heparitin-sulfate and Osteogenesis-Imperfecta

In previous work, we compared the steady-state levels of specific matrix components in human bone cells derived from patients with osteogenesis imperfecta (OI) to those of age-matched controls. A remarkable finding was the observation that there was a reduction not only in the total levels of collagen, but also in osteonectin and three proteoglycans (a large chondroitin sulfate proteoglycan, biglycan, and decorin). This pattern was observed in patients with and without detectable collagen defects. More recent analysis of extracellular matrix composition have yielded that, compared with age-matched controls, bone cells from OI patients produced higher steady-state levels of fibronectin and thrombospondin. The percentage of these two proteins incorporated into the cell layer pool was also higher in OI than in age-matched controls. In addition, the steady-state levels of hyaluronan and a heparan sulfate proteoglycan were analyzed in both OI and age-matched controls. Although the total (medium + cell layer) steady-state levels of hyaluronan were reduced by 1/3, the percentage of the hyaluronan in the cell layer pool of patients with OI increased between 100-250% of age-matched control. Thus the matrix elaborated by human OI bone cells is not only quantitatively different but also qualitatively distinct from that of age-matched controls. Not only have specific bone cell matrix components (collagen, osteonectin, the large chondroitin sulfate proteoglycan, biglycan, and decorin) been found to be present in reduced levels in OI bone cells, but some matrix components (thrombospondin, fibronectin, and hyaluronan) have also been found to be present in elevated levels in the matrix of OI cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Biglycan; Cell Adhesion Molecules; Cells, Cultured; Child; Child, Preschool; Chondroitin Sulfates; Collagen; Decorin; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix; Extracellular Matrix Proteins; Female; Fibronectins; Fluorometry; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Infant; Male; Membrane Glycoproteins; Mutation; Osteoblasts; Osteogenesis Imperfecta; Osteonectin; Phenotype; Proteoglycans; Thrombospondins; White People

Topics: Cartilage Diseases; Collagen; Genes, Dominant; Glycosaminoglycans; Heparitin Sulfate; Hip Dislocation, Congenital; Humans; Keratan Sulfate; Mucopolysaccharidosis IV; Osteogenesis Imperfecta; Scoliosis