Investigating the role of DNA damage in tobacco smoking-induced spine degeneration

Abstract

BACKGROUND CONTEXT Tobacco smoking is a key risk factor for spine degeneration. However, the underlying mechanism by which smoking induces degeneration is not known. Recent studies implicate DNA damage as a cause of spine and intervertebral disc degeneration. Because tobacco smoke contains many genotoxins, we hypothesized that tobacco smoking promotes spine degeneration by inducing cellular DNA damage. PURPOSE To determine if DNA damage plays a causal role in smoking-induced spine degeneration. STUDY DESIGN To compare the effect of chronic tobacco smoke inhalation on intervertebral disc and vertebral bone in normal and DNA repair-deficient mice to determine the contribution of DNA damage to degenerative changes. METHODS Two month-old wild-type (C57BL/6) and DNA repair-deficient Ercc1−/Δ mice were exposed to tobacco smoke by direct inhalation (4 cigarettes/day, 5 days/week for 7 weeks) to model first-hand smoking in humans. Total disc proteoglycan (PG) content (1,9-dimethylmethylene blue assay), PG synthesis (35S-sulfate incorporation assay), aggrecan proteolysis (immunoblotting analysis) and vertebral bone morphology (micro-computed tomography) were measured. RESULTS Exposure of wild-type mice to tobacco smoke led to a 19% increase in vertebral porosity and a 61% decrease in trabecular bone volume. Intervertebral discs of smoke-exposed animals also showed a 2.6-fold decrease in GAG content and a 8.1-fold decrease in new PG synthesis. These smoking-induced degenerative changes were similar but not worse in Ercc1−/Δ mice. CONCLUSIONS Short-term exposure to high levels of primary tobacco smoke inhalation promotes degeneration of vertebral bone and discs. Disc degeneration is primarily driven by reduced synthesis of proteoglycans needed for vertebral cushioning. Degeneration was not exacerbated in congenic DNA repair-deficient mice indicating that DNA damage per se does not have a significant causal role in driving smoke-induced spine degeneration.

Is smoking a risk factor for lumbar disc herniation?

“…The results obtained in experimental studies using animal models and biological studies support the association between smoking and degeneration of intervertebral discs [6,40,41]. Nemoto et al established a rat model of exposure to 8 weeks of smoking and observed that the intervertebral discs of the rats exhibited cracks, tears, and misalignment of the annulus fibrosus [41].…”

“…Nemoto et al established a rat model of exposure to 8 weeks of smoking and observed that the intervertebral discs of the rats exhibited cracks, tears, and misalignment of the annulus fibrosus [41]. Nasto et al exposed wild-type and DNA repair-deficient mice to tobacco smoke by direct inhalation of first-hand smoke by humans and showed that the synthesis of proteoglycans, which plays an essential role on vertebral cushioning, declined sharply in the mice disc [6]. The results of these basic investigations are consistent with the findings of our meta-analysis.…”

“…Cigarette smoking generates toxic substances, which may play a role in degeneration of the disc [6]. A number of epidemiological studies have explored the association between smoking and lumbar disc degeneration.…”

Molecular mechanisms of biological aging in intervertebral discs

“…First, disc degeneration refers to the structural and functional failure of the disc as a result of aberrant, pathological cellular and ECM changes . Disc degeneration may be caused by genetic predisposition, injury, aging, and environmental factors such as smoking, or any combination thereof . Unlike disc aging, disc degeneration is not exclusive to the older population, that is, disc degeneration can be present in a younger person due to injury or faulty genetics .…”

Molecular Mechanisms of Intervertebral Disc Degeneration

“…12 Causes of disc degeneration include aging, injury, genetics, and environmental factors such as smoking, or a combination. [13][14][15][16][17][18][19] IDD is not exclusive to the older population, although the aged population and cases with degenerated disc appear to share similar changes. [18][19][20][21][22] The IVD is one of the first tissues to undergo degeneration in adults, with an average onset in the second decade of life and is known to be influenced by a combination of genetic, biological, aging, and physical chemical changes.…”