Mass spectrometric quantitation of AGEs and enzymatic crosslinks in human cancellous bone.

Mass spectrometric quantitation of AGEs and enzymatic crosslinks in human cancellous bone.
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DOI:
10.1038/s41598-020-75923-8
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发表时间:
2020-11-02
期刊:
影响因子:
4.6
通讯作者:
Saito M
Saito M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Arakawa S;Suzuki R;Kurosaka D;Ikeda R;Hayashi H;Kayama T;Ohno RI;Nagai R;Marumo K;Saito M

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晚期糖基化终产物(AGEs)使骨强度恶化。在40多个物种在体内鉴定,由于技术上的困难,除了戊糖苷的AGEs粗略估计为总荧光AGEs(tfAGEs)。使用LC-QqTOF-MS,我们建立了一个系统,使五个AGEs(CML,CEL,MG-H1,CMA和pentosidine)以及两个成熟和三个未成熟的酶交联定量。从149例接受全膝关节置换术的患者中收集人骨样本。收集他们的临床参数,以研究可能预测AGE蓄积的参数。所有的分析物进行定量,并显示出显着的线性,具有较高的灵敏度和精密度。结果表明,MG-H1是丰度最高的AGE,而戊糖苷的丰度是其他四种AGE的1/200-1/20。AGEs与戊糖苷呈显著强相关,与tfAGEs呈中度相关。多元线性回归分析显示,性别对AGEs的累积贡献最大,其次是年龄、抗酒石酸酸性磷酸酶-5b和HbA 1c。此外,AGEs与未成熟交联呈负相关。AGEs和酶交联的质谱定量对于更好地理解衰老和疾病相关的骨强度退化至关重要。
Advanced glycation end-products (AGEs) deteriorate bone strength. Among over 40 species identified in vivo, AGEs other than pentosidine were roughly estimated as total fluorescent AGEs (tfAGEs) due to technical difficulties. Using LC-QqTOF-MS, we established a system that enabled the quantitation of five AGEs (CML, CEL, MG-H1, CMA and pentosidine) as well as two mature and three immature enzymatic crosslinks. Human bone samples were collected from 149 patients who underwent total knee arthroplasty. Their clinical parameters were collected to investigate parameters that may be predictive of AGE accumulation. All the analytes were quantitated and showed significant linearity with high sensitivity and precision. The results showed that MG-H1 was the most abundant AGE, whereas pentosidine was 1/200–1/20-fold less abundant than the other four AGEs. The AGEs were significantly and strongly correlated with pentosidine, while showing moderate correlation with tfAGEs. Interestingly, multiple linear regression analysis revealed that gender contributed most to the accumulation of all the AGEs, followed by age, tartrate-resistant acid phosphatase-5b and HbA1c. Furthermore, the AGEs were negatively correlated with immature crosslinks. Mass spectrometric quantitation of AGEs and enzymatic crosslinks is crucial to a better understanding of ageing- and disease-related deterioration of bone strength.
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