Person: Juarranz Moratilla, Yasmina
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First Name
Yasmina
Last Name
Juarranz Moratilla
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Biología Celular
Area
Biología Celular
Identifiers
35 results
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Item Vasoactive intestinal peptide exerts an osteoinductive effect in human mesenchymal stem cells(BioFactors, 2024) Castro Vázquez, David; Arribas Castaño, Paula; García López, Iván; Gutiérrez Cañas, Irene; Pérez García, Selene; Lamana Domínguez, Amalia; Villanueva Romero, Raúl; Cabrera Martín, Alicia; Tecza , Karolina; Martínez Mora, María Del Carmen; Juarranz Moratilla, Yasmina; Pérez Gomáriz, Rosa María; Carrión Caballo, MarSeveral neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine-tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis.Item Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast‐derived ADAMTS‐7 and ‐12(Journal of Cellular and Molecular Medicine, 2019) Pérez García, Selene; Carrión Caballo, Mar; Villanueva Romero, Raúl; Hermida Gómez, Tamara; Fernández Moreno, Mercedes; Mellado, Mario; Blanco, Francisco J.; Juarranz Moratilla, Yasmina; Gomáriz, Rosa P.Failure of therapeutic approaches for the treatment of osteoarthritis (OA) based on the inhibition of metalloproteinases, might be because of their constitutive expres‐ sion in homeostasis, together with their network complexity. The knowledge of this network would contribute to selective target pathological conditions. In this sense, blockade of mediators produced by neighbouring joint cells, such as synovial fibro‐ blasts (SF), would prevent cartilage damage. Thus, we studied the contribution of ADAMTS‐7 and ‐12 from SF to cartilage oligomeric matrix protein (COMP) degrada‐ tion, and the signalling pathways involved in their expression. We report for the first time in SF, the involvement of ERK‐Runx2 axis and Wnt/β‐catenin signalling in ADAMTS‐12 and ADAMTS‐7 expressions, respectively, with the subsequent conse‐ quences in COMP degradation from cartilage extracellular matrix. After stimulation with IL‐1β or fibronectin fragments, we showed that ERK inhibition decreased Runx2 activation and ADAMTS‐12 expression in OA‐SF, also reducing Fn‐fs‐induced COMP degradation. Blockage of Wnt signalling by DKK1 reduced ADAMTS‐7 and COMP degradation in OA‐SF as well. In addition, Wnt7B expression was induced by IL‐1β and by itself, also increasing ADAMTS‐7. Our results could contribute to the develop‐ ment of disease‐modifying OA drugs targeting ADAMTS‐7 and ‐12 for the prevention of extracellular matrix components degradation like COMP.Item VIP and CRF reduce ADAMTS expression and function in osteoarthritis synovial fibroblasts(Journal of cellular and molecular medicine, 2016) Pérez García, Selene; Carrión Caballo, Mar; Gutiérrez Cañas, Irene; González Álvaro, Isidoro; Pérez Gomáriz, Rosa María; Juarranz Moratilla, YasminaADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family is known to play an important role in the pathogenesis of osteoarthritis (OA), working on aggrecan degradation or altering the integrity of extracellular matrix (ECM). Thus, the main purpose of our study was to define the role of vasoactive intestinal peptide (VIP) and corticotrophin-releasing factor (CRF), as immunoregulatory neuropeptides, on ADAMTS production in synovial fibroblasts (SF) from OA patients and healthy donors (HD). OA- and HD-SF were stimulated with pro-inflammatory mediators and treated with VIP or CRF. Both neuropeptides decreased ADAMTS-4, -5, -7 and -12 expressions, aggrecanase activity,glycosaminoglycans (GAG), and cartilage oligomeric matrix protein (COMP) degradation after stimulation with fibronectin fragments (Fn-fs) in OA-SF. After stimulation with interleukin-1b, VIP reduced ADAMTS-4 and -5, and both neuropeptides decreased ADAMTS-7 production and COMP degradation. Moreover, VIP and CRF reduced Runx2 and b-catenin activation in OA-SF. Our data suggest that the role of VIP and CRF on ADAMTS expression and cartilage degradation could be related to the OA pathology since scarce effects were produced in HD-SF. In addition,their effects might be greater when a degradation loop has been established, given that they were higher after stimulation with Fn-fs. Our results point to novel OA therapies based on the use of neuropeptides, since VIP and CRF are able to stop the first critical step, the loss of cartilageaggrecan and the ECM destabilization during joint degradationItem Mapping the CRF-urocortins system in human osteoarthritic and rheumatoid synovial fibroblasts: Effect of vasoactive intestinal peptide(2011) Pérez García, Selene; Juarranz Moratilla, Yasmina; Carrión