Spine degeneration in a murine model of chronic human tobacco smokers.
Spine degeneration in a murine model of chronic human tobacco smokers.
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DOI：
10.1016/j.joca.2012.04.010
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发表时间：
2012-08
影响因子：
7
通讯作者：
Vo, N.
中科院分区：
文献类型：
--
作者：
Wang, D.;Nasto, L. A.;Roughley, P.;Leme, A. S.;Houghton, A. M.;Usas, A.;Sowa, G.;Lee, J.;Niedernhofer, L.;Shapiro, S.;Kang, J.;Vo, N.
关键词：
探讨慢性吸烟促进小鼠椎间盘退变（IDD）和椎体退变的机制。将三个月大的C57 BL/6小鼠通过直接吸入暴露于烟草烟雾（5支香烟/天，5天/周，持续6个月）以模拟人类长期吸烟。总光盘蛋白多糖含量（DMMB测定），聚集蛋白聚糖蛋白水解（免疫印迹分析），和细胞衰老（p16 INK 4a免疫组化）进行了分析。蛋白聚糖和胶原合成（35 S-硫酸和3 H-脯氨酸掺入，分别）进行了测量，使用光盘器官型培养。通过微型计算机断层扫描测量椎体膨胀度。烟雾暴露小鼠椎间盘蛋白多糖含量为未暴露对照组的63%，而新的蛋白多糖和胶原合成分别为未暴露对照组的59%和41%。暴露于烟草烟雾显着增加金属蛋白酶介导的蛋白水解圆盘聚集蛋白聚糖在其interglobular域（IGD）。在烟雾暴露的小鼠椎间盘中，细胞衰老增加了两倍。烟雾暴露增加椎体终板孔隙度，这与人类IDD密切相关。这些发现进一步支持烟草烟雾是脊柱退化的一个因素。此外，这些数据提供了一种新的机制见解，表明吸烟诱导的IDD是减少PG合成和增加关键盘细胞外基质蛋白聚集蛋白聚糖降解的结果。聚集蛋白聚糖IGD的切割是极其有害的，因为这导致聚集蛋白聚糖的整个糖胺聚糖附着区的损失，这对于吸引抵消压缩力所必需的水是至关重要的。我们的研究结果表明，识别和抑制特定的金属蛋白酶负责烟雾诱导的聚集蛋白聚糖作为一个潜在的治疗策略，以治疗IDD。
To investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice. Three months old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (5 cigarettes/day, 5 days/week for 6 months) to model long-term smoking in humans. Total disc proteoglycan content (DMMB assay), aggrecan proteolysis (immunobloting analysis), and cellular senescence (p16INK4a immunohistochemistry) were analyzed. Proteoglycan and collagen syntheses (35S-sulfate and 3H-proline incorporation, respectively) were measured using disc organotypic culture. Vertebral osteoporosity was measured by micro-computed tomography. Disc proteoglycan content of smoke-exposed mice was 63% of unexposed control, while new proteoglycan and collagen syntheses were 59% and 41% of those of untreated mice, respectively. Exposure to tobacco smoke dramatically increased metalloproteinase-mediated proteolysis of disc aggrecan within its interglobular domain (IGD). Cellular senescence was elevated two folds in discs of smoke-exposed mice. Smoke exposure increased vertebral endplate porosity, which closely correlates with IDD in humans. These findings further support tobacco smoke as a contributor to spinal degeneration. Furthermore, the data provide a novel mechanistic insight, indicating that smoking-induced IDD is a result of both reduced PG synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan. Cleavage of aggrecan IGD is extremely detrimental as this result in the loss of the entire glycosaminoglycan-attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces. Our results suggest identification and inhibition of specific metalloproteinases responsible for smoke-induced aggrecanolysis as a potential therapeutic strategy to treat IDD.
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影响因子：
3
作者：
HART, LG;DEYO, RA;CHERKIN, DC
通讯作者：
CHERKIN, DC
影响因子：
5.5
作者：
Hoyland, J. A.;Le Maitre, C.;Freemont, A. J.
通讯作者：
Freemont, A. J.
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：
9.6
作者：
AUERBACH, O;GARFINKEL, L
通讯作者：
GARFINKEL, L
影响因子：
3
作者：
BATTIE, MC;VIDEMAN, T;KOSKENVUO, M
通讯作者：
KOSKENVUO, M