The Bone Morphogenetic Protein 2 Signaling Mediator Smad1 Participates Predominantly in Osteogenic and not in Chondrogenic Differentiation in Mesenchymal Progenitors C3H10T½

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  • Wenjun Ju
    Project-Group “Growth Factors and Receptors,” Gesellschaft für Biotechnologische Forschung (GBF), Braunschweig, Germany
  • Andrea Hoffmann
    Project-Group “Growth Factors and Receptors,” Gesellschaft für Biotechnologische Forschung (GBF), Braunschweig, Germany
  • Kristin Verschueren
    Department of Cell Growth, Differentiation and Development (VIB-07), Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Biology (Celgen), University of Leuven, Leuven, Belgium
  • Przemko Tylzanowski
    Laboratory for Skeletal Development and Joint Disorders, University of Leuven, Leuven, Belgium
  • Christian Kaps
    Project-Group “Growth Factors and Receptors,” Gesellschaft für Biotechnologische Forschung (GBF), Braunschweig, Germany
  • Gerhard Gross
    Project-Group “Growth Factors and Receptors,” Gesellschaft für Biotechnologische Forschung (GBF), Braunschweig, Germany
  • Danny Huylebroeck
    Department of Cell Growth, Differentiation and Development (VIB-07), Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Biology (Celgen), University of Leuven, Leuven, Belgium

Abstract

<jats:title>Abstract</jats:title> <jats:p>The role of the bone morphogenetic protein (BMP)-signaling mediator Smad1 in osteogenic or chondrogenic differentiation was investigated in murine parental mesenchymal progenitors C3H10T½ and its derivatives constitutively expressing BMP-2 (C3H10T½-BMP-2) and, therefore, undergo BMP-mediated osteogenic/chondrogenic development. The functions of the three Smad1 domains, that is, the N-terminal (MH1) domain, the C-terminal (MH2) domain, and the midregional proline-rich linker domain, were documented and compared with full-length Smad1. We showed that expression of the MH2 domain in parental C3H10T½ cells was sufficient to initiate osteogenic differentiation. Interestingly, MH1 was sufficient to initiate transcription of osteogenic marker genes like the osteocalcin or parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor. However, MH1 interfered with the histologically distinct formation of osteoblast-like cells. A dominant-negative effect on MH2-mediated osteogenic development in C3H10T½ cells was observed by the dose-dependent trans-expression of the midregional linker domain. Importantly, in contrast to osteogenic differentiation, Smad1 and its domains do not mimic or interfere with BMP-2-dependent chondrogenic development as monitored by the inability of MH2 to give rise to histologically distinct chondrocytes in parental C3H10T½ cells and by the inefficiency of the MH1 or linker domain to interfere with BMP-2-mediated chondrogenic differentiation.</jats:p>

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