Uusintaleikkausta suositellaan harkittavan ainakin luokan III tapauksissa
10
Neale, Susan Dorothy. "The role of macrophages in pathological bone resorption /." Title page, table of contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09MSM/09msmn348.pdf.
11
Dreyer, Craig William. "Clast cell activity in a model of aseptic root resorption." Title page, table of contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09phd778.pdf.
12
Wang, Ee Jen Wilson. "The effects of infection-related factors on bone resorption." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365291.
13
Martin, Joanne. "In vitro osteoclast resorption of calcium phosphate bone substitutes." Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.695663.
Анотація:
Resorption of calcium phosphate (CaP) biomaterials is traditionally assessed using an osteoclast (QC) resorption assay where resorption pits formed on the CaP surface are analysed by microscopy techniques and quantified on the basis of pit number, pit area or pit volume. Pit area measurements (20) have become common practice when assessing CaP biomaterial resorption in vitro. Apart from the time consuming nature of pit area analysis techniques it is not a precise indicator of resorption; variations in pit depth are not taken into consideration and it is unsuitable for use on porous materials where visualisation of internal structures is difficult or for use on materials with rough surfaces where determination of individual pits would be difficult. A 3D quantification of bioresorption is available but requires specialised, expensive equipment. An appropriate measure of resorption was required to be more efficient and more cost-effective than the current available in vitro methods, but most importantly, to directly correlate with pit area measurements and have the ability to be used in a broad range of in vitro experiments. An QC resorption assay was developed and optimised through a series of experiments. The established assay was used to assess several outcome measures as potential indicators of resorption in vitro, namely; the correlation of percentage area resorbed in vitro with Ca and P concentration in cell culture medium, QC number and QC activity. A dense substrate free from surface anomalies was used to accurately correlate pit area with the alternative outcome measures. This body of work has established two main outcome measures of bioresorption in vitro that correlate with pit area measurements; Ca and P ion concentration in culture medium and QC specific enzyme activity. These outcome measures will prove invaluable for improving the fundamental understanding of QC resorption of CaP biomaterials.
14
Reddi, Durga. "Interactions of porphyromonas gingivalis with bone marrow cells : implications on mediators of bone resorption." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/3161.
Анотація:
Periodontitis is a multi-factorial disease characterised by the loss of connective tissue and underlying alveolar bone leading to the loss of teeth. Porphyromonas gingivalis (P. gingivalis) is a gram-negative black pigmented anaerobe associated with chronic periodontitis. Porphyromonas gingivalis possesses a range of virulence factors including gingipains, lipopolysaccharide (LPS) and fimbriae. Receptor activator of nuclear factor-κB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) blocks this process by binding to RANKL and acting as a decoy receptor. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the synthesis of prostaglandin E2 (PGE2), a potent inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intra-cellular signaling proteins that control fundamental cellular events, with implications in inflammation and bone metabolism. This thesis aimed to investigate the effect of P. gingivalis on bone marrow stromal cells, primarily on the regulation of molecular mechanisms involved in bone resorption, using gene and protein expression assays, and secondarily on changes in their global transcriptional profile, using microarray technology. It was determined that P. gingivalis upregulated RANKL and downregulated OPG gene and protein expression, resulting in an increased RANKL/OPG expression ratio. These regulations were partly attributed to its LPS and an unidentified synergistic factor. PGE2 was a key mediator in this regulation of RANKL expression. Further to this, P. gingivalis was shown to signal through p38 MAPK, contributing to the PGE2-mediated RANKL induction. The extension of this work using microarray technology demonstrated that in the present experimental system P. gingivalis positively regulates a broad spectrum of genes involved in promoting inflammation and bone destruction. 2 This thesis shows that P. gingivalis can exert its virulence on bone marrow stromal cells. An interplay of bacterial and host factors leads to the activation of molecular mechanisms of bone resorption, which may be implicated in initiating periodontal disease. Moreover, the identified mediators of bone resorption may serve as potential targets for treating P. gingivalis-associated periodontitis.
15
Negus, Charles Hugh. "Three dimensional dynamic hypoelastic remodeling in the proximal femur /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3208622.
16
Hou, Peng. "Matrix metalloproteinases in the osteoclast, with special emphasis on the molecular cloning and the functional role of matrix metalloproteinase-12." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287350.
17
Al-Dehaimi, Abdulwahed. "Evaluation of galactosyl hydroxylysine as a marker of bone resorption." Thesis, University of Sheffield, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364314.
18
Last, Keith Sydney. "Glycosaminoglycans in gingival crevicular fluid in relation to bone resorption." Thesis, University of Liverpool, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317010.
19
Davey, Tamara. "Functional characterisation of a novel osteoclast-derived factor." University of Western Australia. School of Surgery and Pathology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0219.
