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Apfeldorfer, Coralie. "Lysosome biogenesis during osteoclastogenesis". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1164801444532-19433.
Pełny tekst źródłaDay, Christopher. "Genes Involved in Osteoclastogenesis". Thesis, Griffith University, 2005. http://hdl.handle.net/10072/367814.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Full Text
Ansalone, Cecilia. "Myeloid precursors, osteoclastogenesis, and Spondyloarthropathies". Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7578/.
Pełny tekst źródłaWitte, Sara. "The effect of redoxmodulation on osteoclastogenesis". Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-57263.
Pełny tekst źródłaDuring osteoclast differentiation and bone resorption the redox status in the cell display a decrease in reduction and a shift to an oxidized state. Structure, metabolism and function are some of the extensive changes that cells undergo during differentiation which alters both the extra- and intracellular redox environment. Osteoclasts express enzymes such as TRAP and NADPH oxidase which generates reactive oxygen species (ROS). ROS are molecules formed by oxygen reduction which gives these radicals at least one unpaired electron and makes them very reactive and chemically unstable. These are factors which stimulates differentiation of osteoclasts and bone resorption. RAW 264.7 cells will differentiate to osteoclasts when stimulated with RANKL and to activated macrophages when stimulated with LPS.
The aim of this project was to analyze if the redox environment is affected during differentiation of RAW 264.7 cells to osteoclasts and macrophages. The reason for this was that we aimed to se if RAW 264.7 cells could be used as an in vitro system to study the effects of redox changes in osteoclasts and macrophages and their activation.
Results from Western blot showed that protein expression of the Cysteine/Glutamate transporter xCT was up regulated with LPS and downregulated with RANKL. Results from the GSH/Cys assay show that the treatments with redox modulators did not affect the levels of GSH and Cys to a measurable extent. However the levels increased for both intracellular and extracellular GSH and Cys forms at day 4 in the control and stimulated cells. Addition of the disulfide reductant DTT affected differentiation to osteoclasts, leading to smaller osteoclasts probably due to interference with fusion of mononuclear pre-osteoclasts. Thus, down regulation of the xCT transporter could be an important mechanism to maintain a low level of free thiols shown to interfere with the differentiation to osteoclasts.
Agrawal, Ankita. "Regulation of osteoclastogenesis by purinergic signalling". Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/4679/.
Pełny tekst źródłaDoonan, James Joseph. "Fc gamma receptor mediated modulation of osteoclastogenesis". Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5579/.
Pełny tekst źródłaCaballé, Serrano Jordi. "In vitro study of osteoclastogenesis under simulated bone augmentation: The effects of bone-conditioned medium and saliva on osteoclastogenesis". Doctoral thesis, Universitat Internacional de Catalunya, 2015. http://hdl.handle.net/10803/311633.
Pełny tekst źródłaLa present tesis doctoral és un compendi de quatre publicacions ampliant el coneixement de l’osteoclastogènesis en les regeneracions òssies, més especialment sobre els efectes de la saliva i el medi condicionat ossi en l’osteoclastogènesis. La reabsorció dels empelts ossis i de l’os de l’hoste, pot ser un repte especialment quan un defecte ossi ha de ser regenerat en condicions desfavorables o grans atròfies com per exemple després de traumatismes, diverses patologies, edat avançada o extraccions múlti¬ples. En la cavitat oral, la saliva pot entrar en contacte amb superfícies mineralitzades, tot i això la relació entre saliva i reabsorció òssia és encara desconeguda. En la present tesis hem examinat si la saliva afecta el procés de l’osteoclastogènesis in vitro, possiblement afectant a la regeneració i cicatrització òssia. La regeneració òssia és un procés comú en traumatolo¬gia, periodòncia, cirurgia oral i maxil•lofacial que involucra l’ús de substituts ossis. Els empelts d’os autòleg són considerats l’estàndard d’or dels sub¬stituts ossis degut a la seva trinitat de propietats: osteoconductivitat, oste¬oinducció i osteogènesis. Els factors paracrins alliberats pels empelts d’os autòleg podrien contribuir en el conjunt de processos que donen com a re-sultat la consolidació del empelts, tanmateix els mecanismes que regeixen aquest processos no són coneguts. En el present treball hem pogut carac¬teritzar un conjunt de proteïnes alliberades per partícules d’os cortical porcí en el medi condicionat ossi (BCM) per imitar l’ambient paracrí dels em¬pelts d’os cortical. Alguns dels factors alliberats pels empelts d’os autòleg podrien influenciar la reabsorció òssia explicant per què els osteoclasts es formen ràpidament a la superfície de les partícules d’os autòleg en els llocs regenerats. Tot i això els mecanismes moleculars que regeixen aquest pro¬cés, encara son desconeguts. Factors solubles alliberats pels empelts d’os autòleg in vitro tenen un impacte robust a la diferenciació de cèl•lules mes¬enquimals. En la present tesis doctoral, hem determinat si aquests factors solubles son capaços de canviar la diferenciació de cèl•lules mare hemat¬opoètiques a osteoclasts, desconegut abans de realitzar els estudis aquí presentats. Basant-nos en els resultats in vitro aquí presentats, es pot observar que la saliva suprimeix l’osteoclastogènesis i promociona el desenvolupament de cèl•lules amb un fenotip fagocític, afectant a la funció dels osteoclasts, les cèl•lules encarregades de reabsorbir l’os. La reabsorció dels empelts d’os autòleg es pot atribuir a l’efecte d’algunes de les proteïnes detecta¬des en les secrecions dels auto-empelts, anomenant aquestes secrecions Medi Condicionat d’Os (BCM). Un estudi proteòmic del BCM va mostrar que aquest medi condicionat conté més de 150 proteïnes, de les quals 43 es van caracteritzar com “secretades” i presents en la matriu extracel•lular. Vàrem descobrir que alguns dels factors continguts en el BCM com per exemple pleiotropina, galectina-1 o TGF-β1 poden afectar processos cel•lulars involucrats en la regeneració òssia. El resultats presentats en aquesta tesis sobre l’influencia del BCM en l’osteoclastogènesis demostra que el BCM termo-activat és capaç d’estimular l’osteoclastogènesis in vitro. Aquests resultats in vitro suporten la noció que la reabsorció dels auto-empelts ossis pot ser que estigui estimulada per mecanismes reguladors encara no definits. En aquesta línia, els protocols presentats sobre l’ús del BCM haurien d’animar a revelar els efectes paracrins dels empelts d’os autòleg durant el procés de regeneració òssia i obrir nous camins a investi¬gacions translacionals en l’ampli camp de la cirurgia reconstructora. Resumint-ho tot, podem concloure que la saliva afecta la reabsorció òssia promocionant el desenvolupament de cèl•lules amb un fenotip fagocític, i que no només la saliva pot afectar a la reabsorció òssia, sinó que també les se¬crecions dels injerts d’os autòleg. En aquest punt, hi ha suficient evidencia per concloure que els auto-empelts d’os no només tenen tres propietats, sinó una més: la propietat reguladora, la quarta dimensió dels empelts d’os autòleg.
