Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta

Abstract

Cultured skin fibroblasts from seven consecutive cases of lethal perinatal osteogenesis imperfecta (OI) expressed defects of type I collagen metabolism. The secretion of [14C]proline-labelled collagen by the OI cells was specifically reduced (51-79% of control), and collagen degradation was increased to twice that of control cells in five cases and increased by approx. 30% in the other two cases. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that four of the OI cell lines produced two forms of type I collagen consisting of both normally and slowly migrating forms of the α1(I)- and α2(I)-chains. In the other three OI cell lines only the 'slow' α(I)'- and α2(I)'-chains we..