Анотація:
[Truncated abstract] Intracellular communication between osteoclasts and osteoblasts is imperative to maintain bone integrity. A myriad of molecules are responsible for regulating osteoblast and osteoclast activity. In particular, it is well documented that osteoblast-derived factors are crucial in directly controlling osteoclast formation and function. Since bone formation is coupled to bone resorption, it would be expected that osteoclasts also have some role in regulating the growth and function of osteoblast cells. However, despite extensive research upon osteoclast and osteoblast biology, the mechanisms by which osteoclasts regulate osteoblast growth and function is not well understood. In an attempt to further elucidate the mechanisms by which osteoclasts and osteoblasts communicate, the technique of subtractive hybridisation was used to identify a novel osteoclastderived factor identical to that of mouse Seminal Vesicle Secretion VII (SVS VII). Previous characterisation of the gene in bone demonstrated that SVS VII was abundantly and specifically expressed by mature osteoclasts (Phan, 2004). Additional research hinted that SVS VII acted as a novel osteoclast-derived factor, that by paracrine mechanisms, targeted osteoblast function (Phan, 2004). However, it remained open as to whether the SVS VII molecule did uniquely target the osteoblast, and whether this interaction influenced bone formation in vivo. Therefore, this thesis endeavoured to functionally characterise the role of the SVS VII molecule in the bone environment. ... Further work is needed to identigy a clear consensus binding sequence, to determine the specificity of the interaction between SVS VII protein and each phage clone, and to isolate a specific binding partner for SVS VII. In conclusion, the studies of this thesis sought to characterise the significance of SVS VII expression by mature osteoclasts, relative to its effects on osteoblast behaviour, but failed to conclusively determine a role for SVS VII in bone. Given that the effects of SVS VII on in vitro osteoblast activity and function are minimal, it is doubtful that SVS VII primarily acts as a paracrine factor integral to osteoblast function. Therefore, these findings conflict with those presented previously (Phan, 2004). However, it was demonstrated that SVS VII treatment was associated with in vivo effect on the skeleton, suggesting that SVS VII may target other elements of the bone microenvironment. Via mechanisms not yet understood, which possibly involves additional factors of the bone 11 extracellular matrix, SVS VII may target a subset of osteoprogenitor cells within the bone environment and act to regulate their proliferation. Therefore, SVS VII may enhance osteogenic precursor cell number at sites of bone formation which would increase the pool of cells that can differentiate down the osteoblast linage and contribute to bone formation. In this regard, SVS VII might function in a manner homologous to the Ly-6 molecule Sca-1 and act as an important factor that maintains a balance between the bone formation and resorption process. Clearly, more work focusing on alternative facets of bone biology is needed to identify whether there is a significant role for SVS VII in skeletal tissue.
20
Lean, Jennifer Maree. "Mechanical stimulation of bone formation in the rat." Thesis, St George's, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263682.
21
Stewart, Charlotte. "Structure activity relationships of bisphosphonate analogues." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=128207.
Анотація:
The nitrogen-containing bisphosphonates (NBPs) are the most widely used treatment for diseases involving excessive osteoclastic bone resorption, such as osteoporosis. The clinical efficacy of NBPs is due in large part to their affinity for bone mineral, but it has been suggested that lowering affinity may have benefits due to altered distribution and duration of action possibly allowing direct anti-tumour effects. In addition, the phosphonocarboxylate (PC) analogues inhibit prenylation more selectively through a different enzyme target, Rab geranylgeranyl transferase (RGGT), which may offer additional benefits by reducing side-effects associated with farnesyl diphosphate synthase (FPPS) inhibition. Using fluorescent analogues of PCs and NBPs demonstrated that mineral affinity not only affects initial bone-binding, but also influences desorption, reattachment and penetration at the bone surface, suggesting that lower affinity compounds have lower retention and increased access to other cell types, such as tumour cells. The work presented aimed to investigate the potential of low affinity analogues by characterising their intracellular potency for inhibiting their target enzymes. The results showed that modification to the phosphonate groups to produce phosphonoalkylphosphinate analogues reduced potency for inhibiting FPPS. By contrast, removal of one of the phosphonate groups to give a monophosphonate changed the target enzyme to RGGT. Modifications to the R1 side-chain (substituting with hydrogen or a halogen) of both NBPs and PCs were studied and showed contrasting results, modifications to the R1 side-chain of NBPs affect their ability to inhibit FPPS whereas the same modification to PCs is insignificant for inhibiting RGGT. This showed the distinction between the structural requirements for inhibition of RGGT and FPPS and furthers the understanding of the structure-activity relationships of both NBPs and PCs which could guide future drug design. Within this thesis the most potent inhibitor of RGGT to date, 3-IPEHPC, was characterised which in addition to having therapeutic potential may be used as tool to investigate the importance of Rab prenylation for cellular function.
22
Frith, Julie C. "Studies into the mechanism of action of clodronate." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299577.
23
Nagao, Jiro. "Computer-Aided Diagnosis of Alveolar Bone Resorption using Dental 3DCT Images." INTELLIGENT MEDIA INTEGRATION NAGOYA UNIVERSITY / COE, 2005. http://hdl.handle.net/2237/10393.
24
Mansfield, Ian David. "The synthesis of novel agents which inhibit tumour-stimulated bone resorption." Thesis, Loughborough University, 1999. https://dspace.lboro.ac.uk/2134/27412.
Анотація:
A range of conjugates which focused on bisphosphonates as delivery molecules and on oestrogens as resorption inhibitors were synthesised. Various moieties were coupled through an ester linkage to bisphosphonates which were then converted to the corresponding bisphosphonic acids. This ester linkage was considered to be readily hydrolysable under normal physiological conditions.
25
Morgan, Hayley Michaela. "Mechanisms involved in breast tumour cell mediated bone resorption in vitro." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393664.
26
Ren, Zhongyuan. "Small molecules regulated bone resorption and enzyme activity in osseous cells." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10291/document.
