Journal of Bone and Mineral Metabolism

, Volume 26, Issue 6, pp 521–530

Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP)

  • Frederick S. Kaplan
  • Qi Shen
  • Vitali Lounev
  • Petra Seemann
  • Jay Groppe
  • Takenobu Katagiri
  • Robert J. Pignolo
  • Eileen M. Shore
Open Access
Review Article

DOI: 10.1007/s00774-008-0879-8

Cite this article as:
Kaplan, F.S., Shen, Q., Lounev, V. et al. J Bone Miner Metab (2008) 26: 521. doi:10.1007/s00774-008-0879-8

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.

Key words

morphogen metamorphogene ACVR1 fibrodysplasia ossificans progressiva (FOP) bone morphogenetic protein (BMP) BMP receptor heterotopic ossification 
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Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Frederick S. Kaplan
    • 1
  • Qi Shen
    • 2
  • Vitali Lounev
    • 2
  • Petra Seemann
    • 3
  • Jay Groppe
    • 4
  • Takenobu Katagiri
    • 5
  • Robert J. Pignolo
    • 6
  • Eileen M. Shore
    • 7
  1. 1.Departments of Orthopaedic Surgery and Medicine, c/o Department of Orthopaedic SurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Orthopaedic SurgeryUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Max Planck Institute for Molecular Genetics, Development and DiseaseBerlinGermany
  4. 4.Department of Biomedical Sciences, Baylor College of DentistryTexas A & M University Health Science CenterDallasUSA
  5. 5.Division of Pathophysiology, Research Center for Genomic MedicineSaitama Medical UniversitySaitamaJapan
  6. 6.Department of MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  7. 7.Departments of Orthopaedic Surgery & GeneticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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