Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signalregulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway
Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signalregulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway
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DOI：
10.1074/jbc.m115.669499
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发表时间：
2015-11-20
影响因子：
4.8
通讯作者：
Yang, Mao-Wei
中科院分区：
文献类型：
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作者：
Meng, Hong-Zheng;Zhang, Wei-Lin;Yang, Mao-Wei
晚期糖基化终产物（AGEs）和AGEs受体（RAGE）之间的相互作用与糖尿病相关性骨质疏松症的发生和进展有关，但其机制尚不清楚。在本研究中，我们发现age修饰的牛血清白蛋白（AGE-BSA）对hFOB1.19细胞的活力有双相影响；低剂量AGE-BSA刺激细胞增殖，高剂量AGE-BSA刺激细胞凋亡。低剂量AGE-BSA通过同时促进自噬、RAGE生成和Raf/MEK/ERK信号通路激活来促进hEOB1.19细胞的增殖。此外，我们还研究了AGE-BSA对hFOBL19细胞功能的影响，有趣的是，结果表明，低剂量AGE-BSA的短期作用可能通过自噬和RAGE/Raf/MEK/ERK信号通路介导成骨功能的增强和破骨功能的降低。相反，随着治疗时间的延长，观察到相反的效果。总的来说，AGE-BSA对hEOB1.19细胞的体外活性有双相影响，其影响程度由AGE-BSA浓度和处理时间决定。低浓度AGE-BSA通过与RAGE相互作用激活Raf/MEK/ERK信号通路，诱导自噬，调节hFOB1.19细胞的增殖和功能。
The interaction between advanced glycation end products (AGEs) and receptor of AGEs (RAGE) is associated with the development and progression of diabetes-associated osteoporosis, but the mechanisms involved are still poorly understood. In this study, we found that AGE-modified bovine serum albumin (AGE-BSA) induced a biphasic effect on the viability of hFOB1.19 cells; cell proliferation was stimulated after exposure to low dose AGE-BSA, but cell apoptosis was stimulated after exposure to high dose AGE-BSA. The low dose AGE-BSA facilitates proliferation of hEOB1.19 cells by concomitantly promoting autophagy, RAGE production, and the Raf/MEK/ERK signaling pathway activation. Furthermore, we investigated the effects of AGE-BSA on the function of hFOBL19 cells, Interestingly, the results suggest that the short term effects of low dose AGE-BSA increase osteogenic function and decrease osteoclastogenic function, which are likely mediated by autophagy and the RAGE/Raf/MEK/ERK signal pathway. In contrast, with increased treatment time, the opposite effects were observed. Collectively, AGE-BSA had a biphasic effect on the viability of hEOB1.19 cells in vitro, which was determined by the concentration of AGE-BSA and treatment time. A low concentration of AGE-BSA activated the Raf/MEK/ERK signal pathway through the interaction with RAGE, induced autophagy, and regulated the proliferation and function of hFOB1.19 cells.