Анотація:
La Cathepsine K est parmi la plus efficace des collagénases de mammifère pour cliver la triple hélice de collagène de type-1. Nous avons développé une série d'azanitriles, (CKI-8 and CKI-13) inhibiteurs de cathepsine K. CKI-8 (un isomère de CKI-13) et CKI-13 ne sont pas toxiques sur les osteoblastes Saos-2 et les cellules RAW 264.7 jusqu' à une concentration de 1000 nM, tandis qu'ils ne le sont pas jusqu'à une concentration de 100 nM sur les osteoclastes. CKI-8 n'affecte pas l'activité de la phosphatase alkaline ainsi que la minéralisation induite par les Saos-2 et par les osteoblastes primaires. CKI-13 diminue de 35 % la minéralisation induite par les Saos-2 tandis qu'il n'affecte pas la minéralisation induite par les osteoblastes primaires. L'addition de CKI-13 diminue l'activité de la phosphatase alkaline d'environ 20% (Saos-2) et de 40 % (osteoblastes primaires). La résorption osseuse sur des tranches d'os d'origine bovine est diminuée avec 10 nM de CKI-13, 100 nM de CKI- 8 et 100 nM d'inhibiteur commercial E64. CKI-8 et CKI-13 diminuent la mobilité des osteoclastes. Nous avons développé un dosage d'hydrolyse de PPi par la phosphatase alkaline au moyen de l'IR, ayant l'avantage de fonctionner sur des vésicules matricielles et des cellules avec des substrats naturels à un pH physiologique. La bande de PPi localisée à 1107 cm-1 (∑= 2158 ± 211 M-1.cm-1) et celles de Pi localisées à 1076 cm-1 (∑= 1346 ± 116 M-1.cm- 1) et à 991 cm-1 (∑= 493 ± 49 M-1.cm-1) ont servis à mesurer les concentrations du substrat et du produitCathepsin K is among the most potent mammalian collagenase, capable of cleaving the triple helix in type-I collagen. We developed a series of azanitriles (CKI-8 and CKI-13) which are inhibitors of cathepsin K. CKI-8 (an isomer of CKI-13) and CKI-13 did not induce significant toxicity on osteoblasts Saos-2 and RAW 264.7 cells up to 1000 nM, while they were not toxic on mature osteoclasts up to 100 nM. Commercial E64 inhibitor was not toxic in primary osteoclast cells up to 1000 nM. CKI-8 did not affect alkaline phosphatase activity as well the mineralization induced by Saos-2 cells and by primary osteoblasts. CKI-13 decreased by 35% the mineralization induced by Saos-2 cells while it did not on mineralization induced by primary osteoblasts. Addition of CKI-13 decreased alkaline phosphatase activity by around 20% (Saos-2 cells) and 45% (primary osteoblasts). Bone resorption on bovine slices decreased significantly with 10 nM of CKI-13, with 100 nM of CKI-8 and commercial inhibitor E64. Our findings indicated that CKI-8 and CKI-13 inhibited bone resorption and affected the mobility of osteoclast. To monitor directly the PPi hydrolytic activity by alkaline phosphatase, we developed an infrared (IR) assay taking the advantage to use natural substrate under physiological pH in matrix vesicles and in living cells. PPi band located at 1107 cm-1 (∑= 2158 ± 211 M-1.cm-1) and Pi bands located at 1076 cm-1 (∑= 1346 ± 116 M-1.cm-1) and at 991 cm-1 (∑= 493 ± 49 M-1.cm-1) served to measure the substrate and the product concentrations
27
Miao, Dengshun. "Studies on the actions of bone anabolic drugs in vivo and in vitro." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300362.
28
Cvijic, Gojko 1971. "Avaliação radiográfica do nível ósseo em implantes com diferentes tratamentos de superfície, inseridos na área enxertada." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289068.
Анотація:
Orientador: Frederico Andrade e SilvaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
Made available in DSpace on 2018-08-22T06:55:09Z (GMT). No. of bitstreams: 1 Cvijic_Gojko_D.pdf: 2099298 bytes, checksum: abafee052c159ac120d8c1fc520d05e2 (MD5) Previous issue date: 2013
Resumo: O objetivo deste estudo foi comparar o nível de reabsorção óssea em implantes com superfícies física e quimicamente tratadas, carregados com coroas unitárias, inseridos em osso previamente enxertado. Foram avaliadas as imagens digitalizadas das radiografias periapicais de 20 implantes, sendo 10 com superfícies SLA® e 10 com superfícies SLActive® (Instituto Straumann®, Basel, Suíça). Coroas metalocerâmicas foram instaladas doze semanas após a colocação dos implantes no primeiro grupo (SLA) e seis semanas no segundo (SLActive). Radiografias periapicais foram realizadas imediatamente após a colocação das coroas (T0), e aos 3 (T1), 6 (T2) e 12 (T3) meses. Após a digitalização das radiografias, foi medido o Nível Médio de Reabsorção Óssea (NMRO) nos quatro períodos experimentais. Os resultados foram submetidos ao teste ANOVA e Dunnett revelando que o NMRO no grupo SLA variou entre 0,08mm±0,64 (T0) a 0,44mm±0,66 (T3). No grupo SLActive foi de -0,05mm±0,60 (T0) a -0,05mm± 0,41 (T3). A alteração do NMRO não teve valor significativo dentro de cada grupo, porém quando os resultados entre os grupos foram comparados, houve diferença estatística: 0,20mm±0,70 (SLA) e -0,04mm±0,44 (SLActive), (p<0,05). De acordo com metodologia empregada, NMRO no grupo SLActive não reduziu em função da carga mastigatória durante doze meses de avaliação
Abstract: The aim of this study was to compare the level of bone resorption on implants with physically and chemically treated surfaces, placed in grafted maxillae, and loaded with single crowns. The periapical radiographs of twenty implants, 10 with SLA® and 10 with SLActive® surface (Institut Straumann®, Basel, Switzerland), were digitalized and analyzed. The metaloceramic crowns were installed twelve weeks after placing the SLA implants and 6 weeks after SLActive implants. The periapical radiographs were done immediately after crown installing (T0), 3 (T1), 6 (T2) and 12 (T3) months, afterward. The digitalized images were used to analyze the Medium Level of Bone Resorption (MLBR) in four experimental periods (T0, T1, T2, T3). Using ANOVA and Dunnett tests, the results showed that MLBR varied between 0,08 mm ± 0,64 (T0) to 0,44 mm ± 0,66 (T3) in SLA group. Nevertheless, in SLActive group MLBR measured -0,05 mm ± 0,60 (T0) to -0,05 mm ± 0,41 (T3). The MLBR wasn't significant, however, comparing two groups the difference was significant: 0,20 mm ± 0,70 (SLA) and -0,04 mm ± 0,44 (SLActive) (p<0,05). According to used methodology, MLBR around SLActive implants did not reduce after loading, during the twelve months of evaluation
Doutorado
Protese Dental
Doutor em Clínica Odontológica
29
Li, Jian. "Spontaneous correction of fracture deformity : a study in the rat /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-119-9/.
