Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice.
Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice.
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DOI：
10.1371/journal.pone.0154700
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Vashishth D
中科院分区：
文献类型：
--
作者：
Rubin MR;Paschalis EP;Poundarik A;Sroga GE;McMahon DJ;Gamsjaeger S;Klaushofer K;Vashishth D
骨折，特别是下肢和髋部骨折，是糖尿病的并发症。在1型糖尿病（T1 D）和2型糖尿病（T2 D）中，骨折风险不成比例地比骨矿物质密度测量预测的更差。虽然这种差异的解释是有机基质异常的存在，但尚未完全阐明晚期糖基化终产物（AGEs）如何在宏观和微观水平上与骨退化相关。我们假设骨骼AGE水平（通过特定解剖位置的拉曼显微光谱测定）与骨骼宏观和微观特性之间存在关系，分别通过裂纹生长和显微压痕的生物力学测量证明。我们发现，在OVE 26小鼠（严重早发性T1 D的转基因模型）中，拉曼增加了骨膜表面的AGEs（羧甲基赖氨酸[CML]野生型（WT）：0.0143 ±0.0005 vs T1 D：0.0175 ±0.0002，p = 0.003）。通过断裂力学（扩展韧性WT：4.73 ± 0.32 vs T1 D：3.39 ± 0.24 NM/m1/2，p = 0.010）和参考点压痕（压痕距离增加WT：6.85 ± 0.44 vs T1 D：9.04 ± 0.77 μm; p = 0.043），这些差异与T1 D中较低的骨韧性相关。在T1 D内，通过拉曼测定的较高AGEs与宏观骨韧性呈负相关。这些数据增加了现有的知识体系有关AGEs和骨骼AGEs与生物力学指标之间的关系。
Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices.