TGF-beta induces the differentiation of bone marrow stem cells into immature cardiomyocytes.

Transforming growth factor-beta(1) (TGF-beta(1)) was found to induce the myogenic differentiation of bone marrow stem cells (BMSC). We investigated the morphological and electrophysiological properties of differentiated cells, and the mechanisms related to TGF-beta(1)-induced myogenic differentiation. We found that TGF-beta increased the expression of the cardiac transcription factors, GATA-4 and NKx-2.5, in BMSC after 1-3 days of cultivation. TGF-beta also induced the expressions of cardiac myosin, troponins, and ANP after 3-14 days of cultivation. However, the Ca(2+) transient was relatively weak, the connexin-43 expression was irregular, and spontaneous beating was not detected within 28 days observation. TGF-beta stimulation up-regulated most of the TGF-beta BMP signaling pathway genes, including TGFBI, ACVR2B, and phosphorylated Smad-2 and Smad-3, within 24h. TGF-beta induced the differentiation of BMSC into immature cardiomyocytes by activating the TGF-beta BMP signaling pathway.