30
Nordahl, Joakim. "Matrix resorption in endochondral bone growth : ultrastructural studies, with special attention to the chondroclast /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4513-6/.
31
Persson, Emma. "The Neuropeptide VIP and the IL-6 family of cytokines in bone : effects on bone resorption, cytokine expression and receptor signalling in osteoblasts and bone marrow stromal cells /." Doctoral thesis, Umeå : Umeå University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-606.
32
Weekes, David Michael. "Lanthanum complexes as therapeutic agents for the treatment of bone resorption disorders." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/58567.
Анотація:
Lanthanum naturally targets and binds skeletal tissue in living systems, wherein it has the potential to treat bone resorption disorders by invoking a biological response that counteracts an imbalanced bone remodeling cycle. Because lanthanum is very poorly absorbed, the key to realizing this potential is through rational chelator design, and in this regard, a number of lanthanum complexes have been designed, synthesized, and tested in an effort to develop an orally-active drug. Previously, past group members Dr. Cheri Barta and Dr. Yasmin Mawani had identified tris-(1,2-dimetyl-3-oxypyridin-4-one) lanthanum(III) (La(dpp)₃) and bis-[[bis(carboxymethyl)amino] methyl]phosphinate lanthanum(III) (La(XT)) as lead drug candidates, and – after tailoring the synthetic procedures to access large quantities of each – these compounds were tested for their thermodynamic and kinetic interactions with synthetic hydroxyapatite (HAP) by isothermal titration calorimetry (ITC) and solution depletion studies, respectively. The systems were also tested for the first time in vivo (healthy Sprague Dawley rats) by measuring lanthanum biodistribution from single-dose intravenous (IV), acute IV, and short-term IV and oral administration of either compound. Overall, it was found that La(XT) was a more viable candidate than La(dpp)₃, primarily due to higher thermodynamic stability which led to better oral uptake. Four new compounds (H₂dpa, H₃cedpa, H₄pedpa, and H₇alenpa) and three of their lanthanum complexes (all but H₇alenpa) were also synthesized, and tested for ligand binding kinetics with HAP (solution depletion studies), thermodynamic stability of the lanthanum complexes (potentiometric and NMR titrations), and lipophilicity of both the ligands and the metal complexes (partition coefficient measurements). It was found that [La(pedpa)]- exhibited the most favourable overall profile for a potential drug candidate, but requires further testing before in vivo trials. Crystal structures for [La₄(pedpa)₄(H₂O)₂] and [La(dpp)₃(H₂O)₂]·11.75H₂O were also obtained.Science, Faculty of
Chemistry, Department of
Graduate
33
Dossa, Tanya. "Osteoclast-specific inactivation of the Integrin-Linked Kinase (ILK) inhibits bone resorption." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=99336.
Анотація:
Bone resorption requires the adhesion of osteoclasts to extracellular matrix (ECM) components, a process mediated by the alphavbeta 3 integrin. Following engagement with the ECM, integrin receptors signal via multiple downstream effectors, including the Integrin-Linked Kinase (ILK). In order to characterize the physiological role of ILK in bone resorption, we generated mice with an osteoclast-specific ILK gene ablation. Mice with one inactivated ILK allele (ILK+/-) were mated with TRAP-Cre transgenic mice. Progeny from this cross (TRAP-Cre;ILK+/-) was bred to mice homozygous for a floxed ILK allele (ILKfl/fl) to yield mutant mice with ILK-deficient osteoclasts (TRAP-Cre;ILK+/fl ). The mutant animals thus had one ILK allele inactivated in all tissues, and both alleles disrupted in osteoclasts. Mutant mice appeared phenotypically normal, but histomorphometric analysis of the proximal tibia revealed an increase in bone volume and trabecular thickness. Osteoclastogenesis, assessed by TRAP staining of bone sections or in vitro cultures, was not affected. Indeed, osteoclast-specific ILK ablation was associated with an increase in osteoclast number both in vitro and in vivo. Primary cultures of osteoclasts were generated on synthetic calcium phosphate discs, as well as dentin, and the mutant cells displayed a decrease in resorption activity. We also measured decreased serum concentrations of the C-terminal telopeptide of collagen, a marker of osteoclastic activity, in mice with ILK-deficient osteoclasts. Our results show that ILK is important for the function, but not the differentiation, of osteoclasts. The characterization of the molecular mechanisms responsible for the observed phenotype will identify novel pathways regulating bone resorption.
34
Althnaian, Thnaian Ali. "Factors that regulate osteoclast formation and bone resorption in regenerating deer antlers." Thesis, Royal Veterinary College (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439832.
35
Tkachenko, Evgeniy. "Measures of Individual Resorption Cavities in Three-Dimensional Images in Cancellous Bone." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301413780.
