Дисертації з теми "Vitamin D; bone cells"
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McIntyre, Christopher William. "Studies into the effects of non-calcaemic vitamin D sterols on bone cells." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391629.
Повний текст джерелаZarei, Allahdad. "Comparison of the effects of vitamin D metabolites on osteoblast and osteocyte bone cells." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:8d363814-c1e5-4f16-929d-18ac9debde75.
Повний текст джерелаMacoritto, Michael. "Mechanisms of vitamin D receptor and retinoid X receptor mediated hormone resistance and cell differentiation in normal and cancer cells." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111887.
Повний текст джерелаMason, Shelley S. "Exploring Tissue Engineering: Vitamin D3 Influences on the Proliferation and Differentiation of an Engineered Osteoblast Precursor Cell Line During Early Bone Tissue Development." PDXScholar, 2013. https://pdxscholar.library.pdx.edu/open_access_etds/1000.
Повний текст джерелаZylbersztejn, Florence. "Etude du rôle du récepteur à la vitamine D (VDR) dans l'hématopoïèse normale et dans les Leucémies Aiguës Myéloïde -lien avec la voie des Bone Morphogenetic Protein." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS480.
Повний текст джерелаOne of the most important causes of failure in the management of cancer is relapse, due to cancer stem cells persistence. Acute Myeloid Leukemias (AML) are the major form of acute leukemia in adults and are characterized by excessive proliferation of immature cells and apoptosis defect. At the top of the clonal hierarchy, leukemic stem cells (LSC) through their functional abilities participate in the initiation and maintenance of the disease. These cells are regulated both extrinsically mechanisms through the microenvironment and intrinsically by transcription factors.Our team is working on the Vitamin D Receptor (VDR) and its ligand Vitamin D (VD) and has demonstrated a synergistic action between iron chelation and VD in order to lift the differentiation blocking of AML with reduced toxicity (Callens et al, JEM 2010). A retrospective clinical study was conducted showing that a high vitamin D level in patients with AML before any treatment gives them a better prognosis (Paubelle, Zylbersztejn et al, Plos One 2013). We are continuing this project on the study of the VD/VDR pathway in the maintenance of hematopoietic stem cells (HSC) and its deregulation in AML. My project aims to determine the involvement of the tumor microenvironment (BMP and VDR pathway) in the maintenance of AML-LSC. Our working hypothesis is that the vitamin D receptor, in addition to its known differentiating role, would have an impact on the maintenance of normal HSC and AML and that its mechanism of action would be through the Bone Morphogenetic Protein pathway. We first demonstrated the importance of VDR in the regulation of HSCs and tested the interest of the use of its ligand to specifically target LSC in pre-clinical models. Finally we were able to confirm the deregulation of this pathway in primary AML cells and the regulation of this receptor by the Bone Morphogenetic Protein pathway. These works open up new perspectives in the understanding in CSH biology and their deregulation in AML
Dias, Cristiane Bitencourt. ""Doença óssea em glomerulopatia primária"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5148/tde-31052006-161424/.
Повний текст джерелаThe objective of this study was to analyze bone metabolism in proteinuria glomerular patients not having previously used drugs affecting bone metabolism. Seventeen patients were studied with histomorphometric analysis of bone biopsies and bone fragments were obtained for cell culture (n = 13), in which we evaluated osteoblastic proliferation. Comparing patients to controls of literature indicate reduced bone remodeling and altered bone microarchitecture. In corroboration, mean osteoblast proliferation was lower in patient samples when compared with those for normal osteoblasts obtained from age-matched, gender-matched donor organs (n = 5). Concentrations of 25-hydroxyvitamin-D3 correlated negatively with proteinuria and positively with osteoblast proliferation in culture
Laird, Eamon John. "Vitamin D status and metabolism : implications for bone health." Thesis, Ulster University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.674922.
Повний текст джерелаBall, Lindsay Clare. "Cystic fibrosis and vitamin D supplementation." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2010. https://www.mhsl.uab.edu/dt/2010m/ball.pdf.
Повний текст джерелаFinch, Sarah L. "Postnatal vitamin D supplementation normalizes neonatal bone mass following maternal dietary vitamin D deficiency in the guinea pig." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100246.
Повний текст джерелаEl, Fakhri Nagla. "Effect of vitamin D supplementation on bone status, glucose homeostasis and immune function in children with vitamin D deficiency." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7555/.