Caballo, Mar; Gutiérrez Cañas, Irene; Margioris, Andrew; Pablos Álvarez, José Luis; Tsatsanis, Christos; Pérez Gomáriz, Rosa MaríaIn addition to the brain and pituitary gland, the corticotrophin-releasing factor (CRF) system is expressed in peripheral tissues. In this study we characterize the expression of CRF, urocortins (UCN1, UCN2, and UCN3), and their receptors (CRFR1 and CRFR2) in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Moreover, we analyze the vasoactive intestinal peptide (VIP) effect on the CRF system, as well as its physiological consequences on mediators of inflammatory/destructive processes. CRF and UCNs exhibit differential pattern in OA and RA-FLS. By real-time PCR we detected more expression of CRF and UCN1 in RA, and UCN2 and UCN3 in OA, while the CRFR2 expression was similar. In RA-FLS VIP treatment resulted in a significant decrease of the proinflammatory peptides, CRF and UCN1, and a significant increase of the potential anti-inflammatory agents, UCN3 and CRFR2. Using Western blot assays, we showed that the ratio between phospho-CREB (p-CREB) and c-AMP response element-binding (CREB) is higher in OA and significantly lower in RA-FLS after VIP treatment, with consequences upon cAMP response element in CRF and UCN1 genes. Real-time PCR and EIA proved that VIP significantly inhibits cycloxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in RA-FLS. In all cases, we consider significant data when P<0.05. These data indicate a role of endogenous CRF, UCNs, and CRFR2 in the OA and RA joint microenvironment. We confirm the anti-inflammatory function of VIP, through the modulation of the expression of CRF system that impacts in a reduction of mediators with inflammatory/destructive functions, supporting its therapeutic potential in rheumatic diseases.Item Activation of Th lymphocytes alters pattern expression and cellular location of VIP receptors in healthy donors and early arthritis patients(Scientific Reports, 2019) Villanueva Romero, Raúl; Gutiérrez Cañas, Irene; Carrión Caballo, Mar; González Álvaro, Isidoro; Rodríguez Frade, José Miguel; Mellado, Mario; Martínez, Carmen; Gomáriz, Rosa P.; Juarranz Moratilla, YasminaVasoactive Intestinal Peptide (VIP) is an important immunomodulator of CD4+ cells in normal and pathological conditions, which exerts its anti-infammatory and immunomodulatory actions through VPAC receptors, VPAC1 and VPAC2. Only a decrease in the expression of VPAC1 mRNA on Th cells upon activation has been reported. Thus, the deepening in the knowledge of the behavior of these receptors may contribute to the design of new therapies based on their activation and/or blockade. In this study, we describe the expression pattern, cellular location and functional role of VIP receptors during the activation of human Th cells in healthy conditions and in early arthritis (EA). The protein expression pattern of VPAC1 did not change with the activation of Th lymphocytes, whereas VPAC2 was up-regulated. In resting cells, VPAC1 was located on the plasma membrane and nucleus, whereas it only appeared in the nucleus in activated cells. VPAC2 was always found in plasma membrane location. VIP receptors signaled through a PKA-dependent pathway in both conditions, and also by a PKAindependent pathway in activated cells. Both receptors exhibit a potent immunomodulatory capacity by controlling the pathogenic profle and the activation markers of Th cells. These results highlight a novel translational view in infammatory/autoimmune diseases.Item Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12(American Journal of Pathology, 2016) Pérez García, Selene; Gutiérrez Cañas, Irene; Seoane Valiño, Iria V.; Fernández, Julián; Mellado, Mario; Leceta Martínez, Javier; Tío, Laura; Villanueva Romero, Raúl; Juarranz Moratilla, Yasmina; Pérez Gomáriz, Rosa MaríaCurrent description of osteoarthritis includes the involvement of synovial inflammation. Studies contributing to understanding the mechanisms of cross-talk and feedback among the joint tissues could be relevant to the development of therapies that block disease progression. During osteoarthritis, synovial fibroblasts exposed to anomalous mechanical forces and an inflammatory microenvironment release factors such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) metalloproteinases that mediate tissue damage and perpetuate inflammation. We therefore studied the production of ADAMTS by synovial fibroblasts and their contribution to cartilage degradation. Moreover, we analyzed the implication of two mediators present in the osteoarthritis joint, IL-1β as proinflammatory cytokine, and 45-kDa fibronectin fragments as products of matrix degradation. We reported that synovial fibroblasts