Small concentrations of TGF-β1 promote proliferation of bone marrow-derived mesenchymal stem cells via activation of Wnt/β-catenin pathway.
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, Aktl, 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, Aktl, 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.
Fenxi
F
Zhang
Tongming
T
Ren
Junfang
J
Wu
Jie
J
Niu
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
D053773:Transforming Growth Factor beta1; D051176:beta Catenin