RESUMO
Bone morphogenetic protein 4, a potent osteogenic morphogen, has been implicated in fibrodysplasia ossificans progressiva because it is uniquely overexpressed in lymphoblastoid cells and preosseous fibroproliferative lesional cells of patients with fibrodysplasia ossificans progressiva. Bone morphogenetic protein 4 signals through a heteromeric complex of serine/ threonine kinase receptors (type I and type II) on the surface of responding cells. Semi-quantitative competitive reverse transcription polymerase chain reaction was used to quantitate steady state levels of messenger ribonucleic acid expression for bone morphogenetic 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 autosomal dominant inheritance of fibrodysplasia ossificans progressiva. There were no differences in the steady state levels of messenger ribonucleic acid for either the Type I or Type II bone morphogenetic protein 4 receptors between affected and unaffected individuals in that same family. The presence of bone morphogenetic protein 4 receptor messenger ribonucleic acid in fibrodysplasia ossificans progressiva lesional tissue and unaffected muscle tissue and demonstrates the deregulation of bone morphogenetic protein 4 messenger ribonucleic acid in fibrodysplasia ossificans progressiva. These data support the hypothesis that the molecular basis of bone morphogenetic protein 4 signaling is abnormal in fibrodysplasia ossificans progressiva.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Miosite Ossificante/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Fatores de Crescimento , Proteína Morfogenética Óssea 4 , Receptores de Proteínas Morfogenéticas Ósseas , Células Cultivadas , Criança , Feminino , Humanos , Miosite Ossificante/genética , Linhagem , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Transcrição Gênica , Células Tumorais CultivadasRESUMO
In patients who have fibrodysplasia ossificans progressiva, routine childhood diphtheria-tetanus-pertussis immunizations administered by intramuscular injection caused a significant risk of permanent heterotopic ossification at the site of injection (p < 10(-8)), whereas measles-mumps-rubella immunizations administered by subcutaneous injection posed no significant risk. Intramuscular injections should be avoided, if possible, once a diagnosis of fibrodysplasia ossificans progressiva has been established.