Mechanical signals and IGF-I gene splicing in vitro in relation to development of skeletal muscle

Authors

  • Umber Cheema,

    1. Institute of Orthopaedics and Musculo-skeletal Science, University College London, Middlesex, United Kingdom
    2. Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom
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  • Robert Brown,

    1. Institute of Orthopaedics and Musculo-skeletal Science, University College London, Middlesex, United Kingdom
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  • Vivek Mudera,

    1. Institute of Orthopaedics and Musculo-skeletal Science, University College London, Middlesex, United Kingdom
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  • Shi Yu Yang,

    1. Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom
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  • Gus McGrouther,

    1. Plastic and Reconstructive Surgery Research, The University of Manchester, Manchester, United Kingdom
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  • Geoffrey Goldspink

    Corresponding author
    1. Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom
    • Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
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Abstract

It has been shown that the insulin-like growth factor (IGF-I) gene is spliced in response to mechanical signals producing forms of IGF-I which have different actions. In order to study how mechanical signals influence this gene splicing in developing muscle, C2C12 cells were grown in three-dimensional (3D) culture and subjected to different regimens of mechanical strain. IGF-IEa which initiates the fusion of myoblasts to form myotubes was found to be constitutively expressed in myoblasts and myotubes (held under endogenous tension) and its expression upregulated by a single ramp stretch of 1-h duration but reduced by repeated cyclical stretch. In contrast, mechano growth factor (MGF), which is involved in the proliferation of mononucleated myoblasts that are required for secondary myotube formation and to establish the muscle satellite (stem) cell pool, showed no significant constitutive expression in static cultures, but was upregulated by a single ramp stretch and by cycling loading. The latter types of force simulate those generated in myoblasts by the first contractions of myotubes. These data indicate the importance of seeking to understand the physiological signals that determine the ratios of splice variants of some growth factor/tissue factor genes in the early stages of development of skeletal muscle. © 2005 Wiley-Liss, Inc.

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