MMP-9 overexpression improves myogenic cell migration and engraftment

Authors

  • Jennifer Morgan PhD,

    1. UCL Institute of Child Health, 30 Guilford Street, London WC1N1EH, UK
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  • Andrée Rouche MS,

    1. INSERM U582 (now UMRS 974), Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
    2. Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 582, Institut Fédératif de Recherche, Paris, France
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  • Pedro Bausero PhD,

    1. INSERM U582 (now UMRS 974), Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
    2. Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 582, Institut Fédératif de Recherche, Paris, France
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  • Amal Houssaïni MS,

    1. INSERM U582 (now UMRS 974), Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
    2. Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 582, Institut Fédératif de Recherche, Paris, France
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  • Jacqueline Gross MS,

    1. UCL Institute of Child Health, 30 Guilford Street, London WC1N1EH, UK
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  • Marc Y. Fiszman PhD,

    1. INSERM U582 (now UMRS 974), Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
    2. Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 582, Institut Fédératif de Recherche, Paris, France
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  • Hala S. Alameddine PhD

    Corresponding author
    1. INSERM U582 (now UMRS 974), Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
    2. Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 582, Institut Fédératif de Recherche, Paris, France
    • INSERM UMRS 974, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France
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Abstract

Myoblast migration requires matrix metalloproteinase (MMP) activity but the contribution of individual MMPs or tissue inhibitors of matrix metalloproteinase (TIMPs), particularly MMP-9 and TIMP-1, is lacking. Using two clones derived for differential regulation of MMP-2, MMP-9, and TIMP-1, we correlated protein expression with cell migration. MMP/TIMP regulation was determined by zymography, western blots, and quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR). Cell migration was compared in vitro and after grafting into nudemdx mouse muscles. C2M9 clones produced high MMP-9 and low MMP-2, and migrated better than C2F clones, which secreted low MMP-9, but overexpressed MMP-2 and TIMP-1. Improvement of C2F invasion by MMP-9 and inhibition of C2M9 migration by MMP-9 inhibitor I confirmed the role of MMP-9 and pointed to potential inhibition by TIMP-1. Higher complementation achieved by C2M9 grafts corroborated the beneficial effect of MMP-9 overexpression. Modulation of MMP-9 expression opens perspectives for improved efficacy of cell therapy for muscular dystrophies. Muscle Nerve, 2010

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