Evaluación de la presencia y regulación de canales de potencial transitorio en células similares a odontoblastos y su posible uso en el control de la sensibilidad y el dolor dental

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dc.contributor.advisorCastellanos Parra, Jaime Eduardo
dc.contributor.advisorVelandia-Romero, Myriam Lucia
dc.contributor.authorBernal Cepeda, Lilia Jadith
dc.contributor.cvlachttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000923982spa
dc.contributor.googlescholarhttps://scholar.google.com/citations?hl=es&user=0OO2U0EAAAAJspa
dc.contributor.orcid0000-0002-2889-5497spa
dc.contributor.researchgatehttps://www.researchgate.net/profile/Lilia-Bernal-Cepedaspa
dc.contributor.researchgroupGrupo de Investigación Básica y Aplicada en Odontologíaspa
dc.contributor.scopus57219538989spa
dc.date.accessioned2025-04-08T14:46:02Z
dc.date.available2025-04-08T14:46:02Z
dc.date.issued2025
dc.descriptionilustraciones, diagramasspa
dc.description.abstractEl dolor y la hipersensibilidad dental son condiciones prevalentes que constituyen desafíos clínicos constantes y a pesar de las estrategias terapéuticas disponibles, su eficacia es limitada. En la fisiopatología del dolor dental se ha descrito que los odontoblastos participan en la transducción de diferentes estímulos a través de la expresión de receptores transmembranales, incluyendo canales de potencial transitorio-TRP-, por esta razón el objetivo de este trabajo fue evaluar la expresión, modulación y respuesta farmacológica de algunos canales TRP en células humanas similares a odontoblastos-OLCs-, considerándolos como potenciales blancos farmacológicos para el manejo del dolor y la hipersensibilidad dental. Se identificaron transcritos para algunos canales TRP y se confirmó la expresión de TRPA1, TRPM8, TRPV1 y TRPV4 mediante inmunofluorescencia, canales relacionados con procesos de dolor nociceptivo y neuropático. Su activación se evaluó empleando el indicador Fluo-4 AM, y agonistas/antagonistas, encontrándose un [Ca2+]i -F/F0- de 1,97±0,25, 2,14±0,26, 2,67±0,10 y 1,46+0,09, respectivamente. Los desafíos térmicos e hiperosmóticos, resultan de intereses por su relación con la inducción de dolor dental; la estimulación con 45°C indujo un aumento de dos veces el valor de F/F0 (4,3±0,28) en comparación con el estímulo de 15°C (2,1±0,7). Sin embargo, los estímulos hiperosmóticos de manitol y xilitol generaron valores F/F0 comparables (4,41±0,42 y 4,51±0,41). Esto sugiriere que los estímulos térmicos e hiperosmóticos inducen la activación de los canales TRP evaluados en los OLCs. Luego de determinar la activación de TRPV1, se encontró un incrementó en la fosforilación de AKT, PRAS 40, Src, ERK, JNK, p38α, algunas proteínas STAT y β-Catenina, indicando que múltiples vías pueden estar involucradas en el proceso de sensibilización de TRPV1. Finalmente, se elaboraron hidrogeles particulados cargados con Capsazepina biocompatibles y biodegradables, y con la capacidad de liberar el activo por un período prolongado, logrando modular la actividad de TRPV1. Este trabajo mostró que la modulación farmacológica de los canales TRP modifica la respuesta en OLCs, lo cual abre posibilidades para el desarrollo de tratamientos más específicos y efectivos para el dolor y la hipersensibilidad dental (Texto tomado de la fuente)spa
dc.description.abstractDental pain and hypersensitivity are prevalent conditions that constitute clinical challenges. Although therapeutic strategies are available, their effectiveness in treating these conditions is limited. During the pathophysiology of dental pain, odontoblasts are responsible for transducing different stimuli that lead to the expression of transmembrane receptors, including transient receptor potential (TRP) channels. This work aimed to evaluate the expression, modulation, and pharmacological response of some TRP channels in human odontoblast-like cells (OLCs), considering them as potential pharmacological targets for the management of pain and dental hypersensitivity. We identified transcripts corresponding to TRP channels. Using immunofluorescence, we further identified and confirmed the expression of TRPV4, TRPA1, TRPM8, and TRPV1, which are channels related to nociceptive and neuropathic pain processes. We next evaluated the activation of these channels using the Fluo-4 AM indicator in the presence of agonists/antagonists. We found that F/F0 ratio of intracellular Ca was more sensitive in the case of TRPV1 relative to the others (2,67±0,10 versus 1,46±0,09, 1,97±0,25, 2,14±0,26). Thermal and hyperosmotic challenges are of interest due to their relationship with the induction of dental pain. Notably, culturing odontoblast-like cells at 45°C yielded two-fold increase in F/F0 values (4,3±0,28) compared to culturing conditions of 15°C (2,1±0,7). Moreover, the hyperosmotic stimuli of mannitol and xylitol generated comparable F/F0 ratio (4,41±0,42 and 4,51±0,41). These findings suggest that thermal and hyperosmotic stimuli activate TRP channels in OLCs. Following TRPV1 activation by temperature or hyperosmotic stimuli, we observed increased phosphorylation of multiple signaling proteins including AKT, PRAS40, Src, ERK, JNK, p38α, certain STAT proteins, and β-Catenin, indicating involvement of multiple pathways in TRPV1 sensitization. Finally, we developed biocompatible and biodegradable hydrogels loaded with Capsazepine, with the capacity to release the active agent over a prolonged period, modulating the activity of TRPV1. This work showed that the pharmacological modulation of TRP channels alters the response in OLCs, opening up possibilities for the development of more specific and effective treatments for dental pain and hypersensitivity.eng
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Ciencias-Farmacéuticasspa
dc.description.researchareaFarmacología Experimentalspa
dc.format.extentxvii, 208 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/87888
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Doctorado en Ciencias Farmacéuticasspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial 4.0 Internacionalspa
dc.subject.ddc610 - Medicina y salud::617 - Cirugía, medicina regional, odontología, oftalmología, otología, audiologíaspa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.lembDenticiónspa
dc.subject.lembDentitioneng
dc.subject.lembOdontalgiaeng
dc.subject.proposalCanales TRPspa
dc.subject.proposalTRPV1spa
dc.subject.proposalOdontoblastosspa
dc.subject.proposalDolor dentalspa
dc.subject.proposalHipersensibilidad dentalspa
dc.subject.proposalHidrogelesspa
dc.subject.proposalTRP channelseng
dc.subject.proposalTRPV1eng
dc.subject.proposalOdontoblastseng
dc.subject.proposalDental paineng
dc.subject.proposalDental hypersensitivityeng
dc.subject.proposalHydrogelseng
dc.subject.wikidataOdontoblastospa
dc.titleEvaluación de la presencia y regulación de canales de potencial transitorio en células similares a odontoblastos y su posible uso en el control de la sensibilidad y el dolor dentalspa
dc.title.translatedEvaluation of the expression and regulation of transient potential channels in odontoblast-like cells and their possible use in the control of dental sensitivity and paineng
dc.typeTrabajo de grado - Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06spa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
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dc.type.driverinfo:eu-repo/semantics/doctoralThesisspa
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dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
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dcterms.audience.professionaldevelopmentPersonal de apoyo escolarspa
dcterms.audience.professionaldevelopmentPúblico generalspa
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