Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis

Frederick S Kaplan; Mona Al Mukaddam; Alexandra Stanley; O Will Towler; Eileen M Shore

doi:10.1016/j.bone.2020.115539

Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis

Bone. 2020 Nov:140:115539. doi: 10.1016/j.bone.2020.115539. Epub 2020 Jul 27.

Authors

Frederick S Kaplan¹, Mona Al Mukaddam², Alexandra Stanley³, O Will Towler⁴, Eileen M Shore⁵

Affiliations

¹ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Frederick.Kaplan@pennmedicine.upenn.edu.
² Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Mona.AlMukaddam@pennmedicine.upenn.edu.
³ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: astanley@health.ucsd.edu.
⁴ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: otowler@pennmedicine.upenn.edu.
⁵ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shore@pennmedicine.upenn.edu.

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder of extraskeletal bone formation, but could appropriately be viewed as a seminal disorder of osteochondrogenesis. Many, if not most, of the musculoskeletal features of FOP are related to dysregulated chondrogenesis including abnormal articular cartilage formation, abnormal diarthrodial joint specification, growth plate dysplasia, osteochondroma formation, heterotopic endochondral ossification (HEO), and precocious arthropathy. In FOP, causative activating mutations of Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor, are responsible for the osteochondrodysplasia that impacts developmental phenotypes as well as postnatal features of this illustrative disorder. Here, we highlight the myriad developmental and postnatal effects on osteochondrogenesis that emanate directly from mutant ACVR1 and dysregulated bone morphogenetic protein (BMP) signaling in FOP.

Keywords: ACVR1; Arthropathy; Bone morphogenetic protein signaling pathway; Degenerative joint disease; Fibrodysplasia ossificans progressiva; Growth plate; Heterotopic ossification; Osteochondrodysplasia; Osteochondrogenesis; Osteochondroma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Activin Receptors, Type I / genetics
Bone Morphogenetic Proteins
Chondrogenesis
Humans
Myositis Ossificans* / genetics
Ossification, Heterotopic* / genetics

Substances

Bone Morphogenetic Proteins
Activin Receptors, Type I

Abstract

Publication types

MeSH terms

Substances

Grants and funding