Advanced oxidation protein products induce pre-osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase-dependent, mitogen-activated protein kinases-mediated intrinsic apoptosis pathway.
Advanced oxidation protein products induce pre-osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase-dependent, mitogen-activated protein kinases-mediated intrinsic apoptosis pathway.
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高级氧化蛋白产品通过烟酰胺腺嘌呤二核苷酸磷酸氧化酶依赖性、丝裂原激活蛋白激酶介导的内在细胞凋亡途径诱导前成骨细胞细胞凋亡
DOI：
10.1111/acel.12764
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发表时间：
2018-08
期刊：
影响因子：
7.8
通讯作者：
Zhong ZM
中科院分区：
文献类型：
--
作者：
Zhu SY;Zhuang JS;Wu Q;Liu ZY;Liao CR;Luo SG;Chen JT;Zhong ZM
成骨细胞凋亡导致年龄相关性骨丢失。晚期氧化蛋白产物（AOPPs）被认为是氧化应激的标志物和细胞凋亡的有效诱导剂。我们已经证明AOPP蓄积与年龄相关的骨丢失相关。然而，AOPPs对成骨细胞凋亡的影响仍不清楚。成骨细胞MC 3 T3-E1暴露于AOPP通过激活烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶导致活性氧（ROS）过度产生。增加的ROS诱导有丝分裂原活化蛋白激酶（MAPK）的磷酸化，其随后通过诱导线粒体功能障碍、内质网应激和Ca 2+过载触发内在凋亡途径，并最终导致凋亡。老年Sprague-道利大鼠的慢性AOPP负荷诱导成骨细胞凋亡和激活NADPH氧化酶信号级联反应，并伴有骨丢失加速和骨微结构恶化。我们的研究表明AOPP通过NADPH氧化酶依赖性、MAPK介导的内源性凋亡途径诱导成骨细胞凋亡。
Osteoblast apoptosis contributes to age‐related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated that AOPP accumulation was correlated with age‐related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3‐E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced phosphorylation of mitogen‐activated protein kinases (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+ overload and eventually leads to apoptosis. Chronic AOPP loading in aged Sprague‐Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase‐dependent, MAPK‐mediated intrinsic apoptosis pathway.
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影响因子：
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