title: Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen perturbations in cartilage of Morquio syndrome A patients.
abstract: OBJECTIVE
  To investigate extracellular matrix (ECM) characteristics of cortical bone and articular cartilage of patients with Morquio syndrome A, a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase.
  
  
  METHODS
  Cartilage, bone, and fibroblasts from 2 unrelated patients with Morquio syndrome were used. Histological analysis on bone and cartilage was carried out by means of light and electron microscopy. Lysyl hydroxylation and cross-linking of collagen present in bone, cartilage, and fibroblast cultures was determined by reverse-phase high performance liquid chromatography.
  
  
  RESULTS
  No histological or biochemical differences were seen in cortical bone; furthermore, no differences were seen in the amount and modification of collagen deposited by fibroblasts. Articular cartilage showed major differences: collagen fibrils show a wider range of fibril diameter, the fibrils are in mean thicker, the lysyl hydroxylation level of the triple helix is strongly decreased, the total amount of pyridinolines is in the lower ranges, and the ratio hydroxylysylpyridinoline to lysylpyridinoline is decreased. Changes were also observed with respect to the arrangement of proteoglycans in the extracellular matrix surrounding the chondrocytes.
  
  
  CONCLUSIONS
  The collagen of bone and the collagen deposited by fibroblasts is normal, whereas the ECM of cartilage in Morquio syndrome A patients is affected. Thus, deficiency in N-acetylgalactosamine-6-sulfate sulfatase has an impact on the phenotypic properties of chondrocytes, resulting in the formation of cartilage that is more prone to degeneration, being an explanation for the occurrence of osteoarthritis in Morquio syndrome A patients at early age.
authors.affiliation: Stem Cell & Tissue Engineering Research Group, Medical Biology Section, Department of Pathology & Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Bank
authors.forename: Johanna E M
authors.initials: JE
authors.lastname: Groener
authors.forename: Justus J
authors.initials: JJ
authors.lastname: van Gemund
authors.forename: Petra D
authors.initials: PD
authors.lastname: Maaswinkel
authors.forename: Kees A
authors.initials: KA
authors.lastname: Hoeben
authors.forename: Herman A
authors.initials: HA
authors.lastname: Schut
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
mesh_terms: D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000473:pathology / Q000648:ultrastructure; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D002675:Child, Preschool; D019902:Chondrocytes / Q000473:pathology / Q000648:ultrastructure; D002811:Chondroitinsulfatases / Q000172:deficiency* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008239:Lysine / Q000378:metabolism; D009085:Mucopolysaccharidosis IV / Q000201:enzymology* / Q000473:pathology*
chemical_list: D003432:Cross-Linking Reagents; D003094:Collagen; D002811:Chondroitinsulfatases; C102295:GALNS protein, human; D008239:Lysine