Rashid, A. N. M. Mamun Or. "Modulation of in vitro osteoclastogenesis by glycated proteins". Thesis, https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB13059543/?lang=0, 2017. https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB13059543/?lang=0.
Pełny tekst źródła博士(理学)
Doctor of Philosophy in Science
同志社大学
Doshisha University
Khol, Matthew Philip. "The Effects of Recombinant Osteoactivin on Murine Osteoclastogenesis". NEOMED Integrated Pharmaceutical Medicine / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1424053380.
Pełny tekst źródłaBendixen, Amy Catherine. "INHIBITION OF OSTEOCLASTOGENESIS BY SEX STEROIDS AND OTHER NUCLEAR RECEPTOR LIGANDS". University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin985626097.
Pełny tekst źródłaHadi, Tamer. "THE ROLE OF p62 IN OSTEOCLASTOGENESIS AND PAGET’S DISEASE OF BONE". VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/3312.
Pełny tekst źródłaYano, Kazuki. "Immunological Studies on the Physiopathological Functions of Osteoclastogenesis Inhibitory Factor(OCIF)". Kyoto University, 2002. http://hdl.handle.net/2433/149501.
Pełny tekst źródłaBaron, Andrew Ellis Mastro Andrea Marie. "Osteoblast-mediated osteoclastogenesis in response to breast cancer cell condition media". [University Park, Pa.] : Pennsylvania State University, 2009. http://honors.libraries.psu.edu/theses/approved/WorldWideIndex/EHT-26/index.html.
Pełny tekst źródłaAldridge, S. E. "Vascular endothelial growth factor and osteoclastogenesis : a role in metastasis to bone". Thesis, University of Newcastle upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405067.
Pełny tekst źródłaYuan, Yuyu. "The differential effects of two critical osteoclastogenesis stimulating factors on bone biomechanics". Connect to this title online, 2009. http://etd.lib.clemson.edu/documents/1252424964/.
Pełny tekst źródłaNasu, Tomonori. "EP4 agonist accelerates osteoinduction and degradation of β-tricalcium phosphate by stimulating osteoclastogenesis". Kyoto University, 2008. http://hdl.handle.net/2433/135868.
Pełny tekst źródłaGuay, Bélanger Sabrina. "Résorption osseuse, ostéoclastogénèse et adalimumab : Projet BROCA (de l'original anglais : "Bone resorption, Osteoclastogenesis and Adalimumab")". Mémoire, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6311.
Pełny tekst źródłaOliveira, Amanda Amaral Pereira de. "Avaliação do efeito do flúor na osteoclastogênese in vitro". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-19062015-163647/.
Pełny tekst źródłaThe bone tissue has a high degree of rigidity and pressure resistance, characteristic related to its protection, support and locomotion functions. Diseases such as periodontitis, osteoporosis and rheumatoid arthritis arise from dynamic bone imbalance that occurs when osteoclasts present increased activity compared to osteoblasts. Fluoride (F-) is incorporated in mineralized tissues after ingestion and its administration increases in vivo bone formation in dose and strain-dependent manner. The strains A/J and 129P3/J make possible the analysis of molecular phenomena involved in susceptibility and resistance of bone cells to the effect of F- in bone. In this study, we evaluated the effect of F- on the in vitro osteoclastogenesis, by analyzing the fosfatase tartrate-resistant acid (TRAP) activity, TRAP positive cell counts and the activity of MMP-2 and -9 measurements in A/J and 129P3/J differentiated hematopoietic stem cells. Hematopoietic cells were differentiated with M-CSF and RANKL and treated or not with F- in the concentrations of 10-9, 10-7, 10-5, 5x10-5, 5x10-5, 10-4 and 10-3 M.The data show that TRAP activity, an osteoclast marker, was similar between cells from both strains of mice, regardless of F-. In addition, the treatment of A/J cells with F- significantly increased TRAP activity, in a dose-independent manner. This was accompained by the increased TRAP+-osteoclast counts, at 10-3 M F- dose. However, while the MMP-9 activity was aumented when compared to MMP-2, it was not altered by F-, regardless of the strain. Thus, we concluded that cells from both strains do not differ regarding the osteoclast differentiation potential, but they respond differently to F-, whereas A/J and 129P3/J cells are sensitive and resistant to F--induced osteoclastogenesis, respectively.
Olivier, Brenda Jean. "Increased osteoclastogenesis and bone resorption by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia". Diss., University of Pretoria, 2007. http://hdl.handle.net/2263/27189.
Pełny tekst źródłaMelemedjian, Ohannes Kevork. "Adverse Effects of Sustained Morphine Treatment in an Experimental Model of Bone Cancer Pain: Mechanisms That Underlie Hyperalgesia and Osteoclastogenesis". Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/194043.
Pełny tekst źródłaKylmäoja, E. (Elina). "Osteoclastogenesis from bone marrow and peripheral blood monocytes:the role of gap junctional communication and mesenchymal stromal cells in the differentiation". Doctoral thesis, Oulun yliopisto, 2018. http://urn.fi/urn:isbn:9789526221045.
