title: Complex loading affects intervertebral disc mechanics and biology.
abstract: BACKGROUND
  Complex loading develops in multiple spinal motions and in the case of hyperflexion is known to cause intervertebral disc (IVD) injury. Few studies have examined the interacting biologic and structural alterations associated with potentially injurious complex loading, which may be an important contributor to chronic progressive degeneration.
  
  
  OBJECTIVE
  This study tested the hypothesis that low magnitudes of axial compression loading applied asymmetrically can induce IVD injury affecting cellular and structural responses in a large animal IVD ex-vivo model.
  
  
  METHODS
  Bovine caudal IVDs were assigned to either a control or wedge group (15°) and placed in organ culture for 7 days under static 0.2MPa load. IVD tissue and cellular responses were assessed through confined compression, qRT-PCR, histology and structural and compositional measurements, including Western blot for aggrecan degradation products.
  
  
  RESULTS
  Complex loading via asymmetric compression induced cell death, an increase in caspase-3 staining (apoptosis), a loss of aggrecan and an increase in aggregate modulus in the concave annulus fibrosis. While an up-regulation of MMP-1, ADAMTS4, IL-1β, and IL-6 mRNA, and a reduced aggregate modulus were induced in the convex annulus.
  
  
  CONCLUSIONS
  Asymmetric compression had direct deleterious effects on both tissue and cells, suggesting an injurious loading regime that could lead to a degenerative cascade, including cell death, the production of inflammatory mediators, and a shift towards catabolism. This explant model is useful to assess how injurious mechanical loading affects the cellular response which may contribute to the progression of degenerative changes in large animal IVDs, and results suggest that interventions should address inflammation, apoptosis, and lamellar integrity.
authors.affiliation: College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Walter
authors.forename: C L
authors.initials: CL
authors.lastname: Korecki
authors.forename: D
authors.initials: D
authors.lastname: Purmessur
authors.forename: P J
authors.initials: PJ
authors.lastname: Roughley
authors.forename: A J
authors.initials: AJ
authors.lastname: Michalek
authors.forename: J C
authors.initials: JC
authors.lastname: Iatridis
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007403:Intervertebral Disc / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013122:Spinal Diseases / Q000378:metabolism / Q000503:physiopathology*; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D053674:Aggrecans; D053583:Interleukin-1beta; D015850:Interleukin-6; D053148:Caspase 3; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D020781:Matrix Metalloproteinase 1; D000071121:ADAMTS4 Protein