Повний текст джерелаSnellman, Greta. "Boning up on Vitamin D : Observational Studies on Bone and Health." Doctoral thesis, Uppsala universitet, Ortopedi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-159873.
Повний текст джерелаAnderson, Paul Hamill. "The regulation of Vitamin D metabolism in the kidney and bone." Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09pha5486.pdf.
Повний текст джерелаOutila, Terhi. "The effect of vitamin D status on calcium and bone metabolism." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/maa/skemi/vk/outila/.
Повний текст джерелаChen, Ketian. "Regulation of Human Bone Marrow-Derived Stem Cells by Hepatocyte Growth Factor." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/334.
Повний текст джерелаNaja, Roy Pascal. "The role of Vitamin D metabolic enzymes in bone development and repair /." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115860.
Повний текст джерелаThe CYP24A1 enzyme is involved in the catabolic breakdown of 1alpha,25-(OH)2D but also synthesizes the 24R,25-(OH) 2D metabolite. Studies in chicken suggest a role for 24R,25-(OH) 2D in fracture repair. We induced stabilized transverse mid-diaphysial fractures of the tibia in four-month-old wild-type and Cyp24a1-deficient mice. Examination of the callus sections showed delayed hard callus formation in the homozygous mutant animals compared to wild-type littermates. RT-qPCR showed perturbed levels of type X collagen transcripts in mutant mice at 14 and 21 days post-fracture, reflecting the delayed healing. Rescue of the impaired healing by subcutaneous injection of 24R,25-(OH)2D3 normalized the histological appearance of the callus, static histomorphometric index and type X collagen mRNA expression, while 1alpha,25-(OH)2D 3 did not. These results show that Cyp24a1 deficiency delays fracture repair and strongly suggest that vitamin D metabolites hydroxylated at position 24, such as 24R,25-(OH)2D, play an important role in the mechanisms leading to normal fracture healing.
Hamill, Matthew. "HIV, body composition, bone and vitamin D status in South African women." Thesis, University of Cambridge, 2013. https://www.repository.cam.ac.uk/handle/1810/270410.
Повний текст джерелаTOON, NICOLE MARIE. "INTAKES OF CALCIUM AND VITAMIN D AND THEIR RELATIONSHIP TO BONE HEALTH." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116019728.
Повний текст джерелаDrury, Donna. "Vitamin D and K status and bone health in pediatric cystic fibrosis patients." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101116.
Повний текст джерелаOur results showed poor bone mineral mass in these CF children despite mild disease and good nutritional status. Neither vitamin K nor D was a predictor of bone health but weight and height Z-scores, fat-free mass, physical activity and lung function were all consistent predictors.
These results indicate that nutritional status as well as physical activity are key determinants of bone health in CF children and offer a unique opportunity in the prevention of CF-related bone disease. Further vitamin intervention research needs to be done in this population.
Pollock, Catherine. "Novel aspects of vitamin D signalling in prostate cells." Thesis, University of Ulster, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.588498.
Повний текст джерелаDabbas, Basel. "Combined effects of vitamin D receptor agonists and histone deacetylase inhibition on vitamin D-resistant squamous carcinoma cells." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112395.
Повний текст джерелаKanan, Raed Mohammad. "Molecular genetics and biochemistry of vitamin D binding proteins in metabolic bone disease." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287811.
Повний текст джерелаHögström, Magnus. "Vitamins, fatty acids, physical activity and peak bone mass." Doctoral thesis, Umeå universitet, Kirurgisk och perioperativ vetenskap, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1451.
Повний текст джерелаPettersson, Filippa. "Retinoids and vitamin D analogues : effects on pancreatic adenocarcinoma cells." Thesis, St George's, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325810.
Повний текст джерелаWillett, Alexis Maria. "Factors affecting vitamin D status in older adolescents and their relevance to bone health." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615157.
Повний текст джерелаKhoja, Sawsan Omar. "Nutritional status of vitamin D and dietary intake of key bone health nutrients in Saudi Arabian women : implications for bone health." Thesis, University of Surrey, 2006. http://epubs.surrey.ac.uk/844240/.
Повний текст джерелаPronovost, Amy. "Vitamin D status and bone health in Inuit women 40 years of age and older." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86781.
