Bone Morphogenetic Protein-4 Influences NeuralDifferentiation of Induced Mouse Mesenchymal Stem Cells

Objective: Members of the transforming growth factor-B superfamily, including bone mor- phogenetic protein 4 (BMP4), have been implicated as regulators of neural differentiation. The aim of this study was to establish whether BMP4 could influence neuronal differentia- tion of mesenchymal stem cells (MSCs). Materials and Methods: Therefore, neuronal differentiation of MSCs was induced by ba- sic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) and treatment. The expression of neuronal specific markers such as Nestin, MAP2, B-Tubulin III and NKX6.1 were detected by RT-PCR, flow cytometery and/or immunostaining. Results: While the percentage of Nestin positive cells was increased significantly during treatment, the addition of BMP4 during the first 4 days of treatment with bFGF and EGF reduced Nestin expression as showed by flow cytometry. This observation was further confirmed by relative gene expression which showed the reduction in expression of neural markers such as Nestin, MAP2 and NKX6.1 following treatment with BMP4. Conclusion: The results of this study suggest that BMP4 downregulates the neural fate of induced mouse MSCs.