Pełny tekst źródłaTiivistelmä Osteoklastit ovat monitumaisia luuta hajottavia soluja, jotka ovat erilaistuneet monosyyteistä. Monosyyttejä voidaan eristää luuytimestä tai perifeerisestä verestä. Erilaistumisen aikana osteoklastien esiastesolujen sekä muiden luusolujen, kuten mesenkymaalisten stroomasolujen (MSC) välillä tapahtuu monimutkaista signalointia. Aukkoliitoskommunikointi (GJC) on eräs solufuusiossa tapahtuvista mekanismeista. GJC:tä voidaan muunnella useilla aineilla, esimerkiksi spesifisillä stimulaattoreilla, antiarytmisillä peptideillä (AAP). AAP-yhdisteiden vaikutuksia on tutkittu laajalti sydänkudoksessa johtuen niiden lupaavista kliinisistä ominaisuuksista sydänperäisten oireiden hoidossa. Tämän tutkimuksen tarkoituksena oli selvittää GJC:n ja AAP-yhdisteiden roolia luusoluviljelmissä. Lisäksi tutkittiin MSC-solujen osallistumista AAP-yhdisteiden vaikutuksiin sekä vertailtiin kahta erilaista osteoklastogeneesiviljelmää, joissa oli eri määrä MSC-soluja. GJC:tä osteoklastogeneesissä tutkittiin sekä sitä estävillä että stimuloivilla yhdisteillä hiiren monosyyttilinjan RAW 264.7 -soluissa sekä luuytimen hematopoieettisten solujen primääriviljelmissä. Seuraavat tutkimukset tehtiin ihmisen luuytimen ja perifeerisen veren monosyyteillä, ja niissä selvitettiin AAP10-yhdisteen vaikutuksia fysiologisissa sekä happamissa olosuhteissa. Lisäksi vertailtiin luuytimen ja perifeerisen veren monosyyttien osteoklastogeneesiä. In vitro -soluviljelmät tehtiin naudan tai ihmisen luulastujen päällä, ja soluista analysoitiin monitumaisuus, luun resorptio sekä useiden osteoklastimarkkereiden ilmentyminen. Tulokset osoittavat, että GJC:tä hyödynnetään osteoklastogeneesissä, mutta se ei ole korvaamaton mekanismi. GJC:tä voidaan stimuloida AAP-yhdisteillä osteoklastogeneesin aikana, mutta vaikutukset riippuvat viljelyolosuhteista sekä MSC-solujen läsnäolosta. AAP-yhdisteet voivat aktivoida myös MSC-soluja johtaen osteoklastogeneesin epäsuoraan säätelyyn, kun MSC-solut tuottavat useita erilaistumiseen vaikuttavia molekyylejä. Lisäksi perifeerisen veren monosyyteillä havaittiin korkeampi osteoklastogeeninen erilaistumispotentiaali verrattuna luuytimen monosyytteihin. Tulokset voidaan selittää osteoklastogeneesiä säätelevien MSC-solujen läsnäololla luuydinviljelmissä, kun taas perifeerisen veren monosyyttiviljelmissä näitä soluja on vain vähän, jolloin myös niiden säätelyominaisuudet puuttuvat
Oliveira, Flávia Amadeu de. "Mecanismos intracelulares induzidos por leucotrienos durante a diferenciação osteogênica". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-24052018-182709/.
Pełny tekst źródłaLeukotrienes (LTs) are inflammatory mediators derived from the 5-lipoxygenase (5-LO) pathway, with a relevant contribution in bone resorption. In this study we investigated the role of LTs in osteogenic differentiation and its impact on osteoclastogenesis.Thus, the bone profile of the 129/Sv (WT) and 5-LO Knockout mice (5-LO KO) was evaluated by computerized microtomography, showing higher vertebral bone density and thicker trabeculae in 5-LO KO males. After that, primary osteoblasts (OBL) were isolated and cultured to determine alkaline phosphatase activity (ALP) and mineralization potential. Results showed that OBL KO has higher ALP activity and mineralization, in all periods when compared with WT. In addition, the treatment with LTB4 and LTD4 inhibited calcium deposition. Inhibitors of LT synthesis and BLT1/2 antagonists were effective to recover the mineralized nodules formation. The kinetics of Alox5 showed an increase in expression during cellular differentiation period in WT OBL. In addition, expression of OCN, MMPs 2 and 9 and RANKL were increased in 5- LO KO cells in almost all evaluated periods. In general, the stimulation with LTs, their inhibitors and antagonists decreased the expression of Sp7, Col1a1, Opg and MMP- 9. But it increased the RANKL expression in KO cells. The second messengers signaling was also evaluated. 5-LO KO cells showed lower concentration levels of intracellular calcium (Ca2+ i) when compared to WT cells. In the 14-day period, the LTD4 treatment inhibited the Ca2+i independent of the murine lineage, relative to the control. cAMP levels were lower in OBL 5-LO KO, in all treated or control groups. LTD4 decreased the concentration of cAMP, but not LTB4, in KO cells. The study also quantified the production of LTB4 and other eicosanoids in osteoblasts showing their ability to synthesize those metabolites. The proteomic analysis revealed 89 downregulated proteins in OBL KO, out of a total of 154, most of them related to cytoskeleton and energy metabolism. Also 59 identified proteins were unique in OBL 5-LO KO and 06 exclusively expressed in WT cells, revealing the intrinsic differences of each strain. The osteoclastogenic profile of WT vs. 5-LO KO showed significant differences in phenotypic analysis, TRAP and in the gene expression of cells derived from the monocyte-macrophage-lineage. After M-CSF and RANKL stimulation, WT cells showed multinucleated giant osteoclasts. However, 5-LO KO cells presented a population of cells with variable shapes and sizes, and a lower maturation stage. In addition, exogenous LTs did not modulate TRAP activity. The conditioned medium from OBL WT and 5-LO KO delayed the formation process of osteoclasts. Gene expression analysis in osteoclasts showed decreased expression of Alox 5, Il-1b, Il-6 and TNF in 5-LO KO cells. BLT1/2, CysLt1 and the osteoclast differentiation markers Acp5, Ctsk and Nfact1 showed no differences between the strains. In addition, LTB4 decreased the expression of Alox5, and IL-1b was increased in WT osteoclasts. Thus, the results demonstrate that the LTs are able to modulate the bone metabolism, and the absence of the 5-LO gene is related to the greater osteogenic profile.
Vaughan, Tanya, i n/a. "Identifying Genes Influencing Bone Mineral Density". Griffith University. School of Health Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040430.161453.
Pełny tekst źródłaRepeke, Carlos Eduardo Palanch. "Cinética de expressão de moléculas co-estimulatórias de osteoclastos no desenvolvimento da doença periodontal experimental e sua modulação por citocinas". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-08012013-164313/.
Pełny tekst źródłaThe osteoclast differentiation and activation are essential to bone tissue homeostasis and in the development of bone pathologies, which RANK/RANKL signaling molecules are the major osteoclastogenic factor. However, osteoclast co-stimulatory molecules, such as DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A, also present an important role in the osteoclastogenesis. However, the exact role and regulation of these molecules in human and mice periodontal diseases (PD) development have not completely known. Our aim was to investigate the pattern of osteoclast co-stimulatory expression (DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A) in human chronic periodontitis (CP), apart from analyze the kinetic of these molecules and their regulation by cytokines (TNF-, IFN-, IL-17 and IL-10) in the development of experimental periodontal disease in mice C57Bl/6 and knockout. Our results demonstrated that all osteoclast co-stimulatory molecules presented highly expressed in CP patients when compared with control. Similar results are presented about experimental PD, where all co-stimulatory molecules was presented highly expressed in infected mice when compared with control mice. We observed in TNFp55KO, IFNKO and IL17KO mice a decrease in PD scores and co-stimulatory molecules expression, the opposite of IL10KO mice. However, when we standardized the co-stimulatory molecules levels by the number of inflammatory cells, we found that TNF- and IL-17 are associated with increased expression of co-stimulatory molecules, while IFN- and IL-10 appear to negatively regulate the expression of such molecules. In conclusion, we demonstrated that osteoclast co-stimulatory molecules shown increased in human and experimental PD, and cytokines appear to modulate their expression by direct and indirect mechanisms, such as inflammatory cells migration to the PD infected tissue.
Vaughan, Tanya. "Identifying Genes Influencing Bone Mineral Density". Thesis, Griffith University, 2004. http://hdl.handle.net/10072/366470.
