Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism. J Orthop Res

Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Journal of Orthopaedic Research (Impact Factor: 2.99). 10/2011; 29(10):1585-91. DOI: 10.1002/jor.21417
Source: PubMed


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.

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    • "Aging has been found to promote the degradation of structural proteins, thus affecting IL-18 expression in tuberculous disc tissue. Cigarette smoking attenuates effector cytokine responses, alters disc matrix homeostasis, and impairs mycobacterial containment within infected human macrophages [42], [43]. Our research demonstrated that smoking habits were positively correlated with the mRNA levels of IL-17 and negatively correlated with the mRNA levels of IL-10 in the TB group. "
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    ABSTRACT: Objectives The purpose of the present study was to simultaneously examine the transcript levels of a large number of interleukins (ILs; IL-9, IL-10, IL-12, IL-13, IL-16, IL-17, IL-18, IL-26, and IL-27) and investigate their correlation with the clinicopathological profiles of patients with tuberculous intervertebral discs. Methods Clinical data were collected from 150 patients participating in the study from January 2013 to December 2013. mRNA expression levels in 70 tuberculous, 70 herniated, and 10 control intervertebral disc specimens were determined by real-time polymerase chain reaction. Results IL-10, IL-16, IL-17, IL-18, and IL-27 displayed stronger expression in tuberculous spinal disc tissue than in normal intervertebral disc tissue (P<0.05). Our results illustrated multiple correlations among IL-10, IL-16, IL-17, IL-18, and IL-27 mRNA expression in tuberculous samples. Smoking habits were found to have a positive correlation with IL-17 transcript levels and a negative correlation with IL-10 transcript levels (P<0.05). Pain intensity, symptom duration, C-reactive protein levels, and the erythrocyte sedimentation rate exhibited multiple correlations with the transcript levels of several ILs (P<0.05). Conclusions The experimental data imply a double-sided effect on the activity of ILs in tuberculous spinal intervertebral discs, suggesting that they may be involved in intervertebral discs destruction. Our findings also suggest that smoking may affect the intervertebral discs destruction process of spinal tuberculosis. However, further studies are necessary to elucidate the exact role of ILs in the intervertebral discs destruction process of spinal tuberculosis.
    PLoS ONE 06/2014; 9(6):e101324. DOI:10.1371/journal.pone.0101324 · 3.23 Impact Factor
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    • "Among smoking-disconcordant adult twins, smoking explained only 2% of the variance in lumbar DD, which can be regarded as a marginal effect [10,44]. However, in experimental studies, smoking has indisputably caused degenerative changes in the intervertebral discs [6,7,45]. It may well be that the association between smoking and DD can be observed more easily in a young population. "
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    ABSTRACT: The role of environmental factors in lumbar intervertebral disc degeneration (DD) in young adults is largely unknown. Therefore, we investigated whether body mass index (BMI), smoking, and physical activity are associated with lumbar DD among young adults. The Oulu Back Study (OBS) is a subpopulation of the 1986 Northern Finland Birth Cohort (NFBC 1986) and it originally included 2,969 children. The OBS subjects received a postal questionnaire, and those who responded (N = 1,987) were invited to the physical examination. The participants (N = 874) were invited to lumbar MRI study. A total of 558 young adults (325 females and 233 males) underwent MRI that used a 1.5-T scanner at the mean age of 21. Each lumbar intervertebral disc was graded as normal (0), mildly (1), moderately (2), or severely (3) degenerated. We calculated a sum score of the lumbar DD, and analyzed the associations between environmental risk factors (smoking, physical activity and weight-related factors assessed at 16 and 19 years) and DD using ordinal logistic regression, the results being expressed as cumulative odds ratios (COR). All analyses were stratified by gender. Of the 558 subjects, 256 (46%) had no DD, 117 (21%) had sum score of one, 93 (17%) sum score of two, and 92 (17%) sum score of three or higher. In the multivariate ordinal logistic regression model, BMI at 16 years (highest vs. lowest quartile) was associated with DD sum score among males (COR 2.35; 95% CI 1.19-4.65) but not among females (COR 1.29; 95% CI 0.72-2.32). Smoking of at least four pack-years was associated with DD among males, but not among females (COR 2.41; 95% CI 0.99-5.86 and 1.59; 95% 0.67-3.76, respectively). Self-reported physical activity was not associated with DD. High BMI at 16 years was associated with lumbar DD at 21 years among young males but not among females. High pack-years of smoking showed a comparable association in males, while physical activity had no association with DD in either gender. These results suggest that environmental factors are associated with DD among young males.
    BMC Musculoskeletal Disorders 03/2013; 14(1):87. DOI:10.1186/1471-2474-14-87 · 1.72 Impact Factor
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    01/2012; S6:in press. DOI:10.4172/2155-9899.S6-003
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