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. ß

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

“…Exposure to smoke extract also causes a dose-dependent toxicity in AF and NP cells. The disc is shifted to a catabolic profile with decreased expression of aggrecan, collagen, prostaglandin, and anticatabolic factors tissue inhibitor of matrix metalloproteinases and increasing activity of catabolic matrix metalloproteinases (MMPs) and the proinflammatory cytokine IL-1b [63,66,99,102]. Smoking reduces production of aggrecan, a major proteoglycan component of disc matrix, and increases aggrecan cleavage, which diminishes the hydrostatic properties of aggrecan needed to counteract compressive forces [102].…”

Cigarette smoking and musculoskeletal disorders

“…In mice exposed to tobacco smoke by direct inhalation to model long term smoking in humans, both a reduced proteoglycan synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan, within its interglobular domain, were found. Cleavage of aggrecan interglobular domain is extremely detrimental as this results in the loss of the entire glycosaminoglycan attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces 29 .…”

Five-year adjacent-level degenerative changes in patients with single-level disease treated using lumbar total disc replacement with ProDisc-L versus circumferential fusion

“…In a Volvo Award paper, Battié et al 1 showed more lumbar disc degeneration in the spines of identical twins discordant for smoking, "but this effect was small." Vo et al 19 suggested that both nicotine-mediated vasoconstriction and direct contact of outer anulus cells with blood vessels containing soluble tobacco smoking constituents may alter disc matrix homeostasis. In a regression analysis of our data, smoking was not identified as a significant factor for DALD.…”