Signal transducer and activator of transcription 3—A key molecular switch for human mesenchymal stem cell proliferation

Abstract

Human bone marrow mesenchymal stem cells are multipotent cells with enormous potential for cellular therapies. Identifying those mediators that induce human bone marrow mesenchymal stem cell proliferation and elucidating the signaling networks involved will encourage clinical efforts exploiting such cells. Here, we demonstrate that platelet-derived growth factor-BB and basic fibroblast growth factor induce human bone marrow mesenchymal stem cell proliferation. Platelet-derived growth factor-BB induced human bone marrow mesenchymal stem cell proliferation via complete activation of the Janus-activated kinase-signal transducers and activators of transcription cascade, inducing signal transducer and activator of transcription 3 tyrosine and serine phosphorylation as well as Janus-activated kinase 2 tyrosine phosphorylation. Janus-activated kinase 2 was required for signal transducer and activator of transcription 3 tyrosine phosphorylation, whereas the extracellular signal-regulated kinase 1/2 mediated signal transducer and activator of transcription 3 serine phosphorylation in response to platelet-derived growth factor-BB. Furthermore, platelet-derived growth factor-BB was shown to promote nuclear translocation of signal transducer and activator of transcription 3. By contrast, basic fibroblast growth factor-stimulated human bone marrow mesenchymal stem cell proliferation was mediated via the extracellular signal-regulated kinase 1/2 pathway without involvement of the Janus-activated kinase-signal transducers and activators of transcription cascade. Importantly, platelet-derived growth factor-BB and basic fibroblast growth factor induced human bone marrow mesenchymal stem cell proliferation without affecting their osteogenic differentiation potential. Together, our study highlights the role of several growth factors in human bone marrow mesenchymal stem cell proliferation and the signaling pathways involved in the process. This information is crucial for achieving a better control over the human bone marrow mesenchymal stem cell expansion process.