chondroitin-sulfates and Growth-Disorders

The primary macrophage growth factor, colony-stimulating factor-1 (CSF-1), is homodimeric and exists in 3 biologically active isoforms: a membrane-spanning, cell-surface glycoprotein (csCSF-1) and secreted glycoprotein (sgCSF-1) and proteoglycan (spCSF-1) isoforms. To investigate the in vivo role of the chondroitin sulfate glycosaminoglycan (GAG) chain of spCSF-1, we created mice that exclusively express, in a normal tissue-specific and developmental manner, either the secreted precursor of spCSF-1 or the corresponding precursor in which the GAG addition site was mutated. The reproductive, hematopoietic tooth eruption and tissue macrophage defects of CSF-1-deficient, osteopetrotic Csf1(op)/Csf1(op) mice were corrected by transgenic expression of the precursors of either sgCSF-1 or spCSF-1. Furthermore, in contrast to the transgene encoding csCSF-1, both failed to completely correct growth retardation, suggesting a role for csCSF-1 in the regulation of body weight. However, spCSF-1, in contrast to sgCSF-1, completely resolved the osteopetrotic phenotype. Furthermore, in transgenic lines expressing different concentrations of sgCSF-1 or spCSF-1, spCSF-1 more efficiently corrected Csf1(op)/Csf1(op) defects of tooth eruption, eyelid opening, macrophage morphology, and B-cell deficiency than sgCSF-1. These results indicate an important role of the CSF-1 chondroitin sulfate proteoglycan in in vivo signaling by secreted CSF-1.

Topics: Animals; B-Lymphocytes; Bone Resorption; Chondroitin Sulfates; Eyelids; Female; Gene Expression Regulation, Developmental; Growth Disorders; Hematopoiesis; Macrophage Colony-Stimulating Factor; Macrophages; Male; Mice; Mice, Mutant Strains; Mice, Transgenic; Mutation; Odontogenesis; Osteopetrosis; Phenotype; Reproduction; Tooth Eruption

Topics: Chondroitin Sulfates; Corneal Opacity; Growth Disorders; Humans; Spine

Topics: Adolescent; Aortic Valve Stenosis; Child; Chondroitin Sulfates; Dental Enamel Hypoplasia; Face; Female; Glycosaminoglycans; Growth Disorders; Humans; Joint Diseases; Male; Syndrome; Voice

Clinical, radiological, histochemical, ultrastructural, and biochemical studies were conducted on three cases of I-cell disease. I-cell disease can be readily distinguished from Hurler syndrome (mucopolysaccharidosis I) by the presence of hypertrophic gums, vacuolated lymphocytes in peripheral blood, and a normal level of urinary mucopolysaccharides. Accumulation of proteoglycans was more prominent in the inclusion bodies of I-cell chondrocytes in comparison to cultured fibroblasts, which contained a large amount of glycolipids and a small amount of proteoglycans. An autosomal recessive mode of inheritance was suggested in two of the cases.

Topics: Abnormalities, Multiple; Cartilage; Child, Preschool; Chondroitin Sulfates; Cytoplasmic Granules; Female; Fibroblasts; Growth Disorders; Humans; Infant; Lipidoses; Lymphocytes; Male; Psychomotor Disorders; Renal Aminoacidurias; Syndrome