CHARACTERIZATION OF BONE MORPHOGENETIC PROTEIN-4 RECEPTOR IN FIBRODYSPLASIA OSSIFICANS PROGRESSIVA

Bone morphogenetic protein 4, a potent osteogenic morphogen, has been implicated in fibrodysplasia ossificans progressiva because it is uniq uely overexpressed in lymphoblastoid cells and preosseous fibroprolife rative lesional cells of patients with fibrodysplasia ossificans progr essiva. Bone morphogenetic protein 4 signals through a heteromeric com plex of serine/threonine kinase receptors (type I and type II) on the surface of responding cells. Semiquantitative competitive reverse tran scription polymerase chain reaction was used to quantitate steady stat e levels of messenger ribonucleic acid expression for bone morphogenet ic protein 4 and the bone morphogenetic protein receptors. These data confirmed the previous finding of elevated steady state levels of bone morphogenetic protein 4 messenger ribonucleic acid in lymphoblastoid cell lines of affected individuals in a family that exhibited autosoma l dominant inheritance of fibrodysplasia ossificans progressiva. There were no differences in the steady state levels of messenger ribonucle ic acid for either the Type I or Type II bone morphogenetic protein 4 receptors between affected and unaffected individuals in that same fam ily. The presence of bone morphogenetic protein 4 receptor messenger r ibonucleic acid in fibrodysplasia ossificans progressiva lesional tiss ue and unaffected muscle tissue and demonstrates the deregulation of b one morphogenetic protein 4 messenger ribonucleic acid in fibrodysplas ia ossificans progressiva. These data support the hypothesis that the molecular basis of bone morphogenetic protein 4 signaling is abnormal in fibrodysplasia ossificans progressiva.