Investigating the role of DNA damage in tobacco smoking-induced spine degeneration.
Investigating the role of DNA damage in tobacco smoking-induced spine degeneration.
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DOI：
10.1016/j.spinee.2013.08.034
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发表时间：
2014-03-01
期刊：
影响因子：
--
通讯作者：
Vo NV
中科院分区：
文献类型：
--
作者：
Nasto LA;Ngo K;Leme AS;Robinson AR;Dong Q;Roughley P;Usas A;Sowa GA;Pola E;Kang J;Niedernhofer LJ;Shapiro S;Vo NV
吸烟是脊柱退变的一个关键危险因素。然而，吸烟诱发变性的潜在机制尚不清楚。最近的研究暗示DNA损伤是脊柱和椎间盘退变的原因。由于烟草烟雾含有许多基因毒素，我们假设吸烟通过诱导细胞DNA损伤来促进脊柱退化。确定DNA损伤是否在吸烟引起的脊柱退变中起因果作用。比较慢性烟草烟雾吸入对正常和DNA修复缺陷小鼠椎间盘和椎骨的影响，以确定DNA损伤对退行性变化的贡献。两个月大的野生型（C57BL/6）和DNA修复缺陷Ercc1−/Δ小鼠通过直接吸入烟草烟雾（4支/天，每周5天，持续7周）来模拟人类的第一手吸烟。测定椎间盘总蛋白多糖（PG）含量（1,9-二甲基亚甲基蓝法）、PG合成（35s硫酸盐结合法）、聚集蛋白水解（免疫印迹法）和椎体骨形态（显微计算机断层扫描法）。野生型小鼠暴露于烟草烟雾中导致椎体孔隙度增加19%，骨小梁体积减少61%。暴露于烟雾中的动物椎间盘也显示出GAG含量下降2.6倍，新PG合成下降8.1倍。这些吸烟引起的退行性改变在Ercc1−/Δ小鼠中相似但并不更糟。短期暴露于高水平的初级烟草烟雾吸入可促进椎体骨和椎间盘退变。椎间盘退变主要是由于椎体缓冲所需的蛋白聚糖合成减少所致。基因DNA修复缺陷小鼠的退行性变没有加剧，这表明DNA损伤本身在驱动烟雾诱导的脊柱退行性变中没有显著的因果作用。
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. To determine if DNA damage plays a causal role in smoking-induced spine degeneration. 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. 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. 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. 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.
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影响因子：
3
作者：
FRYMOYER, JW;POPE, MH;WILDER, DG
通讯作者：
WILDER, DG
影响因子：
3
作者：
HART, LG;DEYO, RA;CHERKIN, DC
通讯作者：
CHERKIN, DC
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
3
作者：
Nasto LA;Seo HY;Robinson AR;Tilstra JS;Clauson CL;Sowa GA;Ngo K;Dong Q;Pola E;Lee JY;Niedernhofer LJ;Kang JD;Robbins PD;Vo NV
通讯作者：
Vo NV
影响因子：
3
作者：
BATTIE, MC;VIDEMAN, T;KOSKENVUO, M
通讯作者：
KOSKENVUO, M