Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes.
Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes.
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DOI：
10.1002/jor.22807
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发表时间：
2015-05
影响因子：
2.8
通讯作者：
Lotz, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Fields, Aaron J.;Berg-Johansen, Britta;Metz, Lionel N.;Miller, Stephanie;La, Brandan;Liebenberg, Ellen C.;Coughlin, Dezba G.;Graham, James L.;Stanhope, Kimber L.;Havel, Peter J.;Lotz, Jeffrey C.
关键词：
2型糖尿病（T2D）对许多组织都有不良影响，糖尿病患者椎间盘源性腰痛的发生率较高，表明椎间盘也受到影响。利用多基因肥胖T2D大鼠模型，我们证明糖尿病损害了椎间盘组成、基质稳态和生物力学行为的几个方面。采集6月龄瘦型sd大鼠、肥胖型sd大鼠和糖尿病肥胖型UCD-T2DM大鼠（糖尿病69±7天）的尾骨运动节段。研究结果表明，糖尿病而非肥胖降低了椎间盘糖胺聚糖和水分含量，这些退行性变化与椎体终板厚度增加、终板孔隙度减少以及晚期糖基化终产物（AGE）戊苷水平升高有关。与糖胺聚糖和水分含量减少以及AGE水平升高相一致，糖尿病大鼠椎间盘在压缩时更硬，蠕变更小。在基质水平上，糖尿病大鼠椎间盘中缺氧诱导基因和分解代谢标志物的表达升高与氧化应激增加以及AGEs与其受体之一（RAGE）之间的相互作用增强相一致。综上所述，这些发现表明终板硬化、氧化应激增加和AGE/ rage介导的相互作用可能是解释t2dm椎间盘病理发生率较高的重要因素。
Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end-product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia-inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress and AGE/RAGE-mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D.
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影响因子：
3
作者：
Freedman MK;Hilibrand AS;Blood EA;Zhao W;Albert TJ;Vaccaro AR;Oleson CV;Morgan TS;Weinstein JN
通讯作者：
Weinstein JN
影响因子：
3
作者：
Benneker, LM;Heini, PF;Ito, K
通讯作者：
Ito, K
影响因子：
--
作者：
Loeser, RF;Yammani, R;Yan, SD
通讯作者：
Yan, SD
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
查看双重：比较双层和单层椎骨终结之间的微观结构，生物力学功能和相邻的椎间盘健康。
影响因子：
3
作者：
Fields AJ;Sahli F;Rodriguez AG;Lotz JC
通讯作者：
Lotz JC