36
Yung, Koon-yu Samuel. "Effects of green tea on bone loss in mature ovariectomized rat." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23339846.
37
Chaplais, Elodie. "The Adibox Study: Adiposity and Bone Metabolism: Effects of Exercise-induced Weight Loss in Adolescents with Obesity." Thesis, Australian Catholic University, 2017. https://acuresearchbank.acu.edu.au/download/53f5d8a6c9f7442b4ab4a69db7896bd9e81a4d0daa6c4ceb4223556dcd7524e6/27301614/CHAPLAIS_2017_THESIS.pdf.
Анотація:
Introduction: This program of research targeted the impact of an 8-month weight loss intervention induced by physical activity and nutrition on bone health in adolescents with obesity. The overall aim of this thesis was to examine the impact of a lifestyle weight loss intervention on the bone parameters in adolescents with obesity.
Method: Sixty-five adolescents were recruited: 31 (6 males) adolescents with obesity in the weight loss intervention (age: 13.61 (1.27)), 23 normal weight (NW) adolescents (age: 15.90 (0.43)) and 11 (4 males) adolescents with obesity in another control group (14.02 (1.39)). Primary outcomes targeted bone densitometry (whole body, spine, hip DXA). Secondary outcomes included body composition, bone geometry and strength (hip structural analysis) and bone biomarkers (procollagen type 1 N-terminal propeptide (P1NP), C telopeptide (CTx) estradiol, leptin). Data were collected at baseline, 4 months and 8 months. Data were adjusted for body weight, fat mass and lean mass changes.
Results: Compared with the NW controls, adolescents with obesity displayed lower unadjusted and adjusted bone density. Following successful weight loss (~ -11%) adolescents with obesity increased whole body (%Ob Δ 3.22 (3.58) pp<0.001) and lumbar spine (%Ob Δ 6.27 (12.45) p=0.014) BMD. However, values remain lower than their NW peers after adjustment to body weight changes. After the weight loss intervention, compromised estimates of fracture risk remained especially at the narrow neck (buckling ratio (BR) 8.25 (2.00) p=0.005), despite positive adaptations of some geometric properties (i.e. NN CSA, NN Z). Also, bone accretion changes in adolescents with obesity followed an androgen-like adaptation demonstrated by periosteal expansion (% NW Δ 0.69 (3.71); Ob Δ 1.67 (9.11)) and endocortical resorption (% NW Δ -2.11 (11.79); Ob Δ 4.42 (10.56)). Among the intervention group, differences in bone markers favoured formation during the first 4 months and favoured resorption in the remaining months.
Conclusion: Bone fragility in adolescents with obesity was demonstrated by (1) baseline and post intervention lower whole body and regional BMD than NW controls, (2) post-intervention higher fracture risk index at the narrow neck, (3) bone biomarkers showing reduced z-scores, uncoupling indices and qualitative representations of the distribution of bone remodeling. Future investigations of links between bone and obesity during adolescence can be well informed by the results of this thesis.
38
Martin, Chelsea Kathleen. "Mechanisms and Treatment of Bone Resorption in Models of Oral Squamous Cell Carcinoma." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1285015046.
39
Howie, Donald William. "The role of wear particles in prosthesis loosening /." Title page, contents and summary only, 1987. http://web4.library.adelaide.edu.au/theses/09PH/09phh861.pdf.
40
Davies, Emma Louise. "Heat shock proteins : interactions with bone and immune cells." Thesis, University of Chester, 2004. http://hdl.handle.net/10034/76182.
Анотація:
Heat shock proteins (Hsps) are increasingly being seen as having roles other than those of intracellular molecular chaperones, particularly with regard to their potential to act as cytokines, and to stimulate the innate immune system. Hsps have also been found to promote bone resorption and osteoclast formation in vitro, although the mechanism has not been previously identified. The overall aims of this thesis were to determine whether Hsps could stimulate bone resorption by affecting the RANKL/OPG pathway, and to address the hypothesis that Hsps can act as a danger signal to the innate immune system. In order for Hsps to affect either the RANKL/OPG system of bone resorption or act as danger signals they would need to be actively released from cells, ideally in a controlled manner following exposure to the source of stress. Hsp60 and Hsp70 were found to be released from a range of immune cells including the cell lines Jurkat and U937, and also PBMCs, T-cells and B-cells. This release was not due to cell damage. The release of Hsp60 and Hsp70 were downregulated by inhibitors of protein secretion, in particular Hsp70 release was reduced by compounds that inhibited lysosomal pathways and Hsp60 release by classical secretion inhibitors. Hsp60, Hsp70, GroEL and LPS all affected the RANKL/OPG system of bone regulation; OPG production and release was down-regulated in the MG63 and GCT osteoblast-like cell lines following treatment with Hsp60, Hsp70 and LPS, and RANKL expression was upregulated following treatment with Hsp60, Hsp70, GroEL and LPS. This effect on the RANKL/OPG system was found to translate into an effect on osteoclast formation when conditioned media from treated osteoblasts was added to osteoclast precursors in the presence of M-CSF. A range of different factors that affected Hsp release were identified; PHA activation of PBMCs was found to upregulate Hsp60 release from PBMCs. GroEL and LPS caused an upregulation in Hsp70 release from PBMCs and GCT osteoblast like cells, and Hsp70 was found to stimulate Hsp60 release from PBMCs and GCT cells. These responses of Hsp release were used to form a theory of a cascade-like danger signal that may occur when cells are exposed to bacterial infection and which would result in activation of antigen presenting cells via previously identified receptors for Hsps such as CD14/TLR4 or by unidentified pathways. The elevated release of Hsps in response to GroEL and LPS was also identified as a mechanism that could stimulate bone loss during infection or autoimmuniry by affecting the RANKL/OPG system. hi conclusion, Hsp60 and Hsp70 can be released from immune cells under normal conditions, and from both immune and osteoblast-like cells following stimulation with LPS and other Hsps. The observed release responses provide a mechanism through which Hsps can act as danger signals to the innate immune system, and also as promoters of bone resorption via the RANKL/OPG system.
