Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs.
Dietary advanced glycation end-product consumption leads to mechanical stiffening of murine intervertebral discs.
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饮食中晚期糖基化终产物的消耗导致小鼠椎间盘机械硬化。
DOI：
10.1242/dmm.036012
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发表时间：
2018-12-18
影响因子：
4.3
通讯作者：
Illien-Jünger S
中科院分区：
文献类型：
--
作者：
Krishnamoorthy D;Hoy RC;Natelson DM;Torre OM;Laudier DM;Iatridis JC;Illien-Jünger S
背部疼痛是致残的主要原因，与椎间盘退变密切相关。减少IVD变性的结构破坏和分解代谢仍然是一个重要的临床挑战。促氧化剂和结构修饰的晚期糖基化终产物（AGEs）会导致肥胖和糖尿病，这与背部疼痛的增加有关，并会因高血糖或摄入高温加工的食物而在组织中积累。富含胶原蛋白的ivd由于其代谢速率较慢，特别容易积累AGE，但尚不清楚饮食中的AGE是否可以穿过终板在ivd中积累。一个饮食小鼠模型被用来验证长期食用高ages饮食导致性别特异性IVD结构破坏和功能改变的假设。高AGE饮食导致IVD的AGE积累，增加IVD的压缩刚度、扭矩范围和失效扭矩，特别是对女性。通过多光子成像测量，这些生物力学变化可能是由纤维环中AGE交联显著增加引起的。胶原杂交肽测量的胶原损伤增加似乎不会影响生物力学特性，随着这些动物年龄的增长，可能是一个危险因素。高ages饮食对女性的更大影响是未来研究的一个重要领域，可能涉及已知与雌激素相互作用的AGE受体。我们得出结论，高ages饮食可能是IVD交联和胶原蛋白损伤的来源，而胶原蛋白损伤是IVD变性的重要因素。饮食调整和干预措施减少AGEs值得进一步研究，对糖尿病患者尤其重要，因为糖尿病患者的AGEs积累更快。摘要：膳食AGEs导致性别特异性的椎间盘结构和功能改变，可能是促进脊柱健康的靶点，尤其是糖尿病患者，AGEs形成迅速。
Back pain is a leading cause of disability and is strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) contribute to obesity and diabetes, which are associated with increased back pain, and accumulate in tissues due to hyperglycemia or ingestion of foods processed at high heat. Collagen-rich IVDs are particularly susceptible to AGE accumulation due to their slow metabolic rates, yet it is unclear whether dietary AGEs can cross the endplates to accumulate in IVDs. A dietary mouse model was used to test the hypothesis that chronic consumption of high AGE diets results in sex-specific IVD structural disruption and functional changes. High AGE diet resulted in AGE accumulation in IVDs and increased IVD compressive stiffness, torque range and failure torque, particularly for females. These biomechanical changes were likely caused by significantly increased AGE crosslinking in the annulus fibrosus, measured by multiphoton imaging. Increased collagen damage measured with collagen hybridizing peptide did not appear to influence biomechanical properties and may be a risk factor as these animals age. The greater influence of high AGE diet on females is an important area of future investigation that may involve AGE receptors known to interact with estrogen. We conclude that high AGE diets can be a source for IVD crosslinking and collagen damage known to be important in IVD degeneration. Dietary modifications and interventions that reduce AGEs warrant further investigation and may be particularly important for diabetics, in whom AGEs accumulate more rapidly. Summary: Dietary AGEs lead to sex-specific intervertebral disc structural and functional changes and may be targeted for promoting spinal health, especially in diabetes, in which AGEs form rapidly.
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影响因子：
2.8
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.
通讯作者：
Lotz, Jeffrey C.
影响因子：
3.7
作者：
Illien-Jünger S;Lu Y;Qureshi SA;Hecht AC;Cai W;Vlassara H;Striker GE;Iatridis JC
通讯作者：
Iatridis JC
影响因子：
2.3
作者：
Jakoi AM;Pannu G;D'Oro A;Buser Z;Pham MH;Patel NN;Hsieh PC;Liu JC;Acosta FL;Hah R;Wang JC
通讯作者：
Wang JC
影响因子：
6.9
作者：
Bourne, Jonathan W.;Lippell, Jared M.;Torzilli, Peter A.
通讯作者：
Torzilli, Peter A.
影响因子：
7.7
作者：
He, CJ;Sabol, J;Vlassara, H
通讯作者：
Vlassara, H