chondroitin-sulfates 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

The content and composition of glycosaminoglycans in the tubular bones of osteogenesis imperfecta were compared to those in the tubular bones of age-matched controls. Chondroitin sulfate was the major glycosaminoglycan (70-80% of total) both in the normal and pathological bones, and its level, based on the tissue wet weight, was slightly less in the pathological bones. The composition of chondroitin sulfate disaccharide units in the pathological samples was different from those of the control; a lower proportion of chondroitin 4-sulfate unit. Hyaluronate accounted for at most 7% of total glycosaminoglycans from the normal bones. The hyaluronate content of the pathological bones was 1.5- to 3-fold higher than that of the controls. Glycosaminoglycans have been shown to participate in the formation of a functional supramolecular complex in extracellular matrices. Therefore, it may be postulated that the abnormalities in glycosaminoglycan composition in the tubular bones of osteogenesis imperfecta is implicated in some clinical aspects of this connective tissue disorder such as the bony fragility.

Topics: Bone and Bones; Child; Chondroitin Sulfates; Dermatan Sulfate; Humans; Hyaluronic Acid; Male; Osteogenesis Imperfecta

Epiphyseal cartilage and bone tissue from two cases of osteogenesis imperfecta congenita and one control case with similar skeletal age were examined regarding their glycosaminoglycan content. The diseased bone tissue showed a 3-fold increase in glycosaminoglycans, and 20-25 per cent of the chondroitin sulphate disaccharides seemed to be disulphated. The diseased cartilages showed only traces of material with characteristics of disulphates disaccharides. No disulphates disaccharides were isolated from the control materials. No difference between diseased and control material was indicated regarding molecular size, chondroitin-4-sulphate/chondroitin-6-sulphate ratio or contents of keratan sulphate and hyaluronic acid. The disease is thus associated with fundamental changes of the glycosaminoglycan structure, and these changes may be of functional importance to the mineralization process as well as to the organisation of collagen.

Topics: Bone and Bones; Cartilage; Chondroitin Sulfates; Disaccharides; Glycosaminoglycans; Hexosamines; Humans; Infant, Newborn; Osteogenesis Imperfecta; Uronic Acids