Abstract:

BACKGROUND: It remains unclear whether bone morphogenetic protein (BMP), Wnt, Notch, FGF and Hedgehog signaling pathways are involved in differentiation of cardiomyocytes from bone marrow-derived mesenchymal stem cells (BMSCs).
OBJECTIVE: To investigate the ability of BMSCs differentiating into cardiomyocytes-like cells and their differentiating mechanism of signal pathways in myocardial microenvironment.
METHODS: Myocardial microenvironment was established by the technology of Transwell, and Wnt11 and BMP2 were used to induce BMSCs differentiation into cardiomyocyte-like cells. RT-PCR and western blot were used to detect expression of key signaling molecules of BMP, Wnt, Notch, FGF and Hedgehog signaling pathways. In addition, expression of cardiac-specific transcription factors, Nkx2.5, GATA4, and Mef2c, and mature cardiac-specific genes, cTnI, ANP, α-MHC, and β-MHC, was detected.
RESULTS AND CONCLUSION: After co-culture with rat cardiomyocytes, in the BMSCs, the expression of key signaling molecules of Wnt, BMP, Notch, Hedgehog signal pathways was significantly higher than the non-induced negative control group (P < 0.01). After adding BMP signal pathway inhibitor, Noggin, cardiac-specific transcription factors or structural proteins Nkx-2.5, GATA4, α-MHC, β-MHC, cTnI expression was significantly reduced (P < 0.01). Results indicate that myocardial microenvironment can induce rat BMSCs to differentiate into cardiomyocyte-like cells. Wnt, BMP, Notch, FGF and Hedgehog signaling pathways were all involved in the process.