Accumulation of fluorescent advanced glycation end products and carboxymethyl-lysine in human cortical and trabecular bone.
Accumulation of fluorescent advanced glycation end products and carboxymethyl-lysine in human cortical and trabecular bone.
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DOI：
10.1016/j.bonr.2022.101634
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发表时间：
2022-12
期刊：
影响因子：
2.5
通讯作者：
Karim, Lamya
中科院分区：
文献类型：
--
作者：
Vaidya, Rachana;Rezaee, Taraneh;Edwards, Tianna;Bender, Richard;Vickneswaran, Arune;Chalivendra, Vijaya;Karim, Lamya
被称为晚期糖基化终产物（AGEs）的化学交联与骨折风险增加和骨机械性能恶化有关。然而，通过离体和体外方法测量骨AGEs仅限于本体荧光AGEs（fAGEs）和戊糖苷（一种交联荧光AGEs）的定量。然而，发现非交联和非荧光AGE如羧甲基赖氨酸（CML）在量上比戊糖苷高40-100倍，但只有一项先前的研究报道了它在皮质骨中的作用，一项研究报道了它在骨小梁中的作用。在我们的研究中，我们想研究慢性粒细胞白血病的积累是否在皮质和小梁区室不同，以及它们是否与骨机械性能比与fAGEs更密切相关。我们假设CML和fAGEs水平在骨小梁室中较高，并与皮质骨和骨小梁的力学性能呈负相关。我们获得了人尸体皮质骨和骨小梁标本，通过建立体外核糖基化方法诱导AGEs的形成，通过显微计算机断层扫描对标本进行成像，以评估标本的几何形状和微结构，并通过循环参考点压痕和断裂韧性测试对皮质标本进行机械测试，通过压缩测试对骨小梁标本进行机械测试，然后测量fAGEs和CML。与骨小梁（859 ± 317.1 ng Q/mg胶原）相比，皮质骨（687 ± 44.8 ng Q/mg胶原）中的fAGE高22%，而与皮质骨（924.6 ± 576.3 ng/mg蛋白）相比，发现骨小梁（6189.9 ± 866 ng/mg蛋白）中的CML水平高148%。将对照组和核糖组的样本合并，斯皮尔曼相关分析表明CML水平与皮质孔隙度中度相关，而fAGEs则无关（r =+0.505，p ≤ 0.05）和机械性能，如压痕深度皮质骨中的平均能量消耗（r =+0.460，p ≤ 0.05）、总压入深度（r =+0.440，p ≤ 0.05）和平均能量消耗（r =+0.465，p ≤ 0.05）。fAGEs与皮质骨中的裂纹扩展韧性呈负相关趋势（r =-0.365，p = 0.055）。CML与骨小梁的微结构和力学性能之间没有明显的相关性。CML水平也与皮质骨中的fAGEs相关（r =+0.596，p ≤ 0.05），但与松质骨中的fAGEs无关。我们的初步研究结果表明，CML，非交联AGE，可能会影响骨材料和机械性能不同，散装荧光AGEs，鉴于CML在每个骨室的积累。这项研究为未来的研究提供了方向，以分别量化交联和非交联AGEs，因为它们对材料和力学性能的影响可能不同，这将有助于确定更好的生物标志物用于骨强度预测。
Chemical crosslinks known as advanced glycation end-products (AGEs) are associated with increased bone fracture risk and deteriorated bone mechanical properties. However, measurement of bone AGEs via ex vivo and in vitro methods has been limited to quantification of bulk fluorescent AGEs (fAGEs) and pentosidine only, which is a crosslinking fluorescent AGE. However, a non-crosslinking and non-fluorescent AGE such as carboxymethyl-lysine (CML) is found to be 40–100 times higher in quantity than pentosidine, but only one previous study has reported it in cortical bone, and one study reported it in trabecular bone. In our study, we wanted to investigate if accumulation of CML differs in cortical and trabecular compartments and if they are more strongly associated with bone mechanical properties than with fAGEs. We hypothesized that CML and fAGEs level would be higher in the trabecular compartment and show negative correlations to mechanical properties in cortical and trabecular bone. We obtained human cadaveric cortical and trabecular bone specimens, induced the formation of AGEs via the established in vitro ribosylation method, imaged specimens by microcomputed tomography to assess specimen geometry and microarchitecture, and mechanically tested cortical specimens by cyclic reference point indentation and fracture toughness tests and trabecular specimens by compression tests, followed by measurement of fAGEs and CML. fAGEs were 22 % higher in cortical bone (687 ± 44.8 ng Q/mg collagen) compared to trabecular bone (859 ± 317.1 ng Q/mg collagen), whereas CML levels were found to be 148 % higher in trabecular bone (6189.9 ± 866 ng/mg of protein) compared to cortical bone (924.6 ± 576.3 ng/mg of protein). Pooling the specimens from both the control and ribose groups, Spearman correlation analysis indicated that CML levels, but not fAGEs, are moderately associated with cortical porosity (r = +0.505, p ≤ 0.05) and mechanical properties such indentation depth (r = +0.460, p ≤ 0.05), total indentation depth (r = +0.440, p ≤ 0.05), and average energy dissipated (r = +0.465, p ≤ 0.05) in cortical bone. fAGEs showed a trend towards negative association with crack propagation toughness in cortical bone (r = −0.365, p = 0.055). No significant correlations were observed between CML and microarchitecture or mechanical properties in trabecular bone. CML levels were also associated with fAGEs in cortical bone (r = +0.596, p ≤ 0.05) but not in trabecular bone. Our preliminary findings indicate that CML, a non-crosslinking AGE, may affect bone material and mechanical properties differently than bulk fluorescent AGEs, given the higher accumulation of CML in each bone compartment. This study provides direction to future studies to quantify crosslinking and non-crosslinking AGEs separately as their effect on material and mechanical properties may be different and it would help identify better biomarkers for bone strength prediction.
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影响因子：
5.6
作者：
Ban I;Sugawa H;Nagai R
通讯作者：
Nagai R
影响因子：
3.7
作者：
Karim L;Vashishth D
通讯作者：
Vashishth D
影响因子：
4.1
作者：
Karim L;Moulton J;Van Vliet M;Velie K;Robbins A;Malekipour F;Abdeen A;Ayres D;Bouxsein ML
通讯作者：
Bouxsein ML
影响因子：
5.8
作者：
Furst, Jessica R.;Bandeira, Leonardo C.;Rubin, Mishaela R.
通讯作者：
Rubin, Mishaela R.
DOI：
10.4161/derm.22028
发表时间：
2012-07-01
期刊：
Dermato-endocrinology
影响因子：
--
作者：
Gkogkolou P;Böhm M
通讯作者：
Böhm M