Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP).
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.
Kaplan
Frederick S
FS
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.kaplan@uphs.upenn.edu
Shen
Qi
Q
Lounev
Vitali
V
Seemann
Petra
P
Groppe
Jay
J
Katagiri
Takenobu
T
Pignolo
Robert J
RJ
Shore
Eileen M
EM
D030201:Activin Receptors, Type I / Q000235:genetics; D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000502:physiology; D009139:Musculoskeletal Abnormalities / Q000473:pathology; D020125:Mutation, Missense; D009221:Myositis Ossificans / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D012863:Skeleton; D013234:Stem Cells / Q000502:physiology; D023822:Tissue Engineering
D019485:Bone Morphogenetic Proteins; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; D052004:Bone Morphogenetic Protein Receptors