title: Spinal biomechanics and aging are major determinants of the proteoglycan metabolism of intervertebral disc cells.
abstract: METHODS
  The proteoglycan metabolism of ovine disc nucleus pulposus and anulus fibrosus cells was investigated in relation to age, spinal level, and intrinsic spinal biomechanical properties.
  
  
  OBJECTIVE
  To evaluate the hypothesis that with aging loss of proteoglycans from the lumbosacral disc exceeds that from upper lumbar discs because of its proximity to a rigid segment, the sacrum.
  
  
  BACKGROUND
  The proteoglycan and associated water of the disc decreases with aging.
  
  
  METHODS
  Proteoglycans were extracted directly from the disc tissues using 4 M GuHCl and examined by composite agarose polyacrylamide gel electrophoresis. Disc cells were cultured in alginate beads, and their metabolic activity was assessed by 3H-thymidine incorporation into DNA and by bioreduction of a cell proliferation dye. Newly synthesized proteoglycans were radiolabeled with 35S, and their molecular weight distributions and ability to aggregate with hyaluronan were determined by Sephacryl S1000 gel chromatography. Resident proteoglycans extracted from disc tissues with 4 M GuHCl were similarly evaluated. A group of adult animals also were studied biomechanically to evaluate the range of spinal motion (L4/L5 to L7/S1).
  
  
  RESULTS
  In contrast to the neonatal proteoglycan samples, the biosynthesis of proteoglycans by nucleus pulposus cells of adult discs increased progressively toward the sacrum. This correlated with increased metabolic activity. Analysis of the resident proteoglycans by composite agarose polyacrylamide gel electrophoresis indicated that although the aggrecan-1 population was present almost exclusively in the neonatal group, it was the aggrecan-2 population that predominated in the adult discs, and it became progressively more heterogeneous with aging and proximity of the disc to the sacrum.
  
  
  CONCLUSIONS
  The proteoglycans of the lumbosacral disc of adult animals turned over faster than proteoglycans of adjacent lumbar discs. The reduced proteoglycan content and ability to aggregate, particularly in the nucleus pulposus of lumbosacral discs, indicated that proteoglycan catabolism exceeded the rate of biosynthesis. These events in the lumbosacral disc are thought to be determined mechanically by its proximity to the sacrum.
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories, The Institute of Bone and Joint Research, The University of Sydney (Dept of Surgery), The Royal North Shore Hospital, Sydney, St. Leonards, New South Wales, Australia.
authors.forename: T K
authors.initials: TK
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Melrose
authors.forename: D
authors.initials: D
authors.lastname: Burkhardt
authors.forename: P
authors.initials: P
authors.lastname: Ghosh
authors.forename: L E
authors.initials: LE
authors.lastname: Claes
authors.forename: A
authors.initials: A
authors.lastname: Kettler
authors.forename: H J
authors.initials: HJ
authors.lastname: Wilke
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001696:Biomechanical Phenomena; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D016059:Range of Motion, Articular / Q000502:physiology; D012447:Sacrum / Q000166:cytology / Q000378:metabolism; D012756:Sheep; D013131:Spine / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D011509:Proteoglycans