Age-related accumulation of advanced oxidation protein products promotes osteoclastogenesis through disruption of redox homeostasis.
Age-related accumulation of advanced oxidation protein products promotes osteoclastogenesis through disruption of redox homeostasis.
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与年龄相关的高级氧化蛋白产物的积累通过破坏氧化还原稳态来促进破骨细胞生成
DOI：
10.1038/s41419-021-04441-w
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发表时间：
2021-12-14
影响因子：
9
通讯作者：
Zhong Z
中科院分区：
文献类型：
--
作者：
Zhuang J;Chen X;Cai G;Wu D;Tu C;Zhu S;Huang Y;Xu P;Zhong Z
破骨细胞生成增强是年龄相关性骨质流失的主要原因之一。衰老伴随着高级氧化蛋白产物（AOPPs）的积累。然而，AOPPs的积累是否与衰老相关的破骨细胞发生有关尚不清楚。在这里，我们发现AOPPs的积累与老年小鼠破骨细胞生成增强和骨微观结构恶化有关。在体外，AOPPs通过与原代骨髓单核细胞中的核因子κ B受体激活因子（RANK）和晚期糖基化终产物受体（RAGE）相互作用，直接诱导破骨细胞发生。AOPPs与RANK和RAGE结合可激活烟酰胺腺嘌呤二核苷酸磷酸（nictinamide adenine dinucleotide phosphate， NADPH）氧化酶，触发活性氧的产生，进而诱导丝裂原活化蛋白激酶和c-fos磷酸化，活化T细胞c1核因子上调，最终诱导骨髓单核细胞分化为成熟的破骨细胞。慢性暴露于AOPPs可促进小鼠破骨细胞生成和骨质流失，而NADPH氧化酶抑制剂罗布麻素可减轻这一作用。骨膜下区局部注射AOPPs可诱导给药部位骨吸收，其作用与RANK配体相似。综上所述，这些结果表明AOPPs可能是破骨细胞发生的一种新的调节剂，AOPPs的积累可能在年龄相关性骨质流失的发展中发挥重要作用。
Enhanced osteoclastogenesis is one of the major causes of age-related bone loss. Aging is accompanied by accumulation of advanced oxidation protein products (AOPPs). However, whether AOPPs accumulation contributing to the osteoclastogenesis with aging remains unclear. Here, we showed that AOPPs accumulation was associated with the enhanced osteoclastogenesis and deterioration of bone microstructure in aged mice. In vitro, AOPPs directly induced osteoclastogenesis by interaction with receptor activator of nuclear factor κ B (RANK) and the receptor for advanced glycation end products (RAGE) in the primary bone marrow monocytes. Bindings of AOPPs to RANK and RAGE were able to activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, trigger generation of reactive oxygen species, then induce phosphorylation of mitogen-activated protein kinases and c-fos, upregulation of the nuclear factor of activated T cell c1, eventually induce bone marrow monocytes to differentiate into mature osteoclasts. Chronic exposure to AOPPs enhanced osteoclastogenesis and bone loss in mice, which could be alleviated by NADPH oxidase inhibitor apocynin. Local injection of AOPPs into subperiosteal area induced bone resorption at the site of administration, which was similar to the effect of RANK ligand. Together, these results suggested that AOPPs could serve as a novel regulator of osteoclastogenesis and AOPPs accumulation might play an important role in the development of age-related bone loss.
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影响因子：
7.8
作者：
Davis HM;Pacheco-Costa R;Atkinson EG;Brun LR;Gortazar AR;Harris J;Hiasa M;Bolarinwa SA;Yoneda T;Ivan M;Bruzzaniti A;Bellido T;Plotkin LI
通讯作者：
Plotkin LI
影响因子：
10.5
作者：
Dougall, WC;Glaccum, M;Schuh, J
通讯作者：
Schuh, J
影响因子：
5.6
作者：
Lee K;Seo I;Choi MH;Jeong D
通讯作者：
Jeong D
影响因子：
4.1
作者：
Hemingway, F.;Taylor, R.;Athanasou, N. A.
通讯作者：
Athanasou, N. A.
影响因子：
--
作者：
Edwards, J. R.;Sun, S. G.;Sabokbar, A.
通讯作者：
Sabokbar, A.