constitutively express and release ADAMTS 4, 5, 7, and 12. Despite the contribution of both mediators to the stimulation of Runx2 and Wnt/β-catenin signaling pathways, as well as to ADAMTS expression, promoting the degradation of aggrecan and cartilage oligomeric matrix protein from cartilage, fibronectin fragments rather than IL-1β played the major pathological role in osteoarthritis,contributing to the maintenance of the disease. Moreover, higher levels of ADAMTS 4 and 7 and a specific regulation of ADAMTS-12 were observed in osteoarthritis, suggesting them as new potential therapeutic targets. Therefore, synovial fibroblasts provide the biochemical tools to the chronicity and destruction of the osteoarthritic joints.Item The Neuropeptide VIP Limits Human Osteoclastogenesis: Clinical Associations with Bone Metabolism Markers in Patients with Early Arthritis(Biomedicines, 2021) Castro Vázquez, David; Lamana, Amalia; Arribas Castaño, Paula; Gutiérrez Cañas, Irene; Villanueva Romero, Raúl; Pérez García, Selene; Martínez Mora, Carmen; Juarranz Moratilla, Yasmina; Fernández de Córdoba, Sara; González Álvaro, Isidoro; Gomáriz, Rosa P.; Carrión Caballo, MarWe aimed to evaluate the direct action of VIP on crucial molecules involved in human osteoclast differentiation and function. We also investigated the relationship between VIP serum levels and bone remodeling mediators in early arthritis patients. The expression of VIP receptors and osteoclast gene markers in monocytes and in vitro differentiated osteoclasts was studied by real-time PCR. NFATc1 activity was measured using a TransAM® kit. Osteoclastogenesis was confirmed by quantification of tartrate-resistant acid phosphatase positive multinucleated cells. OsteoAssay® Surface Multiple Well Plate was used to evaluate bone-resorbing activity. The ring-shaped actin cytoskeleton and the VPAC1 and VPAC2 expression were analyzed by immunofluorescence. We described the presence of VIP receptors in monocytes and mature osteoclasts. Osteoclasts that formed in the presence of VIP showed a decreased expression of osteoclast differentiation gene markers and proteolytic enzymes involved in bone resorption. VIP reduced the resorption activity and decreased both β3 integrin expression and actin ring formation. Elevated serum VIP levels in early arthritis patients were associated with lower BMD loss and higher serum OPG concentration. These results demonstrate that VIP exerts an anti-osteoclastogenic action impairing both differentiation and resorption activity mainly through the negative regulation of NFATc1, evidencing its bone-protective effects in humans.- Project number: 208
Item Aplicación de la clase invertida en la asignatura Biología Celular e Histología(2020) Gutiérrez Cañas, Irene; Carrión Caballo, Mar; Juarranz Moratilla, Yasmina; Lamana Domínguez, Amalia; López Redondo, Jesús María; Morona Arribas, Ruth; Muñoz Céspedes, Alberto; Ortega Moreno, Álvaro Dario; Pérez García, Selene; Pérez Gomariz, Rosa MaríaLa clase invertida o clase al revés, también conocida por el anglicismo flipped classroom, es una metodología docente en la que, como su nombre indica, se invierten los procesos que clásicamente tienen lugar dentro y fuera del aula. De manera que se pasa de una clase centrada en el profesor, como transmisor de la información y con un alumno receptor pasivo de la información cuyo trabajo fuera del aula consiste en la realización de tareas, a un modelo en el que el alumno, debe recibir y asimilar la información que le es facilitada previamente a la clase. En el aula, los alumnos resuelven dudas y realizan tareas, en muchos casos en equipo, de manera que el trabajo en el aula pasa a estar centrado en el alumno, que debe ser responsable de su propio aprendizaje. Los profesores que ya aplican esta metodología en distintos niveles educativos, se muestran muy satisfechos con el aumento del rendimiento de los estudiantes, la gran aceptación que tiene esta metodología, el aumento del aprendizaje significativo, es decir, la capacidad de relacionar los conocimientos previos con los nuevos y ser capaces de aplicar lo aprendido para la resolución de problemas. La asignatura “Biología Celular e Histología” del Grado en Biología se imparte con carácter anual durante el primer curso del grado, con una carga docente de 12 ECTS. Cada año se matriculan en la asignatura más de 400 alumnos, 300 en primera matrícula. Los contenidos teóricos que deben adquirir los alumnos son extensos y complejos, lo que supone una notable carga de trabajo para los alumnos que, si se limitan a una mera asistencia pasiva a clase, no son capaces de obtener un aprovechamiento óptimo de los contenidos y por tanto obtener buenos resultados. Además de