Dysregulation of the BMP-4 signaling pathway in fibrodysplasia ossificans progressiva.

Identification of gene mutations in Mendelian disorders is often determined by linkage analysis and positional cloning, an approach that is difficult for fibrodysplasia ossificans progressiva (FOP) due to a low reproductive fitness that results in a small number of multigenerational families showing inheritance of the disease. Altered signaling pathways can be investigated as a complementary method to identify the consequences of the mutated gene responsible for FOP and to identify potential therapeutic targets. Candidate signaling pathways for FOP are those that malfunctioning could account for the malformation of the great toes during embryonic development and could explain the postnatal progressive heterotopic endochondral ossification.

Dysregulation of the BMP-p38 MAPK signaling pathway in cells from patients with fibrodysplasia ossificans progressiva (FOP).

Unlabelled: FOP is a disabling disorder in which skeletal muscle is progressively replaced with bone. Lymphocytes, our model system for examining BMP signaling, cannot signal through the canonical Smad pathway unless exogenous Smad1 is supplied, providing a unique cell type in which the BMP-p38 MAPK pathway can be examined. FOP lymphocytes exhibit defects in the BMP-p38 MAPK pathway, suggesting that altered BMP signaling underlies ectopic bone formation in this disease.

Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA.

Unlabelled: FOP is a disorder in which skeletal muscle is progressively replaced with bone. FOP lymphocytes, a model system for exploring the BMP pathway in these patients, exhibit a defect in BMPRIA internalization and increased activation of downstream signaling, suggesting that altered BMP receptor trafficking underlies ectopic bone formation in this disease.

Introduction: Fibrodysplasia ossificans progressiva (FOP) is a severely disabling disorder characterized by progressive heterotopic ossification of connective tissues.

Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis.

Background: Fibrodysplasia ossificans progressiva is a rare genetic disorder characterized by congenital malformations of the great toes and by progressive heterotopic bone formation. Bone morphogenetic protein-4 (BMP-4) messenger ribonucleic acid (mRNA) and protein are uniquely overexpressed in lymphocytes and lesional cells from patients who have fibrodysplasia ossificans progressiva. However, the BMP-4 gene is not mutated in fibrodysplasia ossificans progressiva.