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Stromal cells of fibrodysplasia ossificans progressiva lesions express smooth muscle lineage markers and the osteogenic transcription factor Runx2/Cbfa-1: clues to a vascular origin of heterotopic ossification?

Authors

  • Laszlo Hegyi,

    1. Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK
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  • Francis H Gannon,

    1. Department of Orthopaedic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA
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  • David L Glaser,

    1. Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
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  • Eileen M Shore,

    1. Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    2. Department of Genetics, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
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  • Frederick S Kaplan,

    1. Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    2. Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
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  • Catherine M Shanahan

    Corresponding author
    1. Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK
    • Department of Medicine, Addenbrooke's Centre for Clinical Investigation, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
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Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare heritable genetic disorder, which is characterized pathologically by sporadic episodes of explosive growth of mesenchymal cells in skeletal muscle followed by cellular differentiation to heterotopic bone through an endochondral process. This study examined the histological origin and differentiation state of stromal cells in early FOP lesions and investigated the association between the phenotype of these FOP cells and bone formation. Interestingly, FOP lesional stromal cells were found to display characteristics of the smooth muscle (SM) cell lineage and are therefore potentially of vascular origin. These cells co-express multiple SM lineage markers along with multiple proteins associated with bone formation including the obligate osteogenic transcription factor Runx2/Cbfa-1. It is hypothesized that the stromal cells of early FOP lesions may be locally recruited vascular cells or cells of the bone marrow stroma and that these cells maintain the potential (given the correct environmental stimuli) to differentiate along an endochondral ossification pathway. Copyright © 2003 John Wiley & Sons, Ltd.

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