Повний текст джерелаDes bas niveaux sériques de vitamine D (25(OH)D), un apport alimentaire insuffisant en calcium, ainsi qu'un risque élevé de fracture ont été rapportés séparément chez les femmes Inuit. Nous avons évalué le statut de vitamine D, l'apport alimentaire de nutriments, et la densité minérale osseuse à l'avant-bras (aDMO) chez les femmes Inuit (n=419, âgées de 40 à 90 ans) du Nunavut participant dans l'Enquête de Santé Inuit 2007/2008. Les taux sériques de 25(OH)D, d'ostéocalcine (OC) et de parathormone (PTH) ont été mesurés. Le statut de vitamine D était sous-optimal (≤ 75 nmol/L) dans chez 69.4% des femmes pré-ménopausées et 37.6% des femmes ménopausées. Les apports alimentaires de vitamine D et de calcium (par 1000 kcal) avaient tendance à augmenter avec l'âge. La aDMO était basse chez 33% des femmes ménopausées (T-score < -1.5) et 2% des femmes pré-ménopausées (Z-score < -2). Les prédicteurs de la aDMO comprenaient l'indice de masse corporelle et l'OC, ainsi que l'âge dans les femmes ménopausées et la PTH dans les femmes pré ménopausées. L'alimentation et le statut de vitamine D des femmes pré ménopausées suggèrent que, avec l'âge, leur risque pour l'ostéoporose sera plus élevé que la génération précédente.
Alyahya, Khulood Othman. "Extent of vitamin D deficiency in Kuwaiti adolescent females : implications for peak bone mass attainment." Thesis, University of Surrey, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499419.
Повний текст джерелаMaguire, Orla. "Novel chemo-protective roles of the Vitamin D Receptor in prostate cells." Thesis, University of Ulster, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529507.
Повний текст джерелаFeinglass, Erica A. "DESCRIPTIVE STUDY OF VITAMIN D STATUS AND CYSTIC FIBROSIS RELATED DIABETES." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429758063.
Повний текст джерелаHeitmann, Maximilian [Verfasser], Franz [Gutachter] Jakob, and Torsten [Gutachter] Blunk. "Vergleich der genetischen Eigenschaften von Bone Marrow derived Mesenchymal Stem Cells und Trabecular Bone derived Mesenchymal Stem Cells / Maximilian Heitmann. Gutachter: Franz Jakob ; Torsten Blunk." Würzburg : Universität Würzburg, 2015. http://d-nb.info/1103259474/34.
Повний текст джерелаSutton, Amelia L. "The Regulation and Function of 1,25-Dihydroxyvitamin D3-Induced Genes in Osteoblasts." Case Western Reserve University School of Graduate Studies / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1121820822.
Повний текст джерелаMilestone, Andrew Neill. "The immunomodulatory effects of vitamin D in Crohn's disease : dendritic cells, gamma delta T-cells and homing." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9904.
Повний текст джерелаNorton, Rosemary. "Effects of vitamin D on inflammation and oxidative stress in airway epithelial cells." Thesis, University of East Anglia, 2012. https://ueaeprints.uea.ac.uk/41410/.
Повний текст джерелаAl-Rahawi, Denise A. "Intakes of Calcium and Vitamin D and the Relationship to Bone Health: Incidence and Prevalence of Osteoporosis." Cincinnati, Ohio : University of Cincinnati, 2008. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1211920441.
Повний текст джерелаCommittee/Advisors: Shanil Juma PhD (Committee Chair), Hageman Gilbert PhD (Committee Member). Title from electronic thesis title page (viewed Aug.29, 2008). Includes abstract. Keywords: calcium and vitamin D; osteoporosis. Includes bibliographical references.
Grages, Monica B. "Relationships Between Serum Cortisol, Vitamin D, Bone Mineral Density, and Body Composition in National Team Figure Skaters." Digital Archive @ GSU, 2013. http://digitalarchive.gsu.edu/nutrition_theses/47.
Повний текст джерелаSilk, Leslie. "Calcium and Vitamin-D supplementation on bone structural properties in young male Jockeys: A randomised controlled trial." Thesis, Australian Catholic University, 2016. https://acuresearchbank.acu.edu.au/download/b38415a0b1630f712cff358878a59ed3b09ce195c9788c6e3b9ea5af70548166/8518493/Silk_2016_Calcium_and_vitamin_D_supplementation_on_bone_structural_properties_in_young_male_jockeys.pdf.
