Expresión del receptor TRPV1 en celulas similares a odontoblastos humanos: una alternativa terapéutica para el dolor y la sensibilidad dentinal

dc.contributor.advisorBaldión Elorza, Paula Alejandraspa
dc.contributor.authorLatorre Mora, Karen Lorenaspa
dc.contributor.researchgroupInvestigación Básica y Aplicada en Odontologíaspa
dc.date.accessioned2021-02-09T16:38:05Zspa
dc.date.available2021-02-09T16:38:05Zspa
dc.date.issued2020-08-18spa
dc.description.abstractDentin hypersensitivity and dental pain are a frequent reason for consultation in dentistry; however, its pathophysiology has not yet been fully clarified. Previous findings have made it possible to relate the cellular sensory capacity with the activation of the polymodal receptor TRPV1, responsible for the nociceptive response and whose desensitization could cause analgesia. For this reason, the objective of this was to determine the expression, localization and functional activity of TRPV1 in human odontoblast-like cells (hOLCs). The human dental pulp stem cells (hDPSCs) were obtained and characterized and subjected to odontogenic differentiation for 7, 14 and 21 days; and its phenotype was evaluated by immunofluorescence for the odontogenic markers dentinal matrix protein 1 (DMP-1) and dentin sialoprotein (DSP). TRPV1 gene expression was estimated by RT-qPCR and its location was established by immunofluorescence. The EC50 of Eugenol (EUG) and Capsaicin (CAP) was determined and the activation of the receptor was evaluated under chemical, thermal and under changes in pH stimulation. For the statistical analysis, a oneway ANOVA was used with a Tukey post hoc test (p <0.05). After establishing the expression and membrane localization of TRPV1 in hOLCs, its chemical activation with EUG and CAP, its thermal at ≥ 43 °C and its activation with acidic pH <6 or basic ―between 9 and 12― were demonstrated. Receptor desensitization was achieved after 20 min exposure to concentrations of 603.5 and 1000 µM of EUG. These findings represent a contribution to the construction of a pulp pain study model aimed at offering therapeutic alternatives for these pathologies.spa
dc.description.abstractLa hipersensibilidad dentinal y el dolor dental son motivo de consulta frecuente en odontología; sin embargo, aún no se ha esclarecido totalmente su fisiopatología. Hallazgos previos han permitido relacionar la capacidad sensitiva celular con la activación del receptor polimodal TRPV1, responsable de la respuesta nociceptiva y cuya desensibilización podría provocar analgesia. Por esta razón, el objetivo de este estudio fue determinar la expresión, localización y actividad funcional de TRPV1 en células similares a odontoblastos humanos (hOLCs). Se obtuvieron células madre mesenquimales (hDPSCs) que fueron caracterizadas y sometidas a diferenciación odontogénica por 7, 14 y 21 días; y se evaluó su fenotipo mediante inmunofluorescencia para los marcadores odontogénicos proteína de matriz dentinal 1 (DMP-1) y sialoproteína dentinal (DSP). Se estimó la expresión génica de TRPV1 mediante RT-qPCR y la localización del mismo se estableció mediante inmunofluorescencia. Se determinó la CE50 de Eugenol (EUG) y Capsaicina (CAP) y se evaluó la activación del receptor ante estimulación química, térmica y bajo exposición a distintos pH. Para el análisis estadístico se utilizó un ANOVA de una vía con una prueba post hoc de Tukey (p<0.05). Tras establecer en hOLCs la expresión y localización membranal de TRPV1, se demostró su activación química con EUG y CAP, su activación térmica a ≥ 43 °C, y su activación con pH ácidos <6 o básicos ―entre 9 y 12―. La desensibilización del receptor se logró tras una exposición de 20 min a concentraciones de 603,5 y 1000 μM de EUG. Estos hallazgos representan un aporte para la construcción de un modelo de estudio del dolor pulpar orientado a ofrecer alternativas terapéuticas para estas patologías.spa
dc.description.additionalLínea de Investigación: Medicina Oral.spa
dc.description.degreelevelMaestríaspa
dc.description.projectEXPRESION DEL RECEPTOR DE DOLOR TRPV1 EN ODONTOBLASTOS HUMANOS INMORTALIZADOSspa
dc.description.sponsorshipConvocatoria para el fortalecimiento de alianzas interdisciplinarias y creación artística de la sede Bogotá de la Universidad Nacional de Colombia, 2018spa
dc.format.extent88spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.citationLatorre Mora, K. L. (2020). Expresión del receptor TRPV1 en celulas similares a odontoblastos humanos: una alternativa terapéutica para el dolor y la sensibilidad dentinal [Tesis de maestría, Universidad Nacional de Colombia]. Repositorio Institucional.spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/79164
dc.language.isospaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Farmaciaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Farmacologíaspa
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dc.relation.referencesZhang, F., Jara-oseguera, A., Chang, T., Bae, C., Hanson, S. M., & Swartz, K. J. (2017). Heat activation is intrinsic to the pore domain of TRPV1. PNAS, 317–324. https://doi.org/10.1073/pnas.1717192115spa
dc.relation.referencesJung, J., Shin, J. S., Lee, S., Hwang, S. W., Koo, J., Cho, H., & Oh, U. (2004). Phosphorylation of Vanilloid Receptor 1 by Ca 2 / Calmodulin- dependent Kinase II Regulates Its Vanilloid Binding. The Journal of Biological Chemistry, 279(8), 7048– 7054. https://doi.org/10.1074/jbc.M311448200spa
dc.relation.referencesSanz-salvador, L., Andres-borderia, A., Ferrer-montiel, A., & Planells-cases, R. (2012).Agonist- and Ca 2 -dependent Desensitization of TRPV1 Channel Targets the Receptor to Lysosomes for. The Journal of Biological Chemistry, 287(23), 19462–19471. https://doi.org/10.1074/jbc.M111.289751spa
dc.relation.referencesMohapatra, Durga Prasanna, & Nau, C. (2005). Regulation of Ca 2 -dependent Desensitization in the Vanilloid Receptor TRPV1 by Calcineurin and cAMP dependent Protein Kinase *. The Journal of Biological Chemistry, 280(14), 13424– 13432. https://doi.org/10.1074/jbc.M410917200spa
dc.relation.referencesMinisterio de Salud y Protección Social. (2014). IV Estudio Nacional de Salud BucalENSAB. https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ENSAB-IVSituacion-Bucal-Actual.pdfspa
dc.rightsDerechos reservados - Universidad Nacional de Colombiaspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.spaAcceso abiertospa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.ddc615 - Farmacología y terapéuticaspa
dc.subject.proposalOdontoblastseng
dc.subject.proposalOdontoblastospa
dc.subject.proposalHipersensibilidad dentinalspa
dc.subject.proposalToothacheeng
dc.subject.proposalReceptor TRPV1spa
dc.subject.proposalTRPV1 cation channelseng
dc.subject.proposalReceptor TRPspa
dc.subject.proposalTRPV1 receptoreng
dc.subject.proposalTransiet receptor ponential channeleng
dc.titleExpresión del receptor TRPV1 en celulas similares a odontoblastos humanos: una alternativa terapéutica para el dolor y la sensibilidad dentinalspa
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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