title: Extracellular matrix deposition in cultured dermal fibroblasts from four probands affected by osteogenesis imperfecta.
abstract: Type I procollagen biosynthesis and matrix deposition were studied in cultured fibroblasts of four probands affected by Osteogenesis Imperfecta and in whom the mutations have been characterized. The mutations along the triple helix altered all biochemical parameters considered, i.e. thermal stability, kinetics of procollagen secretion and rate of maturation from procollagen to collagen. The biochemical findings were peculiar for each case considered, but there was no correlation between biochemical parameters and clinical phenotype. In all our probands, regardless of the clinical severity, mutant chains appeared in the insoluble matrix formed by fibroblasts cultured in the presence of dextran sulfate. The densitometric scanning revealed a relative increased amount of fibronectin, suggesting that the matrix contained a lower quantity of type I collagen. Furthermore, the amount of mutant chains found in the insoluble fraction was clearly less than expected, considering that 75% of new synthesized trimers are abnormal. Therefore, in the presence of a mutation, the protein available for extracellular matrix formation is reduced and the mutant trimers incorporated in the matrix probably interfere with normal fibril performance. The abnormal fibril morphology has a dramatic effect in bone, interfering presumably with a correct mineral deposition and interactions with non/collagenous bone proteins.
authors.affiliation: Dipartimento di Biochimica, University of Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Valli
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: Forlino
authors.forename: R
authors.initials: R
authors.lastname: Tenni
authors.forename: G
authors.initials: G
authors.lastname: Cetta
mesh_terms: D002478:Cells, Cultured; D002648:Child; D003094:Collagen / Q000096:biosynthesis* / Q000302:isolation & purification; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D010013:Osteogenesis Imperfecta / Q000378:metabolism / Q000473:pathology*; D011347:Procollagen / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012867:Skin / Q000378:metabolism / Q000473:pathology*
chemical_list: D011347:Procollagen; D003094:Collagen