Pełny tekst źródłaThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
Full Text
Kagwiria, Rosebeth [Verfasser], i Lars [Gutachter] Nitschke. "Evaluation of the nuclear receptor Retinoic Acid Receptor related Orphan Receptor α (RORα) as a regulator of osteoclastogenesis in rheumatoid arthritis and osteoporosis / Rosebeth Kagwiria ; Gutachter: Lars Nitschke". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2017. http://d-nb.info/1140228609/34.
Pełny tekst źródłaAmaral, Bruna Aguiar do. "Imunoexpress?o de fatores reguladores da osteoclastog?nese na doen?a periodontal em humanos e sua rela??o com os par?metros cl?nicos". Universidade Federal do Rio Grande do Norte, 2011. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17150.
Pełny tekst źródłaPeriodontal disease is an infection initiated by oral periodontal pathogens that trigger an immune response culminating in tissue destruction. This destruction is mediated by the host by inducing the production and activation of lytic enzymes, cytokines and the stimulation of osteoclastogenesis. The aim of this study was to compare the immunohistochemical expression of factors involved in bone resorption, RANKL (Ligand Receptor Activator of Nuclear Factor kappa B), OPG (Osteoprotegerin) and TNF-α (tumor necrosis factor alpha) between the gingival healthy, gingivitis and chronic periodontitis and correlate them with clinical parameters. The sample consisted of 83 cases and 12 clinically healthy gums, 42 gingivitis and 29 periodontitis, from 74 adolescent and adult patients with a mean age of 35 years, without systemic changes and non-smokers, predominantly female and race brown. There was no statistically significant difference for the expression of anti-RANKL (p = 0.581) and RANKL / OPG ratio (p = 0.334) when comparing the three conditions, but the anti-OPG and anti-TNF-α showed statistically significant between the types of injury (p = 0.001 and p <0.001, respectively), showing greatest expression in periodontitis. In cases of periodontitis, the variable clinical attachment loss (PIC) was statistically significant and positive correlation, respectively, with immunostaining of anti-RANKL (p = 0.002, p = 0.001 and r = 0.642), anti-OPG (p = 0.018, p = 0.014 and r = 0.451), anti-TNF-α (p = 0.032, p = 0.014 and r = 0.453) and the percentage ratio of RANKL / OPG (p = 0.018, p = 0.002 and r = 0.544). The tooth mobility (MB) showed a statistically significant difference only with immunohistochemical anti-RANKL (p = 0.026), and probing depth (PD) was positively correlated with anti-RANKL (p = 0.028 and r = 0.409), both in cases of periodontitis. Only in cases of gingivitis TNF-α was positively correlated with RANKL (p = 0.012 and r = 0.384) and the RANKL / OPG ratio (p = 0.027 and r = 0.341). Given these results, we conclude that the greatest expression of TNF-α in periodontitis demonstrates a relationship with the progression and severity of periodontal disease and the correlation between all antibodies and clinical attachment loss demonstrates their involvement in periodontal bone resorption
A doen?a periodontal ? uma infec??o oral iniciada por periodontopat?genos que desencadeiam a resposta imune culminando com a destrui??o tecidual. Essa destrui??o ? mediada pelo hospedeiro atrav?s da indu??o da produ??o e ativa??o de enzimas l?ticas, citocinas e da estimula??o da osteoclastog?nese. O objetivo deste estudo foi comparar a express?o imuno-histoqu?mica dos fatores envolvidos na reabsor??o ?ssea, RANKL (Ligante do Receptor Ativador do Fator Nuclear kappa B), OPG (Osteoprotegerina) e TNF-α (Fator de Necrose Tumoral Alfa) entre a gengiva clinicamente saud?vel, a gengivite e a periodontite cr?nica, correlacionando-os com os par?metros cl?nicos periodontais. A amostra consistiu de 83 casos, sendo 12 de gengivas clinicamente saud?veis, 42 de gengivite e 29 de periodontite, oriundos de 74 pacientes adolescentes e adultos com idade m?dia de 35 anos, sem altera??es sist?micas e n?o fumantes, predominantemente do sexo feminino e da ra?a parda. N?o houve diferen?a estatisticamente significativa para express?o do anticorpo anti-RANKL (p=0,581) e da raz?o RANKL/OPG (p=0,334) quando se comparou as tr?s condi??es cl?nicas, mas o anti- OPG e anti-TNF-α mostraram diferen?as estatisticamente significativas entre os tipos de les?o (p=0,001 e p<0,001, respectivamente), revelando maior imunoexpress?o na periodontite. Nos casos de periodontite, a vari?vel perda de inser??o cl?nica (PIC) mostrou diferen?a estatisticamente significativa e correla??o positiva, respectivamente, com a imunomarca??o dos anticorpos anti-RANKL (p=0,002; p=0,001 e r=0,642), anti-OPG (p=0,018; p=0,014 e r=0,451), anti-TNF-α (p=0,032; p=0,014 e r=0,453) e com a raz?o percentual de RANKL/OPG (p=0,018; p=0,002 e r=0,544). A mobilidade dent?ria (MB) apresentou diferen?a estatisticamente significativa somente com a imunoexpress?o do anti-RANKL (p=0,026), e a profundidade de sondagem (PS) apresentou correla??o positiva com o anti- RANKL (p=0,028 e r=0,409), ambos nos casos de periodontite. Somente nos casos de gengivite o TNF-α apresentou correla??o positiva com o RANKL (p=0,012 e r=0,384) e com a raz?o RANKL/OPG (p=0,027 e r=0,341). Diante desses resultados, conclui-se que a maior imunoexpress?o do TNF-α na periodontite demonstra uma rela??o com a progress?o e severidade da doen?a periodontal e a correla??o entre todos os anticorpos e a perda de inser??o cl?nica demonstra o envolvimento destes na reabsor??o ?ssea periodontal
Tan, Jamie We-Yin. "The investigation of RANKL TNF-like core domain by truncation mutation". University of Western Australia. School of Surgery and Pathology, 2003. http://theses.library.uwa.edu.au/adt-WU2004.0032.
Pełny tekst źródłaAllard-Chamard, Hugues. "Localisation et implication des phospholipases A[indice inférieur 2] cytosolique et sécrétée dans le contrôle de l’ostéoclastogénèse et des fonctions ostéoclastiques chez l’humain". Thèse, Université de Sherbrooke, 2014. http://hdl.handle.net/11143/5864.
Pełny tekst źródłaSantos, Fernanda Regina Ribeiro. "Ciclooxigenase-2 modula in vivo a expressão de marcadores da osteoclastogênese e genes envolvidos no metabolismo ósseo em resposta ao lipopolissacarídeo bacteriano". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/58/58135/tde-04072012-135640/.
