chondroitin and Bone-Diseases

The roles of chondroitin sulfate (CS) and dermatan sulfate (DS) have been demonstrated in various biological events such as the construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, and growth factors. Human genetic diseases, including skeletal abnormalities, connective tissue diseases, and heart defects, were reported to be caused by mutations in the genes encoding glycosyltransferases, epimerases, and sulfotransferases that are responsible for the biosynthesis of CS and DS. Glycobiological approaches revealed that mutations in CS- and DS-biosynthetic enzymes led to reductions in their enzymatic activities and in the levels of CS and DS. Furthermore, CS at the surface of tumor cells plays a key role in pulmonary metastasis. A receptor for advanced glycation end-products (RAGE) was predominantly expressed in the lung, and was identified as a functional receptor for CS chains. CS and anti-RAGE antibodies inhibited the pulmonary metastasis of not only Lewis lung carcinoma but also B16 melanoma cells. Hence, RAGE and CS are potential targets of drug discovery for pulmonary metastasis and a number of other pathological conditions involving RAGE in the pathogenetic mechanism. This review provides an overview of glycobiological studies on characterized genetic disorders caused by the impaired biosynthesis of CS, as well as DS, and on the pulmonary metastasis of Lewis lung carcinoma cells involving CS and RAGE.

Topics: Animals; Bone Diseases; Carcinoma, Lewis Lung; Chondroitin; Dermatan Sulfate; Humans; Lung Neoplasms; Mice; Receptor for Advanced Glycation End Products; Skin Diseases

In order to investigate the involvement of cartilage proteoglycans in the pathogenesis of human congenital skeletal disorders, proteoglycans were extracted with 4 M guanidine HCl from the iliac crest cartilage of children with various skeletal diseases; lysosomal storage diseases (group I), osteochondrodysplasias (group II) and controls (group III). The cartilage-type proteoglycan (PG-H) was purified and its chondroitin sulfate moiety was analyzed by digestion with chondroitinase-ABC. In group II and group III, the relative amounts of the unsaturated disaccharide products changed in an age-related manner; decrease (from 50% to 30%) of delta Di-4S with a compensatory increase (from 40% to 60%) of delta Di-6S with increasing age from 0 to 15 years. On the other hand, some cases in group I showed aberrant composition of the disaccharide products; a lower content of delta Di-4S with a correspondingly higher content of delta Di-6S. Patients in group I have clinically similar skeletal disorders, and the extent of the compositional abnormality seems to reflect the severity of the skeletal disorder. Therefore, one may consider that the aberrant composition of the glycosaminoglycans in PG-H is involved in the pathogenesis of the skeletal disorder of lysosomal storage diseases.

Topics: Adolescent; Bone Diseases; Cartilage; Child; Child, Preschool; Chondroitin; Chondroitin Sulfates; Chromatography, Gel; Female; Humans; Ilium; Infant, Newborn; Male; Metabolism, Inborn Errors; Proteoglycans

Topics: Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Chondroitin; Connective Tissue; Gingival Hypertrophy; Glycosaminoglycans; Histocytochemistry; Humans; Infant; Infant, Newborn; Joint Diseases; Male; Methods; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling; Syndrome

Topics: Adolescent; Adult; Age Factors; Amines; Benzyl Compounds; Bone Diseases; Cartilage; Chondroitin; Female; Hot Temperature; Humans; Knee Injuries; Knee Joint; Male; Middle Aged; Oxidoreductases; Proteins; Synovial Fluid

Topics: Animals; Bone and Bones; Bone Diseases; Bone Neoplasms; Cattle; Chondroitin; Collagen; Glycosaminoglycans; Humans

Topics: Adolescent; Bone Diseases; Child; Chondroitin; Cleidocranial Dysplasia; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Intellectual Disability; Keratins; Male; Mucopolysaccharidoses; Osteitis Deformans; Osteogenesis Imperfecta; Scoliosis

Topics: Adolescent; Body Fluids; Bone Diseases; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Dysostoses; Humans; Urine