Повний текст джерелаHögström, Magnus. "Vitamins, fatty acids, physical activity and peak bone mass /." Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1451.
Повний текст джерелаNatarajan, Radhika. "Vitamin D metabolites inhibit adipocyte differentiation in ₃T₃-L₁ preadipocytes." Connect to this title, 2008. http://scholarworks.umass.edu/theses/164/.
Повний текст джерелаChristofyllakis, Konstantinos [Verfasser]. "Influence of Vitamin D on Genome-Wide Expression in Natural Killer Cells / Konstantinos Christofyllakis." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2021. http://d-nb.info/123367868X/34.
Повний текст джерелаLuco, Aimee-Lee. "Vitamin D strongly influences skeletal metastasis development in breast cancer: comparison of systemic vitamin D deficiency versus local ablation of CYP27B1 in breast tumour cells." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121223.
Повний текст джерелаLa vitamine D est bien connue pour son rôle dans le maintien des concentrations de calcium et du phosphore dans la circulation ainsi que dans la prévention du rachitisme. La découverte plus récente de sa capacité d'inhiber la prolifération cellulaire, induire leur différentiation ainsi que l'apoptose cellulaire, inhiber l'angiogenèse, et moduler le système immunitaire rend son étude un sujet de recherche très intéressant surtout dans le domaine de la recherche sur le cancer. Nous avons étudié l'effet de la carence en vitamine D sur la croissance tumorale dans un modèle murin de métastases osseuses du cancer du sein. Nous avons aussi établi que ces cellules expriment l'enzyme CYP27B1 (1α-hydroxylase) et sont donc capables d'activer la vitamine D en son métabolite actif la 1,25-dihydroxyvitamine D (1,25(OH)2D) à partir du métabolite inactif, la 25-hydroxyvitamine D (25(OH)D). Nous avons ensuite examiné l'effet de l'activation locale de la vitamine D par les cellules tumorales dérivées du sein sur la croissance de ces cellules dans le microenvironnement osseux. Nous n'avons constaté aucune différence significative entre la croissance des cellules tumorales du cancer du sein dans l'os chez les souris carencées en vitamine D en comparaison aux souris non carencées en vitamine D. Cependant, nous avons démontré que les cellules tumorales du cancer du sein qui expriment le CYP27B1 croissent beaucoup moins vite dans l'os que les cellules tumorales qui n'expriment pas le CYP27B1. Ces résultats suggèrent un rôle très important de l'activation extra-rénale de la vitamine D par les cellules tumorales du cancer du sein pour inhiber la croissance de ces cellules dans l'os. En conclusion, ces travaux indiquent que le précurseur inactif 25(OH)D pourrait être utilisé seul ou en combinaison pour le traitement des métastases osseuses du cancer du sein.
Vladeva, Valcheva Petya. "Role of vitamin D signalling in vascular smooth muscle cells - morphological and molecular study." Doctoral thesis, Universitat de Lleida, 2011. http://hdl.handle.net/10803/8286.
Повний текст джерела
La vitamina D ha estat durant molt de temps coneguda pel seu important paper en la
regulacio dels nivells de calci i fosfor, i en la mineralitzacio de l'os. Els efectes biologics de la
forma hormonalment activa de vitamina D (1,25(OH)2D3, o calcitriol) estan mediats per la
unio al receptor de vitamina D (VDR), que alhora actua sobre els elements de resposta
especifics (VDRE) en el promotor dels gens diana de vitamina D, modificant-ne l'expressio.
En les ultimes decades, s'ha demostrat que el VDR no solament es present en les dianes
classiques de la vitamina D com els ossos, els ronyons i l'intesti, sino tambe en molts altres
teixits, com els musculs esqueletics, llisos, i cardiacs, i tambe en el cervell, la pell i el fetge.
