The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone.
The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone.
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DOI：
10.1302/2046-3758.71.bjr-2017-0135.r1
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发表时间：
2018-01
影响因子：
4.6
通讯作者：
Tang SY
中科院分区：
文献类型：
--
作者：
Abar O;Dharmar S;Tang SY
晚期糖基化终产物（AGEs）是胶原蛋白的翻译后修饰，由于还原糖（如葡萄糖）的存在，在骨骼基质中自发形成。AGEs的积累导致胶原蛋白交联，这对骨质量产生不利影响，并已被证明在骨折风险中起主要作用。因此，干预AGEs的形成和积累可能是保护骨质量的可行方法。采用体外模型研究了两种AGE抑制剂氨基胍（AG）和吡哆胺（PM）对老化人皮质骨的作用。从女性尸体（n = 20，年龄范围：57岁至97岁）中获得胫骨中段骨干皮质骨段，并随机接受4种处理之一：对照;仅葡萄糖;葡萄糖和AG;或葡萄糖和PM。治疗后，每个标本进行力学测试，在生理条件下通过参考点压痕，和AGEs定量荧光。通过双向方差分析（ANOVA），用AG和PM处理显示出与对照组相比AGE含量的显著降低，以及压痕距离变化的显著降低，压痕距离是用于分析骨强度的可靠参数（p < 0.05）。这些数据表明，AG和PM防止AGE的形成和随后的生物力学降解体外。AGEs的调节可能有助于确定新的治疗靶点，以减轻骨质量恶化，特别是由于衰老和AGEs易感人群（如糖尿病患者）的恶化。引用此文章：O. Abar，S. Dharmar，S. Y.唐氨基胍（AG）和吡哆胺（PM）对老化人皮质骨的影响。骨关节研究2018;7：105-110。DOI：10.1302/2046-3758.71.BJR-2017-0135.R1。
Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality. An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence. Treatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05). The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics). Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1.