Guerrero, FátimaHerencia, CarmenAlmadén, YolandaCanalejo Raya, Antonio2020-07-202020-07-202014-02Guerrero, 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.00891791932-6203http://hdl.handle.net/10272/18561Background: 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.engAtribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/TGF-bPhosphate-InducedOsteogenesisInhibition of BMPWnt/b-Cateninjournal article10.1371/journal.pone.0089179open access