esos contenidos teóricos, los alumnos deben adquirir unos contenidos prácticos mediante 5 sesiones de laboratorio de Biología Celular y 9 sesiones de laboratorio de Histología. Existen varios profesores implicados en la docencia teórica de esta asignatura, ya que los alumnos matriculados se dividen en 6 grupos y en algunos casos, la docencia se divide entre dos profesores, uno encargado de la parte de Biología Celular y otro de la parte de Histología. Cada profesor tiene su propio perfil docente, pero todos basamos nuestras clases en una metodología tradicional de clase magistral, es decir, una docencia centrada en el profesor, como foco transmisor de información que el alumno debe asimilar. Todos utilizamos el Campus Virtual donde colocamos las presentaciones que utilizamos en clase y donde organizamos las sesiones de seminarios. En general, año tras año, los profesores de esta asignatura observamos una falta de implicación de los alumnos en su propio aprendizaje, de manera que reciben la información de manera pasiva, escuchando al profesor, en muchos casos sin ni siquiera tomar apuntes. Esta pasividad y escasa implicación del alumnado conlleva unos resultados reflejados en las calificaciones globales generalmente decepcionantes, y que a nuestro juicio son susceptibles de mejora aumentando la motivación del alumnado mediante nuevas metodologías docentes. Con este proyecto de innovación docente, hemos elaborado el material necesario para aplicar el método “flipped learning” o clase invertida en un bloque de temas de Biología Celular y en otro bloque de temas de Histología. Este tipo de metodología centrada en el alumno, permite que el estudiante procese y maneje la información suministrada de forma autónoma, antes de acudir a clase, a su ritmo, de manera que el tiempo de clase puede usarse de otras maneras, por ejemplo, para solucionar dudas, discutir a fondo los aspectos más complicados del tema, o para realizar tareas de aplicación de los conocimientos previamente aprendidos en casa. De esta manera se puede lograr un aprendizaje significativo alejado de la mera memorización de los contenidos expuestos, y en donde el alumno se sienta protagonista de su propio avance y capacitación teórica de la asignatura. Item Inhibitory Role of Growth Hormone in the Induction and Progression Phases of Collagen-Induced Arthritis(Frontiers in immunology, 2018) Villares, Ricardo; Criado, Gabriel; Juarranz Moratilla, Yasmina; López Santalla, Mercedes; García-Cuesta, Eva María; Rodríguez Frade, José Miguel; Leceta Martínez, Javier; Lucas, Pilar; Pablos, José L.; Martínez-A., Carlos; Garín, Marina I.; Gomáriz, Rosa P.; Mellado, MarioEvidence indicates an intimate connection between the neuroendocrine and the immune systems. A number of in vitro and in vivo studies have demonstrated growth hormone (GH) involvement in immune regulation. The GH receptor is expressed by several leukocyte subpopulations, and GH modulates immune cell proliferation and activity. Here, we found that sustained GH expression protected against collagen-induced arthritis (CIA); in GH-transgenic C57BL/6 (GHTg) mice, disease onset was delayed, and its overall severity was decreased. The anti-collagen response was impaired in these mice, as were inflammatory cytokine levels. Compared to control arthritic littermates, immunized GHTg mice showed significantly lower RORγt (retinoic acid receptor-related orphan receptor gamma 2), IL-17, GM-CSF, IL-22, and IFNγ mRNA expression in draining lymph nodes, whereas there were no differences in IL-21, IL-6, or IL-2 mRNA levels. Data thus suggest that Th17/Th1 cell plasticity toward a pathological phenotype is reduced in these mice. Exogenous GH administration in arthritic DBA/1J mice reduced the severity of established CIA as well as the inflammatory environment, which also shows a GH effect on arthritis progression. These results indicate that GH prevents inflammatory joint destruction in CIA. Our findings demonstrate a modulatory GH role in immune system function that contributes to alleviating CIA symptoms and underlines the importance of endocrine regulation of the immune response.Item Memoria de investigación 2017-2018 : Departamento de Biología Celular (Universidad Complutense de Madrid)(2019) Juarranz Moratilla, YasminaMemoria anual del Departamento de Biología Celular de la UCM, correspondiente al curso 2017-2018. Recopila la documentación sobre grupos de investigación UCM, la relación de integrantes del Departamento, y el listado de publicaciones, congresos, tesis doctorales y otros trabajos académicos dirigidos, proyectos I+D+i, personal contratado con cargo a proyectos, estancias en centros nacionales e internacionales, conferencias impartidas, etc.