Pełny tekst źródłaDuring an inflammatory response, several mediators are locally released in order to stimulate cellular and humoral immune response. Through the action of cyclooxygenase and lipoxygenase enzymes structural changes occur in the arachidonic acid chain leading to synthesis of prostaglandins or leukotrienes and lipoxins, respectively. Such mediators are responsible for the regulation of RANK, RANKL and OPG gene expression, osteoclastogenesis modulators. Thus, the objective of this study was to evaluate the expression of messenger RNA (mRNA) for the enzymes involved in arachidonic acid metabolism, cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO), and the osteoclastogenesis mediators (RANK, RANKL and OPG) in bone tissue after injection of bacterial lipopolysaccharide (LPS) in murine dental root canals. Then, COX-2 pathway was pharmacologically blocked for investigation of expression of osteoclastogenesis mediators and genes involved in bone metabolism. We used 144 C57BL/6 mice, 6 weeks-old, weighing 18-20 grams, which had the first molars root canals inoculated with a solution containing LPS from E. coli (0.1, 1.0 and 10 mg/ml). After 7, 14, 21 and 28 days the animals were euthanized and the tooth-and-bone blocks were removed for total RNA extraction. Subsequently, the evaluation of gene expression was performed by reverse transcription and polymerase chain reaction in real time (qRT-PCR). Global analysis of mRNA expression for proteins involved in bone metabolism was performed using PCR arrays (Osteogenesis RT² Profiler PCR Array). The values for relative expression of each mRNA for each group were compared using two-way analysis of variance (ANOVA) followed by Bonferroni post-test or one-way ANOVA followed by Dunnett\'s test (α=0.05). The injection of LPS into the root canals was induced expression of genes PTGS2 and ALOX5, responsible for encoding COX-2 and 5-LO enzymes, involved in the metabolism of arachidonic acid, simultaneously to the modulation of gene expression of TNFRSF11A, TNFSF11 and TNFRSF11B, responsible for encoding the osteoclastogenesis modulators RANK, RANKL and OPG, respectively. Administration of Indomethacin, a non-selective inhibitor of COX-2, inhibited the expression of mRNA for RANK and RANKL and stimulated the expression of OPG during the initial response to the root canals contamination with LPS. Inhibition of the COX-2 pathway from arachidonic acid metabolism in the initial periods of response to LPS injection into the root canals differentially modulated the expression of genes involved in bone catabolism and anabolism, indicating possible roles for mediators derived from arachidonic acid in the regulation of bone metabolism. These results suggest important therapeutic targets for early intervention in inflammatory diseases such as apical periodontitis to avoid resorption of bone tissue.
Franco, Gilson Cesar Nobre. "Analise da farmacocinetica e dos indices PK/PD da doxiciclina no plasma, fluido gengival e saliva e avaliação de seu efeito sobre a osteoclastogenese mediada por RANKL". [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288516.
Pełny tekst źródłaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Doxiciclina (Dox) é um antimicrobiano pertencente à família das tetraciclinas com um amplo espectro de ação contra bactérias Gram-positivas e Gram-negativas. Além de suas propriedades antimicrobianas, Dox é atualmente empregada na periodontia como um modulador da resposta do hospedeiro (MRH), ao inibir a atividade da enzima metaloproteinase de matriz (MMP), a qual está relacionada ao processo de destruição tecidual. Neste contexto, este trabalho teve os seguintes objetivos: 1-determinar os parâmetros farmacocinéticos e integrar os índices PK/PD da Dox para o plasma, fluido gengival (FG) e saliva; 2-analisar os efeitos in vitro e in vivo da Dox sobre a osteoclastogênese com a finalidade de elucidar possíveis propriedades biológicas adicionais deste fármaco como MRH. Para a análise farmacocinética, 12 voluntários receberam dose oral única de 100 mg de Dox. Sangue, FG e saliva foram coletados em tempos pré-determinados e a concentração da Dox nestes fluidos foi determinada por bioensaio. A análise dos principais índices PK/PD da Dox foi realizada considerando o CIM para P. gingivalis. Para o segundo objetivo, o efeito da Dox sobre os processos de diferenciação e ativação osteoclástica foi verificado, respectivamente, pela contagem de células TRAP+ multinucleadas geradas a partir de células precursoras estimuladas com sRANKL na presença ou ausência de Dox e pela análise das lacunas de reabsorção formadas por estas células, quando cultivadas sobre discos de dentina. In vivo, o efeito da Dox sobre a osteoclastogênese foi determinado através da indução deste processo em calvária de camundongo. Solução de sRANKL/LPS foi injetada na região da calvária e os animais receberam, por gavagem, Dox ou placebo diariamente. Após 10 dias, a calvária foi removida para análise histoquímica. Em acréscimo, a atividade da Dox sobre a expressão de genes responsáveis pelos processos de diferenciação e ativação osteoclástica foi analisada por RT-PCR. Durante os experimentos in vitro e in vivo, a produção e atividade da MMP foram verificadas através de Western-blot e Zimograma respectivamente. Os resultados demonstraram que as maiores concentrações de Dox foram observadas no plasma, seguido pelo FG e saliva. A análise dos índices PK/PD da Dox indicou que a dose de 100 mg foi insuficiente para se obter os valores ideais antimicrobianos preconizados na /CIM. Os experimentos in vitro e in vivo sobre o efeito da Dox como MRH demonstraram que este fármaco inibiu os processos de diferenciação e ativação dos osteoclastos. Dox também modulou a expressão de proteínas diretamente relacionadas a osteoclastogênese, incluindo TRAP, Catepsina K e c-Myc. Finalmente, embora a síntese da MMP não tenha sido afetada, a atividade da MMP foi reduzida na presença de Dox. Portanto, os resultados do presente estudo sugerem que uma dose inicial maior do que 100 mg é necessária para alcançar o valor preconizado para ASC/CIM e Cmax/CIM, com a finalidade de se obter os melhores resultados clínicos antimicrobianos. A análise da Dox como MRH indicou que este fármaco pode atuar neste processo não somente pela sua capacidade de inativar a MMP, e sim, por apresentar a propriedade de inibir a diferenciação e ativação osteoclástica, incluindo a modulação de sua expressão gênica. literatura para os parâmetros ASC/CIM e Cmax
