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

Biochem Biophys Res Commun. 2008 Feb 22;366(4):1074-80. doi: 10.1016/j.bbrc.2007.12.095. Epub 2007 Dec 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects*
  • Calcium / metabolism
  • Cell Differentiation / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development / drug effects
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Proto-Oncogene Proteins c-kit / metabolism
  • Signal Transduction / drug effects
  • Stem Cells / cytology*
  • Stem Cells / drug effects*
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-kit
  • Calcium