Dataset Information

TGF-? prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/?-catenin pathways.

ABSTRACT:

Background

Transforming growth factor-? (TGF-?) 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-? induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22?, 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/?-catenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-? to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-? 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/?-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-? may not be achieved when extracellular phosphate levels are high. Moreover, TGF-? prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/?-catenin pathway.

SUBMITTER: Guerrero F

PROVIDER: S-EPMC3937350 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways.

Guerrero Fátima F Herencia Carmen C Almadén Yolanda Y Martínez-Moreno Julio M JM Montes de Oca Addy A Rodriguez-Ortiz María Encarnación ME Diaz-Tocados Juan M JM Canalejo Antonio A Florio Mónica M López Ignacio I Richards William G WG Rodriguez Mariano M Aguilera-Tejero Escolástico E Muñoz-Castañeda Juan R JR

PloS one 20140227 2

<h4>Background</h4>Transforming growth factor-β (TGF-β) 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.<h4>Results</h4>Our results showed that TGF-β induced nuclear translocation of ...[more]

PMID: 24586576

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