Abstract: Doxycycline (Dox), a member of the tetracycline family, is an antimicrobial agent with a broad-spectrum of activity against Gram-positive and Gram-negative bacteria. In addition to its antimicrobial properties, Dox is used in the treatment of periodontal diseases as a host response modulator by inhibiting the activity of an important enzyme, matrix metalloproteinase (MMP), which is related to the process of tissue destruction. In this context, this study had the following aims: 1-to determine the pharmacokinetic parameters of Dox and to integrate the PK/PD indices for plasma, gingival crevicular fluid (GCF) and saliva; 2-to analyze the effects in vitro and in vivo of Dox on the osteoclastogenesis and on the osteoclast activation in order to elucidate additional biological properties of Dox on the host response modulation (HRM). Twelve volunteers received single oral administration of Dox (100 mg). Blood, GCF and saliva were collected and the concentrations were measured by bioassay technique. The PK/PD analyses were carried out using the MIC for P. gingivalis. For the second objective, the effect of Dox on the osteoclast differentiation and activation processes was determined, respectively, by the counting of TRAP+ multinuclear cells derived from osteoclast precursory cells sRANKL-stimulated in the presence or absence of Dox and by the analysis of the resorption areas formed by these cells when cultured on dentin discs. In vivo, Dox¿s effect on the osteoclastogenesis was verified using the model of osteoclastogenesis induction in mouse calvaria. sRANKL/LPS was injected in the supra-calvaria area and the animals received Dox or placebo daily by gavage. After the experimental period of 10 days, the calvariae were removed for histochemistry analyses. In addition, the effect of Dox on the expression of genes related to the osteoclast differentiation and activation processes was carried out using RT-PCR technique. MMP production and activity were ensured during in vitro and in vivo experiments by Western-blot and Zymography, respectively. The results demonstrated that Dox achieved the highest concentration in the plasma, following by GCF and saliva. PK/PD analyses showed that the dose of 100 mg was insufficient to get the antimicrobial levels indicated in the literature for AUC/MIC and Cmax/MIC indices. In vitro and in vivo studies of Dox¿s effects on the HRM demonstrated that this drug could inhibit the osteoclast differentiation and activation process. Dox also showed an important property of down-regulation in the expression of proteins directly related to osteoclastogenesis, including TRAP, Cathepsin K and c-Myc. Finally, although Dox did not affect the expression of MMP protein, MMP activity was remarkably decreased by Dox. Therefore, the present study suggests that higher doses than 100 mg would be necessary to obtain effective antimicrobial levels and the effect of DOX on the HRM can be due to not only by MMP inhibition but also by the direct effect on RANKL-mediated osteoclast differentiation and activation, including its gene regulation
Doutorado
Farmacologia, Anestesiologia e Terapeutica
Doutor em Odontologia
Tardini, Gianmarco. "Studio dell'osteoclastogenesi tramite analisi di immagini di microscopia confocale in fluorescenza". Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amslaurea.unibo.it/24032/.
Pełny tekst źródłaYin-BoJou i 周吟柏. "The role of thrombomodulin in osteoclastogenesis". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/82001440654877487602.
Pełny tekst źródła國立成功大學
生物化學暨分子生物學研究所
101
Backgrounds:Thrombomodulin (TM), a glycoprotein on the cell surface, is highly expressed in endothelial cells and other numerous cell types such as keratinocyes, osteoblasts and myeloid mononuclear cells. It is first discovered as an anticoagulant factor, and recent studies demonstrate that it has multi-functions including angiogenesis, cell proliferation and complement activation. TM in monocytes/macrophages is associated with inflammation and the expression level is altered in physiological and pathological conditions. In osteoclastogenesis, monocytes /macrophages obtained from bone marrow or vascular-blood system can differentiate to osteoclasts by cell-cell fusion to form multinucleated cells, which are involved in bone resorption. Until now, the role of TM in macrophages in osteoclastogenesis has not been investigated. Materials and Methods:Osteoclast precursors were isolated from human peripheral blood mononuclear cells (PBMCs) and mouse bone marrow derived macrophages (BMMs). Myeloid-specific TM-deficent mice (LysMcre/TMflox/flox) and mice lacking lectin-like domain of TM (TMLeD/LeD) were used. The differentiation was induced by macrophage-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL). Results:TM expression was decreased during osteoclastogenesis. Results of osteoclast formation from LyMCreTMflox/flox BMMs showed that TM deficiency caused enhancement of osteoclastogenesis. TMLeD/LeD mice BMMs also had higher activity of osteoclast formation, indicating that TM lectin-like domain plays a role in osteoclastogenesis. Finallly, the proinflammatory cytokine high mobility group box 1 (HMGB1) production in LysMCreTMflox/flox BMMs was much more than TMflox/flox group after RANKL treatment, which suggested that TM regulates osteoclastogenesis by interfering the function of HMGB1 in osteoclasts. Conclusion:Taken together, we showed that TM expression was inversely correlated with the differentiation of osteoclasts. It was speculated that TM may participate in osteoclastogenesis through modulating inflammatory response and which may provide a novel application on osteometabolic diseases.
Lee, Be-Han, i 李碧涵. "Role of TRAF6 in TRAIL-induced osteoclastogenesis". Thesis, 2008. http://ndltd.ncl.edu.tw/handle/60467519479490721550.
Pełny tekst źródła國立臺灣大學
免疫學研究所
96
Osteoclasts are multinucleated cells (MNCs) that are differentiated from macrophage/ monocyte lineage of hematopoietic precursors. Receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL), a tumor necrosis factor (TNF) family cytokine, plays a key role in osteoclast differentiation. RANKL binds to its receptor RANK, which recruits TNF receptor associated factor 6 (TRAF6) and activates NF-κB, Akt, and mitogen-activated protein kinase (MAPK) pathways finally leading to osteoclast-specific genes expression. In addition to RANKL, more and more studies indicated that some TNF family members including TNF-α, FasL and LIGHT are involved in differentiation and function of osteoclasts. These studies suggested that some TNF-family cytokines may regulate osteoclast differentiation. In addition to induction of apoptosis, TNF-related apoptosis inducing ligand (TRAIL) exerts different function that includes survival, proliferation and maturation. Our previous studies have demonstrated that TRAIL can induce osteoclasts differentiation from murine monocytic cell line, RAW 264.7 and human peripheral mononuclear cells (PBMCs), and this signaling pathway is distinct from apoptosis signaling. TRAIL could activate NF-κB and MAPKs, which are important for RANKL-induced osteoclastogenesis. However, the signaling pathway that leads to downstream molecules activation and resulting in osteoclastogenesis remains unclear. TRAF6 is critical in RANKL-induced osteoclastogenesis. Cells from TRAF6-deficient mice can not differentiate into osteoclasts in the presence of RANKL. Therefore, we hypothesize that TRAIL stimulation activates MAPKs and NF-κB pathways to induce osteoclastogenesis through adaptor molecule, TRAF6. To determine whether TRAF6 is involved in TRAIL-induced osteoclastogenesis, we used TRAF6 siRNA to inhibit TRAF6 expression. After knockdown TRAF6 expression by transfection of TRAF6 siRNA, we found that similar to RANKL, osteoclast formation was reduced after TRAIL stimulation. We further investigated whether suppression of TRAF6 expression might affect TRAIL-induced NF-κB and MAPKs activation. Our results demonstrated that knockdown TRAF6 expression reduced TRAIL-induced MAPK activation. In conclusion, TRAIL induces osteoclast differentiation via activation of MAPK which is dependent on TRAF6. Our results provide a novel mechanism that TRAIL can transduce a non-apoptotic signal mediated by TRAF6 to induce osteoclast formation.