41
Peng, Songlin, and 彭松林. "Investigation of the cellular and molecular mechanisms for the dual effect of strontium on bone." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45585167.
42
Mattila, P. (Pauli). "Dietary xylitol in the prevention of experimental osteoporosis:beneficial effects on bone resorption, structure and biomechanics." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:951425158X.
Анотація:
Abstract
Dietary xylitol supplementation increases bone calcium and
phosphorus concentrations in healthy rats, as well as protects
against the decrease of bone minerals and bone density during experimental
osteoporosis. This suggests that dietary xylitol might have a favorable
effect on the prevention of osteoporosis. However, before any conclusions
can be drawn about the usefulness of a compound, studies including
structural evaluation and biomechanical testing of bones must first
be performed.
Thus, the aim of the present study was to clarify whether
dietary xylitol affects bone resorption, bone structure, and bone
biomechanics in healthy rats, and whether dietary xylitol offers
some preventive effects against the increased bone resorption,
decreased bone trabeculation, and weakened bone biomechanical properties
during experimental osteoporosis.
Dietary xylitol reduced bone resorption in 3-mo old healthy
male rats, and protected significantly against the increase of
bone resorption in 3-mo old ovariectomized rats, as measured by
the urinary excretion of 3H following [3H]tetracycline-prelabeling.
In addition, increased trabecular bone volume of proximal tibia
in 4-mo old healthy male rats was detected after a 1-mo xylitol
feeding period, and significant protection against the decrease
of trabecular bone volume in 6-mo old ovariectomized rats was observed
after a 3-mo xylitol feeding period. Furthermore, dietary xylitol
increased the strength properties of long bones in 6-mo old healthy
male rats after a 3-mo feeding period, without affecting the bone
elastic properties as tested by three-point bending of tibia, torsion
of femur, and loading of femoral neck. Accordingly, dietary xylitol
protected significantly against the weakening of bone biomechanical
properties in 6-mo old ovariectomized rats after a 3-mo feeding
period.
In conclusion, the above results strongly support the hypothesis
that oral administration of xylitol protects effectively against
the progression of experimental osteoporosis. Dietary xylitol was
effective both in increasing bone mass in healthy rats, and in
preventing bone loss in ovariectomized rats, suggesting a favorable
effect of xylitol on both main targets in the prevention of osteoporosis.
As dietary xylitol was effective also in protecting against the
experimental osteoporosis-caused changes in bone structure and
weakening of bone biomechanical properties, oral xylitol administration
seems to provide interesting possibilities when searching for new
physiological choices for the prevention of osteoporosis.
43
Symons, Anne L. "The dento-alveolar complex /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17714.pdf.
44
Crawford, Ross William. "Focal femoral osteolysis in cemented total hip replacement." Thesis, University of Oxford, 2000. http://ora.ox.ac.uk/objects/uuid:67914dbd-6405-41a3-b4d6-6baeb8bbf0bf.
Анотація:
As implant survival extends into the second and third decades focal osteolysis around cemented femoral components in total hip replacement is emerging as an important failure mechanism. Whilst the problem of focal osteolysis is well recognised, there are many aspects of its development which are poorly understood. The broad aim of this thesis is to try to provide some insights into how, why and where focal osteolysis develops around the cemented femoral component. There are broadly two sections to this thesis, chapters 2-5 present clinical and geometrical studies and chapters 6-10 a series of experimental studies. The aim of the first section was to establish what is observed in clinical practice, the aim of the second to try to explain these findings. A mid-term clinical study showed that focal osteolysis is more common with rough than polished stems that differed in no aspect other than their surface finish. Further studies established that focal osteolysis is probably always associated with defects in the cement mantle. These defects occur anteriorly at the mid-stem of the prosthesis and posteriorly at the component tip. The distribution of focal osteolysis and its strong association with cement mantle defects suggests the importance of the stemcement interface as a pathway for fluid and debris to reach the distal femur. However, at 15-25 years, osteolysis rarely develops with the polished Exeter stem even in the presence of confirmed defects in the cement mantle, suggesting that the stem seals the stem-cement interface against fluid and debris. In an attempt to explain the clinical findings a series of bench top experiments were undertaken. These studies showed that the behaviour of fluid and dye at the stemcement interface was significantly influenced by component surface finish. Bonded and debonded stem-cement interfaces of rough stems provided an incomplete barrier to fluid movement along this interface. In contrast, polished stems both bonded and debonded were able to provide a seal at the stem-cement interface. The seal at this interface was improved with component subsidence in the presence of rotational stability. It is believed that this thesis provides a rationale explanation for why focal osteolysis rarely develops around the Exeter stem in clinical practice. It also explains how, where, and why osteolysis develops around certain designs of cemented femoral components used in total hip replacement.
45
Willey, Jeffrey S. "Radiation-induced osteoporosis bone quantity, architecture, and increased resorption following exposure to ionizing radiation /." Connect to this title online, 2008. http://etd.lib.clemson.edu/documents/1211387053/.
46
Maeda, Miki [Verfasser], and Eric [Akademischer Betreuer] Hesse. "Role of Tgif1 in osteoclast differentiation and bone resorption / Miki Maeda ; Betreuer: Eric Hesse." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1183262426/34.