A mes del control de l'homeostasi mineral, la vitamina D exerceix accions pleiotropiques en
diferents tipus cel.lulars, influint en processos fisiologics importants com la proliferacio, la
diferenciacio cel.lular, la resposta immune, aixi com tambe en les diferents condicions
patologiques: el cancer, les malalties cardiovasculars, metaboliques i autoimmunes. A mes,
juntament amb els seus efectes endocrins, la vitamina D te funcions importants
autocrines/paracrines. En les cel.lules de muscul llis vascular (CMLV), la vitamina D regula la
proliferacio i la calcificacio, aquests dos processos, juntament amb la senescencia de les
CMLV es produeixen durant el proces aterosclerotic. Per poder-se dividir, les CMLV
necessiten l'energia de l'ATP produida per les mitocondries. Les alteracions de la funcio
mitocondrial estan relacionades amb una major produccio de radicals lliures. A la paret
arterial, l'angiotensina II (Ang II) actua com un potent mediador d'estres oxidatiu, provocant
senescencia prematura induida per l'estres (SIPS). Els nivells d'Ang II son controlats per la
renina, l'expressio de la qual es regulada per la vitamina D. Per tant, un defecte en la
senyalitzacio de la vitamina D pot conduir a un augment en els nivells d'Ang II i produir els
seus efectes adversos en la paret de l'arteria.
Quan es van cultivar les CMLV, obtingudes de ratolins knockout per VDR (VDRKO) es
va trobar un augment en la produccio d'Ang II en el medi de cultiu d'aquestes cel.lules en
comparacio amb el tipus salvatge (WT), que estava d'acord amb la major activacio del
sistema renina-angiotensina a nivell sistemic, que es va trobar en els ratolins mutants de
VDR. D'una banda, una disminucio en les taxes de proliferacio de les CMLV VDRKO es va
trobar in vitro i in vivo. Aquest descens va ser en paral.lel a un augment en el volum
cel.lular. En estat de repos, les cel.lules VDRKO presentaven un augment significatiu de
l'expressio de p57Kip2 juntament amb els nivells elevats de p19Arf, p21Cip1 i p27Kip1, i nivells
inferiors de PRB fosforilada, ciclines D i E, i axi es preve la seva proliferacio. A mes, les
cel.lules VDRKO van mostrar un augment en l'expressio de la catepsina D, un enzim amb
activitat com renina, i del receptor d'Ang II tipus 1. A mes, la produccio d'anio superoxid va
ser major en les cel.lules mutants, i va ser inhibida tant amb losartan com amb DPI. D'altra
banda, les cel.lules VDRKO presenten una disminucio significativa en l'expressio de l'enzim
mitocondrial antioxidant, la superoxid dismutasa de manganes (SOD2) i l'oxid nitric sintetasa
induible que produeix la molecula vasodilatadora NO,. Per respirometria d'alta resolucio es va
determinar que les mitocondries de VDRKO CMLV van ser menys eficients que podria explicar
el menor contingut d'ATP en aquestes cel.lules. Tots aquests factors es van relacionar amb el
fenotip senescent, que presentaven al voltant del 20% de les CMLV sense VDR en cultiu.
En conclusio, l'absencia de senyalitzacio per VDR en CMLV porta a SIPS causada per
l'augment en la produccio local d'Ang II, amb el conseguent augment dels radicals lliures,
produits per l'activacio de la NADPH oxidasa, el que suggereix un possible paper del sistema
de la vitamina D en malalties vasculars, que mostren una hiperproliferacio de les CMLV.
La vitamina D ha sido durante mucho tiempo conocida por su importante papel en la
regulacion de los niveles de calcio y fosforo, y en la mineralizacion del hueso. Los efectos
biologicos de la forma hormonalmente activa de la vitamina D (1,25(OH)2D3, o calcitriol)
estan mediados por la union al receptor de la vitamina D (VDR), que a su vez actua sobre los
elementos de respuesta a la vitamina D (VDRE) en el promotor de los genes diana,
modificando su expresion. En las ultimas decadas, se ha demostrado que el VDR esta
presente no solo en las dianas clasicas de la vitamina D, como los huesos, los rinones y el
intestino, sino tambien en muchos otros tejidos, como los musculos esqueleticos, lisos, y
cardiacos, y en el cerebro, la piel y el higado. Ademas del control de la homeostasis mineral,
la vitamina D ejerce acciones pleiotropicos en diferentes tipos celulares, influyendo en
procesos fisiologicos importantes tales como la proliferacion y diferenciacion celular, la
respuesta inmune, asi como diferentes condiciones patologicas como el cancer, las
enfermedades cardiovasculares, metabolicas y autoinmunes. Ademas, junto con sus efectos
endocrinos, la vitamina D tiene papeles autocrinas/paracrinas importantes. En las celulas de
musculo liso vascular (CMLV), la vitamina D regula la proliferacion y la calcificacion. Ambos
procesos, junto con la senescencia de las CMLV surgen durante el proceso aterosclerotico.
