keratan-sulfate and Bone-Diseases

Topics: Animals; Bone Diseases; Cartilage; Centrifugation, Density Gradient; Chemical Phenomena; Chemistry; Chondroitin Sulfates; Humans; Hyaluronic Acid; Joint Diseases; Keratan Sulfate; Proteoglycans

We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice.

Topics: Administration, Intravenous; Animals; Animals, Newborn; Bone Diseases; Cartilage; CHO Cells; Chondrocytes; Chondroitinsulfatases; Cricetulus; Disease Models, Animal; Enzyme Replacement Therapy; Growth Plate; Keratan Sulfate; Liver; Mice; Mice, Knockout; Mucopolysaccharidosis IV; Recombinant Proteins; Spleen; Tissue Distribution

Simple methods for the detection of keratan sulphate in urine have been applied to over 300 urine samples collected from children and adults with bone and cartilage dysplasias with or without mental retardation. Abnormal keratan sulphate excretion, which is a feature of type IV mucopolysaccharidosis (Morquio syndrome), is found in patients with that condition only during childhood. Abnormal excretion is also a feature of Kniest dysplasia and GM1 gangliosidosis and may be present in a number of other bone and cartilage dysplasias of unknown aetiology.

Topics: Adolescent; Adult; Bone Diseases; Child; Child, Preschool; Female; Glycosaminoglycans; Humans; Infant; Keratan Sulfate; Male; Middle Aged; Mucopolysaccharidosis IV; Tay-Sachs Disease

Glycosaminoglycan peptides prepared by papain hydrolysis of different regions were obtained from osteoarthrotic and normal human femoral heads. Data obtained in these experiments show that in osteoarthrosis a decrease in keratan sulfate and an increase in chondroitin sulfate are observed. Since keratan sulfate appeared to play an important role in proteoglycan aggregation, we suggest that the keratan sulfate decrease is one of the factors involved in the cartilage disorder observed in patients suffering from osteoarthrosis.

Topics: Aged; Bone Diseases; Cartilage, Articular; Chemical Phenomena; Chemistry; Chondroitin Sulfates; Electrophoresis, Agar Gel; Femur; Glycosaminoglycans; Humans; Joint Diseases; Keratan Sulfate; Middle Aged; Peptides; Proteoglycans