Deposition of mutant type I collagen in the extracellular matrix of cultured dermal fibroblasts in osteogenesis imperfecta.
To study how mutant type I collagen interferes with matrix deposition we investigated the extracellular matrix produced by cultured skin fibroblasts in thirteen patients affected by different forms of Osteogenesis Imperfecta. Two different approaches were used: a) the pericellular matrix produced during 24 h label was analyzed by SDS-PAGE; b) type I collagen present in the insoluble cell-layer fraction in long-term cultures was studied. Results showed that a very small amount of abnormal type I trimers were present regardless of the clinical phenotype. In only two cases mutant chains were clearly incorporated. These data indicate a selective deposition of normal collagen trimers over abnormal ones. Moreover, in long-term cultures a decreased amount of type I collagen was deposited as indicated by the relative increase in type V collagen. These data are discussed in light of results found in bone by other authors and suggest that decreased deposition of type I collagen could be a general feature in OI and not limited to null-allele OI probands.
Cetta
G
G
Dipartimento di Biochimica, Università di Pavia, Italy.
Rossi
A
A
Tenni
R
R
Valli
M
M
Forlino
A
A
Zanaboni
G
G
Dyne
K
K
Burgio
G R
GR
D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000378:metabolism* / Q000473:pathology*; D010449:Peptide Mapping; D010641:Phenotype; D012867:Skin / Q000473:pathology*
D003094:Collagen