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Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP)

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Abstract

Metamorphosis, the transformation of one normal tissue or organ system into another, is a biological process rarely studied in higher vertebrates or mammals, but exemplified pathologically by the extremely disabling autosomal dominant disorder fibrodysplasia ossificans progressiva (FOP). The recurrent single nucleotide missense mutation in the gene encoding activin receptor IA/activin-like kinase-2 (ACVR1/ALK2), a bone morphogenetic protein type I receptor that causes skeletal metamorphosis in all classically affected individuals worldwide, is the first identified human metamorphogene. Physiological studies of this metamorphogene are beginning to provide deep insight into a highly conserved signaling pathway that regulates tissue stability following morphogenesis, and that when damaged at a highly specific locus (c.617G > A; R206H), and triggered by an inflammatory stimulus permits the renegade metamorphosis of normal functioning connective tissue into a highly ramified skeleton of heterotopic bone. A comprehensive understanding of the process of skeletal metamorphosis, as revealed by the rare condition FOP, will lead to the development of more effective treatments for FOP and, possibly, for more common disorders of skeletal metamorphosis.

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Authors and Affiliations

  1. Departments of Orthopaedic Surgery and Medicine, c/o Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Silverstein 2, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Frederick S. Kaplan

  2. Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Qi Shen & Vitali Lounev

  3. Max Planck Institute for Molecular Genetics, Development and Disease, Berlin, Germany

    Petra Seemann

  4. Department of Biomedical Sciences, Baylor College of Dentistry, Texas A & M University Health Science Center, Dallas, TX, USA

    Jay Groppe

  5. Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan

    Takenobu Katagiri

  6. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Robert J. Pignolo

  7. Departments of Orthopaedic Surgery & Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Eileen M. Shore

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  1. Frederick S. Kaplan
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Correspondence to Frederick S. Kaplan.

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Kaplan, F.S., Shen, Q., Lounev, V. et al. Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP). J Bone Miner Metab 26, 521–530 (2008). https://doi.org/10.1007/s00774-008-0879-8

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