Deposition and selective degradation of structually-abnormal type I collagen in a collagen matrix produced by osteogenesis imperfecta fibroblasts in vitro

Abstract

Collagen matrix deposition and turnover were studied in skin fibroblasts from a control and from a patient with lethal perinatal osteogenesis imperfecta (OI) identified as a Gly667 to Arg substitution in the α1(I) chain. A culture system where ascorbic acid was included to stimulate collagen matrix formaton over extended culture periods was used. Serial extraction of the control cell collagen matrix confirmed that a substantial mature crosslinked collagen matrix was formed in the control fibroblast cell layer. In contrast, total collagen deposition by the OI fibroblasts was poor, with the quantity of collagen deposited only about a quarter of that of the control cells. Detailed analysis of t..