title: Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism.
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.
authors: Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. von@upmc.edu
authors: Nam
authors: N
authors: Vo
authors: Dong
authors: D
authors: Wang
authors: Gwendolyn
authors: G
authors: Sowa
authors: William
authors: W
authors: Witt
authors: Kevin
authors: K
authors: Ngo
authors: Paulo
authors: P
authors: Coelho
authors: Ronald
authors: R
authors: Bedison
authors: Barbara
authors: B
authors: Byer
authors: Rebecca
authors: R
authors: Studer
authors: Joon
authors: J
authors: Lee
authors: Y Peter
authors: YP
authors: Di
authors: James
authors: J
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005731:Ganglionic Stimulants / Q000009:adverse effects*; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000209:etiology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D053674:Aggrecans; D024042:Collagen Type I; D005731:Ganglionic Stimulants; D009538:Nicotine; D020782:Matrix Metalloproteinases; D015232:Dinoprostone