Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.
AUTOR(ES)
Barsh, G S
RESUMO
Osteogenesis imperfecta is a clinically and genetically heterogeneous group of inherited connective tissue disorders in which bone fragility is the predominant feature. Cultured dermal fibroblasts from one patient with the lethal perinatal form of osteogenesis imperfecta secrete type I procollagen at a rate half that of normal cells. Short-term labeling experiments and treatment with alpha,alpha'-dipyridyl (which prevents posttranslational prolyl and lysyl hydroxylation) demonstrated that these cells produce two distinct pro alpha 1(I) chains, which are synthesized at the same rate. Analysis of cyanogen bromide peptides indicated that the two chains differ in their primary structures. Thus, structural abnormalities in type I procollagen prevent this molecule from being secreted normally, resulting in an anomalously low ratio of type I procollagen to other extracellular matrix molecules. While the lethal perinatal form of osteogenesis imperfecta may be heterogeneous, we propose that the underlying pathogenesis of at least one form is decreased secretion of type I procollagen.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=320349Documentos Relacionados
- Abnormal alpha 2-chain in type I collagen from a patient with a form of osteogenesis imperfecta.
- A new type of osteogenesis imperfecta.
- Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta.
- Restriction fragment length polymorphism associated with the pro alpha 2(I) gene of human type I procollagen. Application to a family with an autosomal dominant form of osteogenesis imperfecta.
- Lethal osteogenesis imperfecta.