title: The effect of nucleus pulposus crosslinking and glycosaminoglycan degradation on disc mechanical function.
abstract: Altered mechanical loading, secondary to biochemical changes in the nucleus pulposus, is a potential mechanism in disc degeneration. An understanding of the role of this altered mechanical loading is only possible by separating the mechanical and biological effects of early nucleus pulposus changes. The objective of this study was to quantify the mechanical effect of decreased glycosaminoglycans (GAG) and increased crosslinking in the nucleus pulposus using in vitro rat lumbar discs. Following initial mechanical testing the discs were injected according to the four treatment groups: PBS control, chondroitinase-ABC (ChABC) for GAG degradation, genipin (Gen) for crosslinking, or a combination of chondroitinase and genipin (ChABC+Gen). After treatment the discs were again mechanically tested, followed by histology or biochemistry. Neutral zone mechanical properties were changed by approximately 20% for PBS, ChABC, and ChABC+Gen treatments (significant only for PBS in a paired comparison). These trends were reversed with genipin crosslinking alone. With ChABC treatment the effective compressive modulus increased and the GAG content decreased; with the combination of ChABC+Gen the mechanics and GAG content were unchanged. Degradation of nucleus pulposus GAG alters disc axial mechanics, potentially contributing to the degenerative cascade. Crosslinking is unlikely to contribute to degeneration, but may be a potential avenue of treatment.
authors.affiliation: Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, Philadelphia, PA 19104-6081, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Yerramalli
authors.forename: A I
authors.initials: AI
authors.lastname: Chou
authors.forename: G J
authors.initials: GJ
authors.lastname: Miller
authors.forename: S B
authors.initials: SB
authors.lastname: Nicoll
authors.forename: K R
authors.initials: KR
authors.lastname: Chin
authors.forename: D M
authors.initials: DM
authors.lastname: Elliott
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D057889:Iridoid Glycosides; D039823:Iridoids / Q000494:pharmacology; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013122:Spinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; D057889:Iridoid Glycosides; D039823:Iridoids; C007834:genipin; D019765:Chondroitin ABC Lyase