Non-enzymatic glycation of annulus fibrosus alters tissue-level failure mechanics in tension
Non-enzymatic glycation of annulus fibrosus alters tissue-level failure mechanics in tension
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纤维环的非酶糖化改变组织水平的张力失效机制
DOI：
10.1016/j.jmbbm.2021.104992
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发表时间：
2022
影响因子：
3.9
通讯作者：
O'Connell, Grace D.
中科院分区：
文献类型：
--
作者：
Werbner, Benjamin;Lee, Matthew;Lee, Allan;Yang, Linda;Habib, Mohamed;Fields, Aaron J.;O'Connell, Grace D.
已知晚期糖基化终产物（AGEs）随着年龄的增长在生物组织中积累，并且在糖尿病和慢性肾脏疾病患者中以加速的速度积累。临床上，糖尿病与背痛的频率和严重程度增加，椎间盘退变加速以及椎间盘突出风险增加有关。尽管有显著的临床证据表明，糖尿病诱导的AGEs可能在椎间盘衰竭中发挥作用，并且大量的先前工作调查AGEs对骨、软骨和肌腱力学的影响，但AGEs对纤维环（AF）失效力学的影响尚未报道。因此，在本发明中，本研究的目的是确定生理水平的AGEs和AF在两种不同的负荷率下的拉伸力学之间的关系。在体外，应用甲基乙二醛处理以最小化组织水合作用的变化，并基于从人AF组织测量的值诱导两种不同水平的AGEs。在体外，糖化使模量增加48-99%，破坏应力增加45-104%。与对照相比，破坏后能量吸收能力降低15-32%（平均值的AN 0 VAp < 0.0001;在两个加载速率和糖化水平上给出范围）。AGE含量与弹性模量（R = 0.74，p < 0.0001）和破坏应力（R = 0.70，p < 0.0001）呈强相关，与破坏后能量吸收能力呈中等相关（R = 0.62，p < 0.0001）。在高糖化水平下，失效应变降低了10-17%（ANOVAp= 0.01）。所有组的组织含水量保持接近或略高于新鲜组织水平。本文报道的糖基化引起的力学改变与其他结缔组织的趋势一致，但不能完全解释糖尿病患者椎间盘突出的临床倾向。这项研究的结果可用于开发先进的计算模型，旨在研究椎间盘疾病的进展，并提供更深入的了解改变的结构-功能关系，可能导致组织功能障碍和衰老和疾病的失败。
Advanced-glycation end products (AGEs) are known to accumulate in biological tissues with age and at an accelerated rate in patients with diabetes and chronic kidney disease. Clinically, diabetes has been linked to increased frequency and severity of back pain, accelerated disc degeneration, and an increased risk of disc herniation. Despite significant clinical evidence suggesting that diabetes-induced AGEs may play a role in intervertebral disc failure and substantial previous work investigating the effects of AGEs on bone, cartilage, and tendon mechanics, the effects of AGEs on annulus fibrosus (AF) failure mechanics have not yet been reported. Thus, the aim of this study was to determine the relationship between physiological levels of AGEs and AF tensile mechanics at two distinct loading rates.In vitroglycation treatments with methylglyoxal were applied to minimize changes in tissue hydration and induce two distinct levels of AGEs based on values measured from human AF tissues.In vitroglycation increased modulus by 48–99% and failure stress by 45–104% versus control and decreased post-failure energy absorption capacity by 15–32% versus control (ANOVAp< 0.0001 on means; range given across two loading rates and glycation levels). AGE content correlated strongly with modulus (R = 0.74,p< 0.0001) and failure stress (R = 0.70,p< 0.0001) and moderately with post-failure energy absorption capacity (R = 0.62,p< 0.0001). Failure strain was reduced by 10–17% at the high-glycation level (ANOVAp= 0.01). Tissue water content remained near or just above fresh-tissue levels for all groups. The alterations in mechanics with glycation reported here are consistent with trends from other connective tissues but do not fully explain the clinical predisposition of diabetics to disc herniation. The results from this study may be used in the development of advanced computational models that aim to study disc disease progression and to provide a deeper understanding of altered structure-function relationships that may lead to tissue dysfunction and failure with aging and disease.