title: Osteogenesis imperfecta: a heterogeneous morphologic phenotype in cultured dermal fibroblasts.
abstract: Osteogenesis imperfecta (OI) is a phenotype with clinical and biochemical heterogeneity. We report here that expression of the OI phenotype extends to the level of dermal fibroblast morphology in vitro. Growth characteristics and morphology of control (n = 6) and OI cell strains (n = 10, representing the four major OI categories, Sillence classification) were compared by measuring the following: (i) days required in culture to reach confluence after plating at uniform density; (ii) cell density at confluence; (iii) width and length of cells (measured on phase contrast micrographs at 300 X magnification). Our results show that: (i) OI fibroblasts take longer (11-27 days, mean 20 days) than control cells (10-19 days, mean 16 days) to reach stationary phase; (ii) all OI phenotypes achieve a lower cell density (0.87 X 10(6) cells/P60, range 0.3-1.6 X 10(6] at stationary phase relative to control cells (2.2 X 10(6) cells/P60, range 1.7-2.6 X 10(6); F4,77 = 56.1, p less than 0.01, indicating that OI cells are larger than normal). Cell shape (expressed as the width : length ratio) was also abnormal in OI cells. (F4,730 = 37.6, p less than 0.01), types I and II OI cells have significantly increased ratios (p less than 0.01) relative to control, type III, and type IV cells. Intra-group phenotypic heterogeneity was also apparent in the OI categories and also within the control population. These findings confirm deviant morphologic phenotypes in OI dermal fibroblasts and further demonstrate interindividual heterogeneity in the expression of genes that determine size and shape of dermal fibroblasts in both OI and normal donors.
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D012867:Skin / Q000166:cytology