keratan-sulfate and Bone-Diseases--Developmental

Topics: Age of Onset; beta-Galactosidase; Bone Diseases, Developmental; Bone Marrow Examination; Diagnosis, Differential; Facial Bones; Female; Gangliosidosis, GM1; Glycosaminoglycans; Humans; Infant; Keratan Sulfate; Kyphosis; Leukocytes; Mucolipidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis IV; Odontoid Process; Pedigree; Scoliosis

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders.

Topics: Animals; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Developmental; Chondrocytes; Disease Models, Animal; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Keratan Sulfate; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucopolysaccharidoses; Spinal Canal; X-Ray Microtomography

Chondro-osseous tissue from four patients with the Kniest dysplasia was studied histochemically using a new plastic embedding technique. Extensive vacuolar changes were observed p--1 throughout the endochondral growth plate and adjacent resting cartilage. These changes occurred within the cartilage matrix and also in the lacunae of degenerating chrondrocytes. The septa of the lesions contained chondroitin sulfate, but little keratan sulfate or collagen. Resting cartilage not adjacent to the growth plate stained irregularly and showed few of the vacuolar lesions, and chondrocytes were enlarged and contained cytoplasic inclusions, but no vacuolar material. Thus, there appears to be a sequence of events initiated by cellular accumulation of a substance and progressing to cellular and matrix degeneration.

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases, Developmental; Cartilage; Cartilage Diseases; Child; Chondroitin Sulfates; Collagen; Female; Humans; Hypertrophy; Keratan Sulfate; Proteoglycans; Syndrome

Topics: Adolescent; Bone and Bones; Bone Diseases, Developmental; Calcium; Cartilage; Cartilage Diseases; Child; Chondroitin; Chondroitin Sulfates; Collagen; Female; Glycosaminoglycans; Histocytochemistry; Humans; Keratan Sulfate

The roentgenographic and clinical findings are described in a mother and daughter with the Kniest syndrome associated with urinary keratan sulfate excretion. Osteoporosis, kyphoscoliosis, vertebral irregularity, pelvic deformity, flat femoral heads and enlargement of the ends of the long bones were the main roentgen findings. Irregularity of ossification on both sides of the growth plate was observed in the daughter, and marked degenerative changes were superimposed on several of the mother's abnormal joints. Abnormal mucopolysacchariduria, observed in both patients, and cataracts, fusion of the symphysis pubis, and deficiency of carpal bones, seen in the mother, have not been described previously.

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases, Developmental; Dwarfism; Female; Foot; Glycosaminoglycans; Hand; Humans; Keratan Sulfate; Mucopolysaccharidoses; Pelvis; Radiography; Syndrome; Wrist