In situ accumulation of advanced glycation endproducts (AGEs) in bone matrix and its correlation with osteoclastic bone resorption.

In situ accumulation of advanced glycation endproducts (AGEs) in bone matrix and its correlation with osteoclastic bone resorption.
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DOI:
10.1016/j.bone.2011.04.009
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发表时间:
2011-08
期刊:
影响因子:
4.1
通讯作者:
Wang, Xiaodu
Wang, Xiaodu
中科院分区:
医学2区
文献类型:
--
作者:
Dong, X. Neil;Qin, An;Xu, Jiake;Wang, Xiaodu

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晚期糖基化终产物(AGEs)已被观察到随着年龄的增长在骨中积累,并可能对骨吸收活动产生影响。然而,AGEs在骨中积累的潜在机制仍然知之甚少。本研究以年轻(31±6岁)、中年(51±3岁)和老年(76±4岁)三组人类皮质骨标本为研究对象,通过骨片直接培养破骨细胞,测定骨基质中AGEs的时空分布及其对骨吸收活性的影响。本研究结果表明,荧光强度(激发波长360 nm,发射波长470±40 nm)可用于在荧光显微镜下估计骨中AGEs的相对分布(以戊苷为标记物)。利用荧光强度作为AGEs浓度的相对度量,发现AGEs浓度随生物组织年龄的变化而变化,间质组织中AGEs含量最多,旧骨次之,新生骨中AGEs含量最少。此外,AGEs的积累与供体年龄有关,表明供体越年轻,组织中AGEs的积累越少。最有趣的是,AGEs的积累似乎是从水泥线区域开始的,并随着组织老化扩散到其他部位。最后,我们观察到破骨细胞的骨吸收活性与原位AGEs浓度呈正相关,且随供体年龄的增加而增强。这些发现可能有助于阐明AGEs在骨中积累的机制及其与骨重塑过程的关系。
Advanced glycation end products (AGEs) have been observed to accumulate in bone with increasing age and may impose effects on bone resorption activities. However, the underlying mechanism of AGEs accumulation in bone is still poorly understood. In this study, human cortical bone specimens from young (31±6 years old), middle-aged (51±3 years old) and elderly (76±4 years old) groups were examined to determine the spatial-temporal distribution of AGEs in bone matrix and its effect on bone resorption activities by directly culturing osteoclastic cells on bone slices. The results of this study indicated that the fluorescence intensity (excitation wave length 360 nm and emission wave length 470±40 nm) could be used to estimate the relative distribution of AGEs in bone (pentosidine as its marker) under an epifluorescence microscope. Using the fluorescence intensity as the relative measure of AGEs concentration, it was found that the concentration of AGEs varied with biological tissue ages, showing the greatest amount in the interstitial tissue, followed by the old osteons, and the least amount in newly formed osteons. In addition, AGEs accumulation was found to be dependent on donor ages, suggesting that the younger the donor the less AGEs were accumulated in the tissue. Most interestingly, AGEs accumulation appeared to initiate from the region of cement lines, and spread diffusively to the other parts as the tissue aged. Finally, it was observed that the bone resorption activities of osteoclasts were positively correlated with the in situ concentration of AGEs and such an effect was enhanced with increasing donor age. These findings may help elucidate the mechanism of AGEs accumulation in bone and its association with bone remodeling process.
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