Lee, Be-Han. "Role of TRAF6 in TRAIL-induced osteoclastogenesis". 2008. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2807200816075200.
Pełny tekst źródłaApfeldorfer, Coralie [Verfasser]. "Lysosome biogenesis during osteoclastogenesis / presented by Coralie Apfeldorfer". 2006. http://d-nb.info/982567227/34.
Pełny tekst źródłaTorres, Ana Luísa Pereira da Silva. "The influence of modified chitosan substrates on osteoclastogenesis". Master's thesis, 2011. http://hdl.handle.net/10216/64677.
Pełny tekst źródłaTorres, Ana Luísa Pereira da Silva. "The influence of modified chitosan substrates on osteoclastogenesis". Dissertação, 2011. http://hdl.handle.net/10216/64677.
Pełny tekst źródłaChen, Yu-Ling, i 陳譽齡. "Effects of Shampignons Exposed to Radiation on Osteoclastogenesis". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/xjdnmg.
Pełny tekst źródła慈濟科技大學
放射醫學科學研究所
106
Abstract Shampinon belongs to agaricus mushrooms, of which the extract is rich in beta glucan and represents anti-oxidation and anti-inflammatory effects. Another extract, ergosterol, will be converted to vitamin D2 via radiation exposure. Some factors such as free radicals and inflammatory cytokines can induce osteoclast differentiation. Clinically, chronic inflammation often leads to loss of bone mass, while vitamin D2 has the role of slowing osteoclastogenesis. It is not known whether giving Shampinon extracts affects osteoclastogenesis, and there is no relevant literature to explore. The purpose of this experiment is to study the Shampinon (by radiation 5 Gy or no radiation treatment) biological effects of extracts on osteoclast differentiation and its possible mechanism. In this experiment, Raw264.7 cells from mouse mononuclear cell line were taken, and osteoclast-inducing agent RANKL was added to extracts. The toxicity of extracts on cells was evaluated by MTT assay. Safe dose of Shampinon extracts were added into the culture medium to investigate the osteoclastogenesis. Shampinon extracts were taken to assess the expression of oxygen free radicals (ROS) and CD51 (a cell marker of osteoclast precursor). To assess osteoclast activity, the number of osteoclasts and the amount of enzyme of tartrate-resistant acid phosphatase (TRAP) were analyzed. Results show that the extracts of Shampinon exposed to radiation will inhibit the CD51 marker expression and the number of osteoclast significantly less than the control group. The osteoclast activity of TRAP and ROS in cells were also inhibited. After exposed to radiation, the ergosterol was converted to vitamin D2 using High-performance liquid chromatography (HPLC) assay. The results suggest that Shampinon extracts have inhibition effects on osteoclastogenesis, which is probably via inhibiting the number of preosteoclast.
Hassanpour, Siavash. "Adseverin is a Key Regulator and Marker of Osteoclastogenesis". Thesis, 2010. http://hdl.handle.net/1807/25614.
Pełny tekst źródłaTseng, Feng-Jen, i 曾豐仁. "To Investigate the Effects of Carbon Monoxide on Osteoclastogenesis". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/5jr9np.
Pełny tekst źródła國立東華大學
生命科學系
107
Bone is a dynamic tissue that is continuously formed by osteoblasts and resorbed by osteoclasts in response to changes in mechanical loading, altered serum calcium levels and a wide range of paracrine, endocrine and neuronal factors. Any unbalances between bone formation and resorption will lead to diseases such as osteopetrosis or osteoporosis. The principle bone-resorbing osteoclasts are giant multinucleated cells derived from hematopoietic precursors of the monocyte-macrophage lineage. Bone loss due to osteoclasts over activity is very common in many inflammatory bone disorders such as rheumatic arthritis (RA), septic arthritis and periprosthetic osteolysis. Thus, understanding of the regulation of osteoclasts differentiation and function is central to the treatment these diseases. Formation of functional and mature osteoclasts requires many factors such as macrophage colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). The expression of RANKL is regulated by many factors including inflammatory cytokines. Carbon monoxide (CO), a ubiquitous air pollutant, has been well known as toxic because its affinity to hemoglobin is 240 times compares with oxygen thus causing hypoxia and death. However, low concentration CO has been proved to be useful in anti-oxidative stress, anti-proliferation and anti-inflammation in vivo and in vitro. CO releasing molecule can also reduce RANKL expression and bone erosion in murine collagen-induced arthritis model. These previous results imply that CO might affect osteoclastogenesis to a certain extent. The aims of this proposal are: (1) to set up an osteoclastogenesis model by the murine monocytic cell line, RAW 264.7 cells, stimulated with RANKL, (2) to investigate the effects of CO on osteoclastogenesis, (3) to explore the possible molecules mediating the effects of CO. We expect this study will probably reveal some novel therapeutic implication of CO.
Nilforoushan, Dorrin. "Involvement of Nitric Oxide in Osteoclastogenesis and Orthodontic Tooth Movement". Thesis, 2009. http://hdl.handle.net/1807/19066.
Pełny tekst źródłaLin, Ru-Wei, i 林儒緯. "Effects of Green Tea Catechins and Ipriflavone Derivatives on Osteoclastogenesis". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/45508645744098309768.
Pełny tekst źródła高雄醫學大學
藥學研究所
97
Abstract Osteoporosis is a significant disease in geriatrics. A nutritional approach to reduce bone loss would be a future goal to achieve an inexpensive way for managing osteoporosis. Previous epidemiological studies found that people with a habit of tea drinking have higher bone mineral density and less chance to get hip fracture. Green tea catechin, (−)-epigallocatechin gallate (EGCG), increased the osteogenic function in mesenchymal stem cells was reported. The effect of EGCG on osteoclastogenesis remains to be elucidated. In this study, we investigated the influence of EGCG on osteoclasts and found that treatment of EGCG (10–100 μM) significantly suppressed nuclear factor-kB ligand-induced osteoclast differentiation and pit formation in murine RAW 264.7 cells, the precursor cells of osteoclasts, and primary bone marrow macrophages cells (BMMs). We also identified that EGCG targets at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms revealed that EGCG significantly inhibited RANKL-induced NF-κB transcriptional activity by reducing nuclear transport of NF-κB. The results demonstrate that EGCG is a potent inhibitor of osteoclastogenesis via a mechanism involving NF-κB and TRAP gene. Our results also indicate that the possibility of EGCG to become a new strategy against bone resorption. Ipriflavone is a synthetic isoflavone derivative, which has been suggested to be an inhibitor of bone resorption in vitro and in vivo. Several clinical studies suggested that ipriflavone is able to prevent bone loss. We have screened over 150 ipriflavone derivatives by the tartrate resistant acid phosphatase (TRAP) activity of RAW 264.7 cells after RANKL induction for osteoclastogenesis. The results indicated that 3-(3,4-dimethoxyphenyl)-7-(oxiran-2-ylmethoxy)-4H-chromen-4- one (19) and 3-{4-[3-(cyclohexylamino)-2-hydroxypropoxy]phenyl}- 7-methoxy- 4H-chromen-4-one (20a) exhibited significant inhibitory effects on osteoclast activity (TRAP activity in RAW 264.7 with an IC50 of 0.56 and 2.28 μM, respectively). The results imply that these two compounds can be candidates for the discovery of anti-osteoporotic drug.
