BMP signaling and skeletal development in fibrodysplasia ossificans progressiva (FOP). Issue 1 (26th June 2021)

• Record Type: Journal Article
• Authors: Towler, Oscar Will; Shore, Eileen M.
• Other Names: Christian Jan L. guestEditor.; Hill Caroline S. guestEditor.
• Is Part Of: Developmental dynamics. Volume 251:Issue 1(2022)
• Page Start: 144
• Page End: 157
• Publication Date: 2021-06-26
• Subjects: ACVR1 -- bone morphogenetic protein -- fibrodysplasia ossificans progressiva -- FOP -- heterotopic ossification -- joint development -- toe/digit malformation; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.387
• Languages: English
• ISSNs: 1058-8388

Abstract

Abstract: Fibrodysplasia ossificans progressiva (FOP) is an ultra‐rare genetic disease caused by increased BMP pathway signaling due to mutation of ACVR1, a bone morphogenetic protein (BMP) type 1 receptor. The primary clinical manifestation of FOP is extra‐skeletal bone formation (heterotopic ossification) within soft connective tissues. However, the underlying ACVR1 mutation additionally alters skeletal bone development and nearly all people born with FOP have bilateral malformation of the great toes as well as other skeletal malformations at diverse anatomic sites. The specific mechanisms through which ACVR1 mutations and altered BMP pathway signaling in FOP influence skeletal bone formation during development remain to be elucidated; however, recent investigations are providing a clearer understanding of the molecular and developmental processes associated with ACVR1‐regulated skeletal formation. Key Findings: FOP is caused by dysregulated BMP pathway activity that alters bone formation, both through induction of extra‐skeletal (heterotopic) ossification and through skeletal developmental defects. The endogenous skeleton of individuals with FOP is affected, particularly at the joints, at multiple sites throughout the body. The developmental skeletal phenotype of FOP shows similarities to other models of altered BMP pathway signaling, providing insight into the causative molecular mechanisms.