Small concentrations of TGF-β1 promote proliferation of bone marrow-derived mesenchymal stem cells via activation of Wnt/β-catenin pathway.

ABSTRACT

Bone marrow-derived mesenchymal stem cells (BMSCs) are the most promising seed cells for cell transplant. The proliferation of BMSCs is one of the most important determinants of the efficiency of MSC-based transplant therapy. It has been reported that transforming growth factor-β1 (TGF-β1) activates Wnt/β-catenin signaling and regulates cell proliferation. In this study, we investigated the effect of low concentrations of TGF-β1 on proliferation of BMSCs and the related mechanisms. BMSCs were treated with 0, 1, 5 and 10 ng/L recombinant mouse TGF-β1 for 12 h. Cell proliferation was measured by cell counting and MTT assay, and the proliferation-related signals p53, Mdm2, Akt1, Wnt3, phospho-Akt and β-catenin were measured by quantitative polymerase chain reaction (qPCR) and/or Western blot. Our results showed that TGF-β1 at low concentrations induced BMSC proliferation and expression of Mdm2, Akt1, phospho-Akt, Wnt3 and β-catenin, and inhibited p53 expression in dose dependent manner. Importantly, β-catenin siRNA significantly inhibited TGF-β1-induced BMSC proliferation. These findings suggest that low concentrations of TGF-β1 can stimulate proliferation of BMSCs, which is at least partially dependent on the activation of Wnt/β-catenin pathway.