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

Research output: Contribution to journalReview article

50 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)521-530
Number of pages10
JournalJournal of Bone and Mineral Metabolism
Volume26
Issue number6
DOIs
StatePublished - Nov 1 2008

Keywords

  • ACVR1
  • BMP receptor
  • Bone morphogenetic protein (BMP)
  • Fibrodysplasia ossificans progressiva (FOP)
  • Heterotopic ossification
  • Metamorphogene
  • Morphogen

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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    Kaplan, F. S., Shen, Q., Lounev, V., Seemann, P., Groppe, J., Katagiri, T., Pignolo, R. J., & Shore, E. M. (2008). Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP). Journal of Bone and Mineral Metabolism, 26(6), 521-530. https://doi.org/10.1007/s00774-008-0879-8