title: Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading.
abstract: METHODS
  An in vivo study of the toxic consequences of static compressive stress on the intervertebral disc.
  
  
  OBJECTIVE
  To determine whether disc cell death is correlated with the magnitude and duration of spinal compressive loading.
  
  
  BACKGROUND
  Static compression in vivo has been demonstrated to induce cell death. Cell death, in turn, has been associated with disc degeneration in humans. There are currently no tolerance criteria for the intervertebral disc that combine both biomechanical and biologic factors, although both have been implicated in cases of accelerated degeneration.
  
  
  METHODS
  Mouse tail discs were loaded in vivo with an external compression device. Compressive stress was applied at one of two magnitudes (0.4 and 0.8 MPa) for 7 days, and at one additional magnitude (1.3 MPa) for 1, 3, and 7 days. Midsagittal sections of the discs were stained for apoptosis using the TdT-dUTP terminal nick-end labeling (TUNEL) reaction. Quantal analysis was used to correlate the extent of cell death to the magnitude and duration of loading.
  
  
  RESULTS
  The probit transformation of the percentage of dying cells was proportional to the sum of the logarithmic transformations of the compressive stress and the time of loading.
  
  
  CONCLUSIONS
  The results of this study demonstrate the feasibility of developing a quantitative correlation between spinal loading and disc degeneration. Such a correlation may be coupled in the future to existing engineering models that predict spinal loading in response to physical exposures and lead to improved definition of the bounds of healthy and unhealthy spinal loading, and ultimately, refined guidelines for low back safety.
authors.affiliation: Orthopaedic Bioengineering Laboratory, Department of Orthopaedic Surgery, University of California, San Francisco 94143-0514, USA. jlotz@itsa.ucsf.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Lotz
authors.forename: J R
authors.initials: JR
authors.lastname: Chin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019245:Compressive Strength / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007403:Intervertebral Disc / Q000473:pathology*; D008297:Male; D051379:Mice; D013131:Spine / Q000502:physiology; D013623:Tail; D016474:Weight-Bearing / Q000502:physiology*