RAGE-dependent mitochondria pathway: a novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products.
RAGE-dependent mitochondria pathway: a novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products.
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“RAGE 依赖性线粒体途径：水飞蓟宾对抗晚期糖基化终末产物诱导的成骨细胞凋亡的新靶点
DOI：
10.1038/s41419-018-0718-3
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发表时间：
2018-06-04
影响因子：
9
通讯作者：
Huang SB
中科院分区：
文献类型：
--
作者：
Mao YX;Cai WJ;Sun XY;Dai PP;Li XM;Wang Q;Huang XL;He B;Wang PP;Wu G;Ma JF;Huang SB
糖基化终末产物（AGEs）可刺激成骨细胞凋亡，在糖尿病骨质疏松的病理生理过程中起重要作用。线粒体异常与成骨细胞功能障碍密切相关。然而，目前尚不清楚线粒体异常是否参与AGE诱导的成骨细胞凋亡。水飞蓟宾是水飞蓟素的主要黄酮木脂素类化合物，具有很强的抗氧化和抗衰老作用。本研究探讨了AGE诱导成骨细胞凋亡的线粒体机制及水飞蓟宾对成骨细胞凋亡的影响。我们证明，线粒体异常在很大程度上有助于AGE诱导的成骨细胞凋亡，如线粒体氧化应激增强，线粒体膜电位和三磷酸腺苷生产，异常的线粒体形态，线粒体动力学改变的显着减少。这些AGEs诱导的线粒体异常主要由AGEs受体介导。此外，我们发现，水飞蓟宾直接下调表达的RAGE和调制介导的线粒体途径，从而防止AGE诱导的成骨细胞凋亡。本研究不仅为了解AGE诱导成骨细胞凋亡的线粒体机制提供了新的思路，而且为水飞蓟宾在临床上用于预防或治疗糖尿病性骨质疏松症奠定了基础。
Advanced glycation end products (AGEs) can stimulate osteoblast apoptosis and have a critical role in the pathophysiology of diabetic osteoporosis. Mitochondrial abnormalities are closely related to osteoblast dysfunction. However, it remains unclear whether mitochondrial abnormalities are involved in AGE-induced osteoblastic cell apoptosis. Silibinin, a major flavonolignan compound of silimarin, has strong antioxidant and mitochondria-protective properties. In the present study, we explored the possible mitochondrial mechanisms underlying AGE-induced apoptosis of osteoblastic cells and the effect of silibinin on osteoblastic cell apoptosis. We demonstrated that mitochondrial abnormalities largely contributed to AGE-induced apoptosis of osteoblastic cells, as evidenced by enhanced mitochondrial oxidative stress, conspicuous reduction in mitochondrial membrane potential and adenosine triphosphate production, abnormal mitochondrial morphology, and altered mitochondrial dynamics. These AGE-induced mitochondrial abnormalities were mainly mediated by the receptor of AGEs (RAGE). In addition, we found that silibinin directly downregulated the expression of RAGE and modulated RAGE-mediated mitochondrial pathways, thereby preventing AGE-induced apoptosis of osteoblastic cells. This study not only provides a new insight into the mitochondrial mechanisms underlying AGE-induced osteoblastic cell apoptosis, but also lays a foundation for the clinical use of silibinin for the prevention or treatment of diabetic osteoporosis.
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影响因子：
3.7
作者：
Moriishi T;Kawai Y;Komori H;Rokutanda S;Eguchi Y;Tsujimoto Y;Asahina I;Komori T
通讯作者：
Komori T
影响因子：
4.1
作者：
Alikhani, Mani;Alikhani, Zoubin;Graves, Dana T.
通讯作者：
Graves, Dana T.
影响因子：
7.4
作者：
Ng, Li Fang;Gruber, Jan;Halliwell, Barry
通讯作者：
Halliwell, Barry
水飞蓟宾激活 Sirtuin 3 可减轻顺铂诱导的急性肾损伤中的线粒体功能障碍
影响因子：
5.6
作者：
Li Y;Ye Z;Lai W;Rao J;Huang W;Zhang X;Yao Z;Lou T
通讯作者：
Lou T
影响因子：
7.7
作者：
Al-Mashat, HA;Kandru, S;Graves, DT
通讯作者：
Graves, DT