keratan-sulfate and Scoliosis

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

Several biomarkers have been used to evaluate osteoarthritis of the limb joints. Here we evaluated the use of serum cartilage metabolites as biomarkers for degenerative lumbar scoliosis (DLS). Fifty-two DLS patients with Cobb angle > 10° were compared with 19 control patients. Serum levels of hyaluronic acid (HA), keratan sulfate (KS), cartilage oligomeric matrix protein (COMP), collagen type II cleavage (C2C), and procollagen type II C-propeptide (CPII) were measured. Serum levels of KS (DLS 1.20 ± 0.44 µg/ml vs. control 0.98 ± 0.33 µg/ml), CPII (DLS 1905.1 ± 948.2 ng/ml vs. control 1223.6 ± 884.4 ng/ml), and C2C (DLS 219.1 ± 59.2 ng/ml vs. control 177.7 ± 71.7 ng/ml) were significantly higher in DLS. There were no significant differences in the levels of HA or COMP. There was a significant positive correlation between the Cobb angle and CPII in DLS. This is the first study to evaluate the cartilage biomarkers in DLS. The results suggest DLS patients have higher levels of type II collagen synthesis and degradation, indicated by elevated serum CPII and C2C, respectively. As type II collagen is a major component of collagens in the nucleus pulposus and facet joint cartilages, its enhanced turnover may be related to the development and progression of DLS.

Topics: Aged; Aged, 80 and over; Biomarkers; Cartilage; Cartilage Oligomeric Matrix Protein; Collagen Type II; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Hyaluronic Acid; Keratan Sulfate; Lumbar Vertebrae; Male; Matrilin Proteins; Middle Aged; Peptide Fragments; Procollagen; Radiography; Scoliosis

Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of the SLRP core protein species present in intervertebral discs with various pathologies.. Eighteen intervertebral discs from patients with scoliosis (n = 7, 19-53 years), degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58 years) were used in this study. Proteoglycans were dissociatively extracted from disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) assessed by Western blotting following deglycosylation with chondroitinase ABC and keratanase.. Intact SLRP core proteins and a number of core protein fragments were identified in most of the discs examined. Biglycan and fibromodulin were the most extensively fragmented. Keratocan generally occurred as two bands, one representing the intact core protein, the other a smaller fragment. The intact core protein of lumican was detected in all samples with fragmentation evident in only one of the older scoliotic discs. Decorin was less obvious in the disc samples and showed little fragmentation.. In this cohort of pathological intervertebral discs, fragmentation of certain SLRP core proteins was common, indicating that some SLRPs are extensively processed during the pathological process. Identification of specific SLRP fragments which correlate with disc pathology may not only help understand their aetiopathogeneses, but also provide biomarkers which can be used to monitor disease progression or to identify particular disc disorders.

Topics: Adult; Biglycan; Chondroitin Sulfate Proteoglycans; Cohort Studies; Decorin; Disease Progression; Extracellular Matrix Proteins; Female; Fibromodulin; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Keratan Sulfate; Leucine; Lumican; Male; Middle Aged; Proteoglycans; Scoliosis

Variation in abundance and structure of chondroadherin (CHAD) were studied in the extracellular matrix (ECM) of scoliotic and normal human discs.. To determine whether CHAD abundance and fragmentation vary between different sides of the scoliotic disc and between scoliotic and normal discs.. Scoliosis involves curvature of the spine including wedging of the intervertebral discs (IVDs), resulting in altered mechanical loading, which can influence cell metabolism and matrix structure in the IVD. A protein such as CHAD that can influence both cell metabolism and ECM organization could influence disc pathology in scoliosis.. IVDs were obtained from patients with scoliosis and from normal individuals. A proteomic analysis was performed to identify molecules that exhibit side-specific variations in abundance. In addition, changes in the abundance and fragmentation of CHAD and other members of the leucine-rich repeat protein family were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Aggrecan fragmentation was used as an indicator of proteinase action.. The relative amount of CHAD was consistently lower on the concave side of the discs in all patients studied. In addition, proteolytic degradation of CHAD occurred in some patients with scoliosis, but not in normal IVDs. The presence of aggrecan fragments provided evidence for both aggrecanase and metalloproteinase activity in the scoliotic discs although no side-specific difference was found. Other members of the leucine-rich repeat family of proteins did not show evidence of the same consistent variation in abundance between the 2 sides and did not show signs of degradation.. As CHAD can interact with both the ECM and the cells, it can provide a mechanism for regulating cell metabolism and ECM structure, and so play a role in promoting matrix homeostasis. Thus, changes in CHAD abundance or structure could be associated with the pathologic changes occurring in the scoliotic IVD.

Topics: Adolescent; Aggrecans; Biglycan; Blotting, Western; Chondroitin Sulfate Proteoglycans; Decorin; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix Proteins; Female; Fibromodulin; Humans; Intervertebral Disc; Keratan Sulfate; Lumican; Male; Mass Spectrometry; Peptide Hydrolases; Proteoglycans; Scoliosis

Comparative ultrastructural study of intervertebral discs from normal subjects and patients with scoliosis.. To identify ultrastructural relations among keratan sulfate (KS) proteoglycan, alpha-elastin, collagen fibers, and elastic fibers in normal and scoliotic discs.. KS proteoglycans, elastic fibers, and collagen fibers play important mechanical roles in the intervertebral disc, but the distributions of KS proteoglycans and elastin in this tissue have received little attention.. Tissues were fixed in 4% paraformaldehyde. Monoclonal antibody 5-D-4 (which recognizes a KS epitope on aggrecan, fibromodulin, and lumican) and polyclonal anti-alpha-elastin were visualized with a 10-nm immunogold-conjugated secondary antibody.. In a normal disc, a regular pattern of KS labeling occurred around collagen fibers, in the cell cytoplasm, and in the rough endoplasmic reticulum; the nucleus pulposus was more densely labeled for KS than was the anulus fibrosus. In scoliotic disc anulus fibrosus, KS labeling was weak throughout the matrix and pericellularly but abundant in lysosomes and on electron-dense material in degenerate cells. Degenerate collagen fibers in scoliotic tissue bore less KS than did normal fibers. KS labeling of the microfibrillar region of elastic fibers was strong in normal disc but weak in scoliotic disc. Elastin labeling of elastic fibers was weaker in scoliotic than in normal tissue.. KS proteoglycans and elastic fibers are closely associated with the lamellar organization of the collagen fibers in a normal disc. In scoliosis, impaired regulation of collagen fibrillogenesis by lumican or fibromodulin may result in disruption of the lamellar structure.

Topics: Adolescent; Adult; Chondroitin Sulfate Proteoglycans; Elastin; Female; Humans; Immunohistochemistry; Intervertebral Disc; Keratan Sulfate; Lumbar Vertebrae; Lumican; Male; Scoliosis

The concentrations of keratan sulfates and unmodified keratan sulfates increased in the vertebral body growth plate in patients with idiopathic scoliosis. Sulfation and acetylation of total glycosaminoglycans decreased by 50 and 30%, respectively. These changes reflect the decrease in biological activity of molecules that modulate function of the growth plate.

Topics: Acetylation; Adolescent; Case-Control Studies; Glycosaminoglycans; Growth Plate; Humans; Keratan Sulfate; Scoliosis; Spine; Thoracic Vertebrae

Topics: Cartilage Diseases; Collagen; Genes, Dominant; Glycosaminoglycans; Heparitin Sulfate; Hip Dislocation, Congenital; Humans; Keratan Sulfate; Mucopolysaccharidosis IV; Osteogenesis Imperfecta; Scoliosis