47
Antonioli, Corboz Véronique. "Effect of macrophage colony-stimulating factor on "in vitro" osteoclast generation and bone resorption /." Bern, 1993. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
48
Egger, Chantal Denise. "Evaluation of urinary pyridinoline excretion as a marker of bone resorption in the rat /." Bern : [s.n.], 1993. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
49
Frota, Nicolly Parente Ribeiro. "Effects of Tiludronate Administration as an Adjunctive to Mechanical Periodontal Treatment or not in Experimental Periodontitis in Rats." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10150.
Анотація:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorBackground and Objectives: The proven efficacy of bisphosphonates to inhibit the osteoclastic bone resorption has led to their use in the management of periodontal diseases. This dissertation, comprised by 2 manuscripts, aimed: (1) to histologically analyze the effects of systemic administration of Tiludronate (TIL) on ligature-induced periodontitis in rats; (2) to histologically analyze the effects of systemic administration of TIL as an adjunctive therapy to mechanical periodontal treatment on ligature-induced periodontitis in rats. Methods: In study 1, 32 adult male rats were divided into four groups (n=8): C, PD, PD-TIL5, PD-TIL15 (CâControl group, PDâPeriodontitis groups). On PD groups, a ligature was placed in the cervical area of the right mandibular 1st molar of each rat. After 15 days, TIL solutions (TildrenÂ, Ceva SaÃde Animal Ltda., PaulÃnia, SP, Brazil) at dosages of 5 mg/kg body weight (group PD-TIL5) or 15 mg/kg body weight (group PD-TIL15) were subcutaneously administered 5 times a week for 3 weeks. In study 2, 40 adult male rats were divided into five groups (n=8): C, PD, PDT, PDT-TIL 5, PDT-TIL 15. On PD groups, ligatures were placed as described. After 15 days, ligatures of the rats from groups PDT, PDT-TIL5 and PDT-TIL15 were removed and scaling and root planing were performed. TIL solutions at dosages of 5 mg/kg body weight (group PDT-TIL5) or 15 mg/kg body weight (group PDT-TIL15) were subcutaneously administered 5 times a week for 3 weeks. All animals were euthanized at the 36th day. Histometric and histologic analyses were performed. Data were statistically analyzed (ANOVA, Tukey, p<0.05). Results: In study 1, alveolar bone loss was significantly reduced in group PD-TIL5 (1.12 mmÂ0.24), when compared with groups PD (1.70 mmÂ0.32) and PD-TIL15 (1.47 mmÂ0.21). The animals from all PD groups presented more periodontal attachment loss than the ones from group C (0.12 mmÂ0.09). There were no differences in periodontal attachment loss among PD groups (PD: 0.53 mmÂ0.19; PD-TIL5: 0.37 mmÂ0.09; PD-TIL15: 0.52 mmÂ0.13). In study 2, there were no differences in alveolar bone losses among groups PDT (1.27 mmÂ0.15), PDT-TIL 5 (1.18 mmÂ0.10) and PDT-TIL 15 (1.26 mmÂ0.40). The alveolar bone losses found in these groups were slighter than the alveolar bone loss observed in group PD and did not statistically differ from the alveolar bone loss found in group C. Animals from all groups with periodontitis induction (group PD: 0.59 mmÂ0.16; group PDT: 0.39 mmÂ0.07; group PDT-TIL 5: 0.42 mmÂ0.05; group PDT-TIL 15: 0.48 mm  0.09) presented periodontal attachment losses statistically greater than the animals from group C (0.12 mmÂ0.09). Groups PDT and PDT-TIL 5 presented less periodontal attachment loss than group PD. Conclusions: Within the limits of this study, it can be concluded that (i) systemically-administered TIL solution reduced alveolar bone loss in established periodontitis in rats, (ii) dosage of TIL may influence its anti-inflammatory and anti-resorptive properties and (iii) systemically-administered TIL did not result in additional benefits to periodontal mechanical therapy in rats with experimental periodontitis.