Conceição, Francisco Pereira dos Santos. "The Role of Y' Receptor in Osteoclastogenesis and Bone Resorption". Master's thesis, 2015. https://repositorio-aberto.up.pt/handle/10216/94580.
Pełny tekst źródłaConceição, Francisco Pereira dos Santos. "The Role of Y' Receptor in Osteoclastogenesis and Bone Resorption". Dissertação, 2015. https://repositorio-aberto.up.pt/handle/10216/94580.
Pełny tekst źródłaLin, Shiuan-Yea, i 林萱雅. "Study the Role of Serotonin 2B Receptor (5-HT2BR) in Osteoclastogenesis". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/r9236e.
Pełny tekst źródła高雄醫學大學
醫學系生理學科碩士班
103
Osteoporosis is the common diseases in menopausal women and elderly people, and its incidence just lower than cardiovascular disease. Excessive osteoclastogenesis is one of the main reasons to cause osteoporosis. Recent clinical researches indicated that the patients’ long-term use of anti-depression drugs (Selective Serotonin Reuptake Inhibitor, SSRI) usually with higher risk to suffer osteoporosis. This observation means serotonin, 5-HT, should involve in the regulation of bone metabolism. Previous reports showed that 5-HT 2B receptor (5-HT2BR) is expressed in both osteoblasts and osteoclasts, and which modulate the proliferation and differentiation in osteoblasts. However, the effects of 5-HT2BR in osteoclasts remain unclear. Using RANKL-induced osteoclastogenesis in RAW 264.7 cells as the model, our results presented a positive correlation between the osteoclastogenesis with 5-HT and 5-HT2BR agonist treatment and that decrease SirT1 expression. On the contrary, treatment with specific 5-HT2BR antagonist significantly reduced the osteoclastogenesis and increase SirT1 expression. Treatment with SirT1 agonist significantly reduced the osteoclastogenesis. Taken together, this investigation suggested that 5-HT2BR play an essential role in osteoclastogenesis and may be involved in regulating osteoporosis. Our observations might also provide another direction of prophylaxis and therapy for osteoporosis.
Silva, Soraia Patrícia Caetano da. "Osteoclastogenesis, inflammatory cytokines and biomarkers of bone metabolism in psoriatic arthritis". Master's thesis, 2015. http://hdl.handle.net/10362/16201.
Pełny tekst źródłaHuang, Ching-Yun, i 黃慶芸. "2-methoxystypandrone, a naphthoquinone isolated from Polygonum cuspidatum prevents RANKL-induced osteoclastogenesis". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/626rfq.
Pełny tekst źródła國立陽明大學
藥理學研究所
97
Osteoporosis is common in menopause women and old people. When the bone resorption exceeds the bone formation, a net loss of bone occurs. Inhibition of the differentiation of osteoclasts is a potential strategy to treat the osteoporosis. Previous studies showed that the binding of the receptor activator of nuclear factor �羠 ligand (RANKL) to its receptor RANK can activate mitogen-activated protein kinases (MAPKs) and trigger activation of the transcription factors, such as NF-�羠, activating protein-1 (AP-1) and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), to promote osteoclastogenesis, the generation of the tartrate-resistant acid phosphatase (TRAP) as well as bone resorption. 2-Methoxystypandrone (2MS) is a naphthoquinone compound isolated from Polygonum cuspidatum. The present results showed that 2MS (1-7.5 �嵱) concertration-dependently inhibited RANKL-induced the differentiation of RAW 264.7 macrophages into osteoclasts and the TRAP activity with an IC50 value of 6.8 �嵱 without significant cytotoxicity. Incubation the cells with RANKL significantly increased the nuclear expression of NF-�羠, c-Fos, c-Jun and NFATc1, the phosphorylation of p38, ERK and JNK, and the degradation of I�羠. All these phenomena were concentration-dependently suppressed by 2MS. Metalloproteinase-9 (MMP-9) is a digest enzyme participated in bone resorption. RT-PCR analysis revealed that RANKL-induced MMP-9 mRNA expression was inhibited by 2MS. In conclusion, the present results indicated that 2MS can inhibit RANKL-induced osteoclastogenesis probably via attenuating RANKL-induced phosphorylation of p38, ERK and JNK, the degradation of I�羠, and interfering with the activation of transcription factors (NF-κB, c-Jun, c-Fos and NFATc1).
Kuo, Ting-Hao, i 郭廷濠. "Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/02135079789878535306.
Pełny tekst źródła國立臺灣大學
藥理學研究所
103
As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2- (dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclast’s early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.
Chen, Chun-Liang, i 陳俊良. "Synthesis and Biological Evaluation of Salicylanilide Derivatives as RANKL-Induced Osteoclastogenesis Inhibitors". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/00818442085569545451.
Pełny tekst źródła國防醫學院
生命科學研究所
102
Inhibition of osteoclast formation is a potential strategy to prevent inflammatory bone resorption and treat bone disease. The development of potential antiosteoclastogenic agent is the focus of the present study. Herein, we designed and synthesized the modified salicylanilides and 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione analogues as osteoclastogenesis inhibitors. To investigate the biological activities of these synthetic compounds, we initially evaluated their effects on RANKL-induced osteoclastogenesis from osteoclast precursor cells RAW264.7 by TRAP stain as well as cell cytotoxicity by MTT assay. The most potent compounds 1d and 5d exhibited the strongest antiosteoclastogenic effects, which were selected as candidates for further antiosteoclastogenic evaluation. Both compounds 1d and 5d suppressed RANKL-induced osteoclast differentiation and TRAP activity in a dose-dependent manner. The mechanism study indicated that 1d and 5d could reduce the level of transcription factors NF-κB and NFATc1 in nucleus, and suppress the gene expression levels of osteoclastogenesis-related marker genes during osteoclastogenesis. In addition, 1d and 5d prevented osteoclastic bone resorption dose-dependently, but did not impair osteoblast differentiation in MC3T3-E1. The preliminary structure-activity relationships (SARs) of our novel synthetic compounds described the optimization and modification to a new more potent antiosteoclastogenic inhibitor. Also, salicylanilide and 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione, especially 1d and 5d, could be the novel lead structures for the development of antiresorptive agents.