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dc.contributor.authorGuerrero Pavón, Fátima
dc.contributor.authorHerencia, Carmen
dc.contributor.authorAlmadén Peña, Yolanda
dc.contributor.authorMartínez-Moreno, Julio M.
dc.contributor.authorMontes de Oca, Addy
dc.contributor.authorRodríguez-Ortiz, Maria E.
dc.contributor.authorDíaz Tocados, Juan Manuel
dc.contributor.authorFlorio, Mónica
dc.contributor.authorLópez, Ignacio
dc.contributor.authorRichards, William G.
dc.contributor.authorRodríguez Portillo, Mariano
dc.contributor.authorAguilera Tejero, Escolástico
dc.contributor.authorMuñoz-Castañeda, Juan R.
dc.date.accessioned2017-11-23T10:53:00Z
dc.date.available2017-11-23T10:53:00Z
dc.date.issued2014
dc.identifier.urihttp://hdl.handle.net/10396/15501
dc.description.abstractBackground: Transforming growth factor-b (TGF-b) is a key cytokine during differentiation of mesenchymal stem cells (MSC) into vascular smooth muscle cells (VSMC). High phosphate induces a phenotypic transformation of vascular smooth muscle cells (VSMC) into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMC differentiation of MSC in presence or not of high phosphate. Results: Our results showed that TGF-b induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22a, myocardin, and smooth muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/bcatenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-b to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-b pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition of both Wnt/b-catenin activators CHIR98014 and lithium chloride enhanced the effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase activity. Conclusions: Full VSMC differentiation induced by TGF-b may not be achieved when extracellular phosphate levels are high. Moreover, TGF-b prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/b-catenin pathway.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/es_ES
dc.sourcePLoS ONE 9(6): e101910 (2014)es_ES
dc.subjectVascular calcificationes_ES
dc.subjectOsteogenesises_ES
dc.subjectGrowth factor-βes_ES
dc.subjectPhosphateses_ES
dc.subjectMesenchymal stem cellses_ES
dc.subjectCell differentiationes_ES
dc.subjectPhosphataseses_ES
dc.subjectDAPI staininges_ES
dc.titleTGF-β Prevents Phosphate-Induced Osteogenesis through Inhibition of BMP and Wnt/β-Catenin Pathwayses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0089179es_ES
dc.relation.projectIDJunta de Andalucía. P09-CTS-5205es_ES
dc.relation.projectIDJunta de Andalucía. PI-0127es_ES
dc.relation.projectIDInstituto de Salud Carlos III. FIS PI11/02055es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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