Secreted Collagen Ratios in Normal Human and Osteogenesis Imperfecta Skin Fibroblasts

Publisher Website
Google Scholar
Abstract
The effects of several variables on the ratio of type I:type III collagen secreted by human caucasian skin fibroblasts in normal and osteogenesis imperfecta (OI) phenotypes were examined. Isotopically labeled collagen extracted from fibroblast medium was analyzed by DEAE-cellulose chromatography and identified by appropriate methods. Type I procollagen was the major form of collagen secreted into the medium by normal cells cultured from mid-term fetus (1), infants (3), children (3), adolescents (2) and adults (3). Interstrain differences in collagen production under standardized conditions were significantly greater than intrastrain variation (anova, P = 0.0051). There was no significant alteration in the type I:type III collagen ratio due to variation in phase of cell growth, doublings (between 13th and 22nd), rate of isotope incorporation, labeling time (24-72 h) in the presence of ascorbic acid (50 .mu.g/ml), age of donor (with the possible exception of adolescence) and site of biopsy (genital and non-genital sites). Variable conversion of type I procollagen to collagen did not perturb the type I:type III collagen ratio. Cell strains from OI patients (Sillence classification): type I (1 strain); type II, III and IV (3 strains each) had greater interstrain than intrastrain variation in the collagen ratio (P = 0.0149). Interstrain differences were greater in OI cell strains relative to normal cell strains (P < 0.01) In the aggregate, OI cells had significantly lower type I collagen production relative to type III (I/III ratio = 1.18) when compared with normal cells (I/III ratio = 2.90; t test, P < 0.0001). These findings imply abnormal synthesis, secretion or stability of type I procollagen and greater phenotypic heterogeneity in OI skin fibroblasts relative to normal cells.