Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism

J Orthop Res. 2011 Oct;29(10):1585-91. doi: 10.1002/jor.21417. Epub 2011 Mar 29.

Abstract

Tobacco smoking increases the risk of intervertebral disc degeneration (IDD) and back pain, but the mechanisms underlying the adverse effects of smoking are largely unknown. Current hypotheses predict that smoking contributes to IDD indirectly through nicotine-mediated vasoconstriction which limits the exchange of nutrients between the discs and their surroundings. We alternatively hypothesize that direct contact of disc cells, that is, cells in the outermost annulus and those present along fissures in degenerating discs, with the vascular system containing soluble tobacco smoking constituents could perturb normal metabolic activities resulting in IDD. In this study, we tested our hypothesis by comparing the effects of direct exposure of human disc cells to tobacco smoke condensate and nicotine on cell viability and metabolic activity. We showed that smoke condensate, which contains all of the water-soluble compounds inhaled by smokers, exerts greater detrimental effects on human disc cell viability and metabolism than nicotine. Smoke condensate greatly induced an inflammatory response and gene expression of metalloproteinases while reduced active matrix synthesis and expression of matrix structural genes. Therefore, we have demonstrated that disc cell exposure to the constituents of tobacco smoke has negative consequences which have the potential to alter disc matrix homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aggrecans / metabolism
  • Cell Survival / drug effects
  • Collagen Type I / metabolism
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Ganglionic Stimulants / adverse effects*
  • Humans
  • Intervertebral Disc / cytology
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / metabolism
  • Intervertebral Disc Degeneration / etiology*
  • Male
  • Matrix Metalloproteinases / metabolism
  • Middle Aged
  • Nicotine / adverse effects*
  • Smoking / adverse effects*
  • Young Adult

Substances

  • Aggrecans
  • Collagen Type I
  • Ganglionic Stimulants
  • Nicotine
  • Matrix Metalloproteinases
  • Dinoprostone