Para poder dividirse, las CMLV necesitan la energia del ATP producido por las mitocondrias.
Las alteraciones en la funcion mitocondrial estan relacionadas con una mayor produccion de
radicales libres. En la pared arterial, la angiotensina II (Ang II) actua como un potente
mediador de estres oxidativo, provocando senescencia prematura inducida por estres (SIPS).
Los niveles de Ang II son controlados por la renina, cuya expresion genica se regula por la
vitamina D. Por lo tanto, un defecto en la senalizacion de la vitamina D puede conducir a un
aumento en los niveles de Ang II y sus efectos adversos en la pared arterial.
Cuando se cultivaron CMLV, obtenidas de ratones knockout para VDR (VDRKO) se
encontro un aumento en la produccion de Ang II en el medio de cultivo de estas celulas,
comparando con el tipo salvaje (WT), lo que estaba de acuerdo con la mayor activacion de la
sistema renina-angiotensina a nivel sistemico, que fue encontrada en los ratones mutantes
de VDR. Por otra parte, una disminucion en la tasa de proliferacion de las VDRKO CMLV fue
encontrada in vitro e in vivo. Este descenso era en paralelo a un aumento en el volumen
celular. En estado de reposo, las celulas VDRKO presentaron un aumento significativo en la
expresion de p57Kip2 junto con niveles elevados de p19Arf, p21Cip1 y p27Kip1, y menores
niveles de pRb fosforilada y ciclinas D y E, asi previniendo su proliferacion. Ademas, las
celulas VDRKO mostraron un aumento en la expresion de la catepsina D, una enzima con
actividad parecida a la del renina, y del receptor de Ang II tipo 1. Ademas, la produccion del
anion superoxido fue mayor en las celulas mutantes, y fue inhibida tanto con losartan como
con DPI. Por otra parte, las celulas VDRKO presentaron una disminucion significativa en la
expresion de la enzima antioxidante mitocondrial superoxido dismutasa de manganeso
(SOD2) y la oxido nitrico sintetasa inducible, que produce la molecula vasodilatadora NO. Por
respirometria de alta resolucion fue determinado que las mitocondrias de las CMLV VDRKO
fueron menos eficientes que podria explicar el menor contenido de ATP en estas celulas.
Todos estos factores se relacionaron con el fenotipo senescente, presentado por alrededor de
20% de las CMLV que carecian VDR en cultivo.
En conclusion, la ausencia de senalizacion por VDR en CMLV lleva a SIPS debido al
aumento en la produccion local de Ang II, con el consiguiente aumento de los radicales
libres, producidos por la activacion de la NADPH oxidasa, lo que sugiere un posible papel del
sistema de la vitamina D en enfermedades vasculares, que muestran una hiperproliferacion
de las CMLV.
Vitamin D has long been known for its important role in regulating the levels
of calcium and phosphorus, and in mineralization of bone. The biological effects of
the hormonally active form of vitamin D (1,25(OH)2D3, or calcitriol) are mediated
by the binding to the vitamin D receptor (VDR) which in turn acts over specific
responsive elements (VDRE) in the promoter region of the vitamin D - target genes,
modifying their expression. In the last decades, it has been shown that VDR is
present not only in the classical vitamin D targets such as bone, kidney, and
intestine, but also in many other tissues, like skeletal, smooth, and heart muscles,
and in brain, skin, and liver. In addition to the control of the mineral homeostasis,
vitamin D exerts pleiotropic actions in a variety of cell types, influencing important
physiological processes such as cellular proliferation and differentiation, the
immune response as well as different pathological conditions like cancer,
cardiovascular, metabolic and autoimmune diseases. Moreover, together with its
endocrine effects, vitamin D has important autocrine/paracrine roles. In vascular
smooth muscle cells (VSMC), vitamin D regulates proliferation and calcification.
Both processes, together with VSMC senescence occur during the atherosclerotic
process. To be able to divide, VSMC need the energy of ATP produced by
mitochondria. Alterations in the mitochondrial function are related to increased
production of free radicals. In the artery wall, angiotensin II (Ang II) serves as a
potent mediator of oxidative stress, provoking stress-induced premature
senescence (SIPS). Ang II levels are controlled by renin, which gene expression is
regulated by vitamin D. Thus, a defect of vitamin D signalling could lead to an
increase in Ang II levels and its adverse effects in the artery wall.
