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 fib roblasts in thirteen patients affected by different forms of Osteogene sis Imperfecta. Two different approaches were used: a) the pericellula r 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 c ultures was studied. Results showed that a very small amount of abnorm al type I trimers were present regardless of the clinical phenotype. I n only two cases mutant chains were clearly incorporated. These data i ndicate a selective deposition of normal collagen trimers over abnorma l ones. Moreover, in long-term cultures a decreased amount of type I c ollagen was deposited as indicated by the relative increase in type V collagen. These data are discussed in light of results found in bone b y other authors and suggest that decreased deposition of type I collag en could be a general feature in OI and not limited to null-allele OI probands.