NOV/CCN3 impairs muscle cell commitment and differentiation |
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Authors: | Calhabeu Frederico Lafont Jérome Le Dreau Gwenvael Laurent Maryvonne Kazazian Chantal Schaeffer Laurent Martinerie Cécile Dubois Catherine |
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Affiliation: | Unité INSERM 515, H?pital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75371 Paris, France; Pierre and Marie Curie University, Paris. |
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Abstract: | NOV (nephroblastoma overexpressed) is a member of a family of proteins which encodes secreted matrix-associated proteins. NOV is expressed during development in dermomyotome and limb buds, but its functions are still poorly defined. In order to understand the role of NOV in myogenic differentiation, C2C12 cells overexpressing NOV (C2-NOV) were generated. These cells failed to engage into myogenic differentiation, whereas they retained the ability to differentiate into osteoblasts. In differentiating conditions, C2-NOV cells remained proliferative, failed to express differentiation markers and lost their ability to form myotubes. Inhibition of differentiation by NOV was also observed with human primary muscle cells. Further examination of C2-NOV cells revealed a strong downregulation of the myogenic determination genes MyoD and Myf5 and of IGF-II expression. MyoD forced expression in C2-NOV was sufficient to restore differentiation and IGF-II induction whereas 10(-6) M insulin treatment had no effects. NOV therefore acts upstream of MyoD and does not affect IGF-II induction and signaling. HES1, a target of Notch, previously proposed to mediate NOV action, was not implicated in the inhibition of differentiation. We propose that NOV is a specific cell fate regulator in the myogenic lineage, acting negatively on key myogenic genes thus controlling the transition from progenitor cells to myoblasts. |
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Keywords: | CCN family HES1 IGF-II IGFBP Myf5 MyoD Myogenin Myogenic differentiation NOV p21CIP1/WAF1 Skeletal muscle cells |
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