When we cultured VSMC, obtained from VDR knockout (VDRKO) mice we
found an increment in the production of Ang II in the culture medium of these cells
in comparison with the wild type (WT), which was in accordance with the increased
activation of the renin-angiotensin system at systemic level, found in the VDR
mutant mice. Moreover, a decrease in the proliferation rates of VDRKO VSMC was
found in vitro and in vivo. This decrease was in parallel to an increase in the cell
volume. In quiescent state, VDRKO cells presented significantly increased
expression of p57Kip2 together with elevated levels of p19Arf, p21Cip1 and p27Kip1, and
lower levels of phosphorilated pRb and cyclins D and E, thus preventing their
proliferation. Furthermore, VDRKO cells showed an increase in the expression of
cathepsin D, an enzyme with renin-like activity, and of the Ang II receptor type 1.
Also, superoxide anion production was higher in the mutant cells, and was inhibited
with both, losartan and DPI. Moreover, the VDR ablated cells presented a significant
decrease in the expression of the mitochondrial antioxidant enzyme manganese
superoxide dismutase (SOD2) and the inducible nitric oxide synthase, which
produces the vasodilatator molecule NO. By high-resolution respirometry we found
that the mitochondria of VDRKO VSMC were less efficient which could explain the
lower content of ATP in these cells. All of these findings were associated with the
senescent phenotype, presented by around 20% of the VSMC lacking VDR in
culture.
In conclusion, the absence of VDR signalling in VSMC leads to SIPS due to the
increased local production of Ang II, with a subsequent increase in free radicals,
produced by the activation of the NADPH oxidase, which suggests a possible role of
the vitamin D system in vascular conditions which show hyperproliferation of VSMC.
McGregor, Reuben Hendrik Cameron. "Immunoregulatory effects of vitamin D and its mechanism of action in CD4+ T cells." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/immunoregulatory-effects-ofvitamin-d-and-its-mechanism-of-action-in-cd4-t-cells(c5b983f9-2a27-48ce-b1a6-89569416a82b).html.
Повний текст джерелаDoherty, Declan. "The Nuclear Vitamin D Receptor as a Mediator of Detoxofication Pathways in Enteric Cells." Thesis, University of Ulster, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529469.
Повний текст джерелаOmidi, Maryam [Verfasser], and Hartmut [Akademischer Betreuer] Schlüter. "Investigation of the Impact of Magnesium Implants on the Proteomes of Bone Cells and Bone Tissue / Maryam Omidi ; Betreuer: Hartmut Schlüter." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2017. http://d-nb.info/1137625023/34.
Повний текст джерелаKleinhans, Claudia [Verfasser], and Günter [Akademischer Betreuer] Tovar. "Evaluation of human bone and fat derived stem cells for their application in bone tissue engineering / Claudia Kleinhans. Betreuer: Günter Tovar." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2014. http://d-nb.info/1060047322/34.
Повний текст джерелаGarner, Caitlyn. "The Relationship Between Bone Mineral Density and Vitamin D, Calcium, and Iron Intake in Female Runners Across a Competitive Year." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1593017213203259.
Повний текст джерелаKELLY, MICHAEL ALAN. "CHARACTERIZATION OF RECEPTORS AND BINDING PROTEINS FOR THE ACTIVE METABOLITES OF VITAMINS A AND D IN NORMAL AND RESISTANT CELLS (PRIMATE RESEARCH)." Diss., The University of Arizona, 1986. http://hdl.handle.net/10150/183919.
Повний текст джерелаEspig, Sandy [Verfasser]. "Isolation and characterization of rat bone-marrow derived mesenchymal stromal cells / Sandy Espig." Ulm : Universität Ulm. Medizinische Fakultät, 2016. http://d-nb.info/1082294284/34.
Повний текст джерелаsharma, khushboo. "A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and vitamin D analogue, EB 1089." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3569.
Повний текст джерелаBell, Bryan Frederick. "Mechanisms regulating osteoblast response to surface microtopography and vitamin D." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/31711.
Повний текст джерелаCommittee Chair: Barbara Boyan; Committee Member: Andres Garcia; Committee Member: Anthony Norman; Committee Member: Nael McCarty; Committee Member: Zvi Schwartz. Part of the SMARTech Electronic Thesis and Dissertation Collection.