@article{10272/18561,
year = {2014},
month = {2},
url = {http://hdl.handle.net/10272/18561},
abstract = {Background: 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.},
organization = {Sources of Funding: This study has been carried out with the funding of ‘‘Proyecto de Excelencia P09-CTS-5205’’ from Consejerı ́a de Economı ́a, Cienciay Empresa from Junta de Andalucı ́a, FIS PI11/02055 from Instituto de Salud Carlos III and PI-0127 from Consejerı ́a de Salud, Junta de Andalucia. The funders hadno role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.},
publisher = {Public Library of Science},
title = {TGF-b Prevents Phosphate-Induced Osteogenesis through Inhibition of BMP and Wnt/b-Catenin Pathways},
doi = {10.1371/journal.pone.0089179},
author = {Guerrero, Fátima and Herencia, Carmen and Almadén, Yolanda and Canalejo Raya, Antonio},
}