RT Journal Article
T1 TGF-b Prevents Phosphate-Induced Osteogenesis through Inhibition of BMP and Wnt/b-Catenin Pathways
A1 Guerrero, Fátima
A1 Herencia, Carmen
A1 Almadén, Yolanda
A1 Canalejo Raya, Antonio
AB 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 musclecells (VSMC) into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMCdifferentiation 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 smoothmuscle markers, such as smooth muscle alpha actin, SM22a, myocardin, and smooth muscle-myosin heavy chain. Theaddition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/bcateninin addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. Theadministration of TGF-b to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMPand TGF-b pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wntsignaling with Dkk-1. Conversely, addition of both Wnt/b-catenin activators CHIR98014 and lithium chloride enhanced theeffect 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 andavoiding the activation of Wnt/b-catenin pathway.
PB Public Library of Science
SN 1932-6203
YR 2014
FD 2014-02
LK http://hdl.handle.net/10272/18561
UL http://hdl.handle.net/10272/18561
LA eng
NO Guerrero, F., Herencia, C., Almadén, Y. ... Canalejo Raya, A. (2014). TGF-β Prevents Phosphate-Induced Osteogenesis through Inhibition of BMP and Wnt/β-Catenin Pathways. PLoS ONE, 9(2), e89179. DOI: https://doi.org/10.1371/journal.pone.0089179
NO 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.
DS Repositorio Institucional de la Universidad de Huelva
RD 13 jun 2026