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晚期糖基化终产物导致的骨老化:多尺度力学分析

Bone Aging by Advanced Glycation End Products: A Multiscale Mechanical Analysis.

作者信息

Ganeko K, Masaki C, Shibata Y, Mukaibo T, Kondo Y, Nakamoto T, Miyazaki T, Hosokawa R

机构信息

Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Japan.

Division of Biomaterials and Engineering, Department of Conservative Dentistry, Showa University School of Dentistry, Tokyo, Japan.

出版信息

J Dent Res. 2015 Dec;94(12):1684-90. doi: 10.1177/0022034515602214. Epub 2015 Aug 26.

DOI:10.1177/0022034515602214
PMID:26310723
Abstract

The quality and quantity of mandibular bone are essential prerequisites for osseointegrated implants. Only the Hounsfield unit on preoperative computed tomography is currently used as a clinical index. Nevertheless, a considerable mismatch occurs between bone quality and the Hounsfield unit. Loss of bone toughness during aging has been accepted based on empirical evidence, but this concept is unlikely evidence based at the level of mechanical properties. Nonenzymatic bone matrix cross-links associated with advanced glycation end products predominate as a consequence of aging. Thus, loss of tissue integrity could diminish the bone toughening mechanism. Here, we demonstrate an impaired bone toughening mechanism caused by mimicking aging in rabbits on a methionine-rich diet, which enabled an enhanced nonenzymatically cross-linked bone matrix. A 3-point bending test revealed a greater reduction in femoral fracture resistance in rabbits on a methionine-rich diet, despite higher maximum and normalized breaking forces (287.3 N and 88.1%, respectively), than in rabbits on a normal diet (262.2 N and 79.7%, respectively). In situ nanoindentation on mandibular cortical bone obtained from rabbits on a methionine-rich diet did not enable strain rate-dependent stiffening and consequent large-dimensional recovery during rapid loading following constant displacement after a rapid-load indentation test as compared with those in rabbits on a normal diet. Such nanoscale structure-function relationships dictate resistance to cracking propagation at the material level and allow for the overall bone toughening mechanism to operate under large external stressors. The strain-dependent stiffening was likely associated with strain-energy transfer to the superior cross-linked bone matrix network of the normal diet, while the reduction in the enzymatically cross-linked matrix in bone samples from rabbits on a methionine-rich diet likely diminished the intrinsic bone toughening mechanism. The present study also provides a precise protocol for evaluating bone mechanical properties at the material level based on observations from a series of nanoindentation experiments.

摘要

下颌骨的质量和数量是骨整合种植体的基本前提条件。目前,术前计算机断层扫描中的亨氏单位是唯一被用作临床指标的参数。然而,骨质量与亨氏单位之间存在相当大的不匹配。基于经验证据,人们已经接受了衰老过程中骨韧性的丧失,但从力学性能层面来看,这一概念不太可能基于证据。衰老导致与晚期糖基化终末产物相关的非酶促骨基质交联占主导地位。因此,组织完整性的丧失可能会削弱骨强化机制。在此,我们通过在富含蛋氨酸的饮食条件下模拟兔子衰老过程,证明了骨强化机制受损,这种饮食条件会使非酶促交联的骨基质增加。三点弯曲试验显示,尽管富含蛋氨酸饮食组兔子的最大和标准化断裂力更高(分别为287.3 N和88.1%),但其股骨骨折抵抗力的降低幅度大于正常饮食组兔子(分别为262.2 N和79.7%)。与正常饮食组兔子相比,对富含蛋氨酸饮食组兔子下颌皮质骨进行的原位纳米压痕试验显示,在快速加载压痕试验后恒定位移后的快速加载过程中,其无法实现应变率依赖性硬化以及随之而来的大尺寸恢复。这种纳米级的结构 - 功能关系决定了材料层面抵抗裂纹扩展的能力,并使整体骨强化机制在大的外部应力下发挥作用。应变依赖性硬化可能与应变能转移到正常饮食组的高级交联骨基质网络有关,而富含蛋氨酸饮食组兔子骨样本中酶促交联基质的减少可能削弱了内在的骨强化机制。本研究还基于一系列纳米压痕实验的观察结果,提供了一种在材料层面评估骨力学性能的精确方案。

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