IntroduÃÃo e Objetivos: A eficÃcia comprovada dos bisfosfonatos em inibir a reabsorÃÃo Ãssea osteoclÃstica levou à utilizaÃÃo dos mesmos no tratamento da periodontite. Esta dissertaÃÃo, composta por 2 artigos, teve como objetivos: (1) avaliar, histologicamente, os efeitos da administraÃÃo sistÃmica do bisfosfonato Tiludronato (TIL) na periodontite induzida por ligadura em ratos; (2) avaliar, histologicamente, os efeitos da administraÃÃo sistÃmica do TIL como terapia adjuvante ao tratamento periodontal mecÃnico na periodontite induzida por ligadura em ratos. MÃtodos: No estudo 1, 32 ratos adultos machos foram divididos em 4 grupos (n=8): C, DP, DP-TIL5 e DP-TIL15 (C-grupo Controle, DP-grupos Periodontite). Nos grupos DP, ligaduras foram colocadas na Ãrea cervical dos 1os molares inferiores direitos de cada um dos ratos no 1 dia. ApÃs 15 dias, soluÃÃes de TIL (TildrenÂ, Ceva SaÃde Animal Ltda., PaulÃnia/SP, Brasil) nas dosagens de 5 mg/kg de peso corporal (grupo DP-TIL5) e 15 mg/kg de peso corporal (grupo DP-TIL15) foram administradas, 5 vezes por semana, durante 3 semanas. No estudo 2, 40 ratos adultos machos foram divididos em 5 grupos (n=8): C, DP, DPT, DPT-TIL5 e DPT-TIL15. Nos grupos DP, foram colocadas ligaduras, conforme descriÃÃo anterior. ApÃs 15 dias, as ligaduras dos ratos dos grupos DPT, DPT-TIL5 e DPT-TIL15 foram removidas, e foram realizados raspagem e alisamento radicular. SoluÃÃes de TIL nas dosagens de 5 mg/kg de peso corporal (DPT-TIL5) e 15 mg/kg de peso corporal (DPT-TIL15) foram administradas, 5 vezes por semana, durante 3 semanas. Os animais foram submetidos à eutanÃsia no 36 dia. Foram realizadas anÃlises histolÃgica qualitativa e histomÃtrica. Os dados obtidos foram analisados estatisticamente (ANOVA, Tukey, p< 0,05). Resultados: No estudo 1, a perda Ãssea alveolar foi significativamente reduzida no grupo DP-TIL5 (1,12 mmÂ0,24), quando comparada à dos grupos DP (1,70 mmÂ0,32) e DP-TIL15 (1,47 mmÂ0,21). Os animais dos grupos DP apresentaram maior perda de inserÃÃo quando comparados aos do grupo C (0,12 mmÂ0,09). NÃo houve diferenÃas na perda de inserÃÃo entre os grupos DP (DP: 0,53 mmÂ0,19; DP-TIL5: 0,37 mmÂ0,09; DP-TIL15: 0,52 mmÂ0,13). No estudo 2, nÃo houve diferenÃas na perda Ãssea alveolar entre os grupos DPT (1,27 mmÂ0,15), DPT-TIL 5 (1,18 mmÂ0,10) e DPT-TIL 15 (1,26 mmÂ0,40). A perda Ãssea alveolar observada nesses grupos foi menor que a do grupo DP e nÃo diferiu estatisticamente da perda Ãssea alveolar encontrada no grupo C. Todos os animais dos grupos com ligadura (grupo DP: 0,59 mmÂ0,16; grupo DPT: 0,39 mmÂ0,07; grupo DPT-TIL 5: 0,42 mmÂ0,05; grupo DPT-TIL 15: 0,48 mm  0,09) apresentaram perdas de inserÃÃo estatisticamente maiores que os animais do grupo C (0,12 mmÂ0,09). Os grupos DPT e DPT-TIL 5 apresentaram menor perda de inserÃÃo que o grupo DP. ConclusÃes: Dentro dos limites deste estudo, pode ser concluÃdo que (i) a administraÃÃo sistÃmica de TIL reduziu a perda Ãssea alveolar na periodontite estabelecida em ratos; (ii) a dosagem do TIL pode influenciar suas propriedades antirreabsortivas e anti-inflamatÃrias; (iii) a administraÃÃo sistÃmica de TIL nÃo proporcionou benefÃcios adicionais à terapia periodontal mecÃnica em ratos com periodontite experimental.
50
Cheng, Tak Sum. "Molecular identification and characterization of novel osteoclast V-ATPase subunits." University of Western Australia. School of Surgery and Pathology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0068.
Анотація:
[Truncated abstract] Osteoclasts are multinucleated giant cells responsible for the resorption of the mineralized bone matrix during the process of bone remodelling. During activation towards bone resorption, polarization of the osteoclast results in the formation of a unique plasma membrane, the ruffled border, the actual resorptive organelle of the osteoclast. Through this domain protons are actively pumped into the resorption lacuna creating an acidic microenvironment that favours the dissolution of the mineralized bone matrix. The polarised secretion of protons is carried out by the action of the vacuolar-type (H+)-ATPase (V-ATPase), composed of functionally and structurally distinct subunits of the V1 and V0 domains. The general structure of the V-ATPase complex is highly conserved from yeast to mammals, however, multiple isoforms for specific V-ATPase subunits do exist exhibiting differential subcellular, cellular and tissue-specific localizations. This study focuses on the molecular identification and characterization of V-ATPase accessory subunit Ac45 and the d2 isoform of the V0 domain d subunit in osteoclasts. Using the techniques of cDNA Subtractive Hybridization and DNA Micro-Array analyses respectively, the accessory subunit Ac45 and the d2 isoform of the V0 domain d subunit were identified in RAW264.7-cells derived OcLs. ... Using web-based computational predictions, two possible transmembrane domains, an N-terminus 'signal anchor' sequence and a C-terminus dilysine- like endoplasmic reticulum (ER) retention signal were identified. By confocal microscopy, EYFP-tagged e was found to localize to the perinuclear region of transfected COS-7 cells in compartments representing the ER and Golgi apparatus with some localization in late endosomal/lysosomal-like vesicles. ER truncation of e did not alter its subcellular localization but exhibited significantly weaker association with Ac45 compared to the wild-type as depicted by BRET analyses. Association with the other V0 subunits remain unaffected. This may hint at a possibility that Ac45 may play a role in the masking of the ER signal of e following it's incorporation into the V0 domain. Although no solid evidence for a role in the assembly of the mammalian VATPase have been established, subunit e still represents a potential candidate whose role in the V-ATPase complex requires further investigation. Collectively, the data presented in this thesis has provided further insight into the composition of the osteoclast V-ATPase proton pump by: 1) identifying an accessory subunit, Ac45 which shows promise as a potential candidate for the regulation and/or targeting of the V-ATPase complex in osteoclasts and truncation of its targeting signal impairs osteoclastic bone resorption; 2) identification and preliminary characterization of the d2 isoform of the V0 domain d subunit whose exact role in the V-ATPase complex and in osteoclasts remains to be determined, although its has been implicated to be essential for osteoclastic function; and 3) Preliminary characterization of subunit-e, a potential assembly factor candidate for the mammalian V-ATPase V0 domain.