Oxidized Low-Density Lipoprotein Promotes Osteoblastic Differentiation of Valvular Interstitial Cells through RAGE/MAPK
Oxidized Low-Density Lipoprotein Promotes Osteoblastic Differentiation of Valvular Interstitial Cells through RAGE/MAPK
复制标题
氧化低密度脂蛋白通过RAGE/MAPK促进瓣膜间质细胞成骨分化
DOI：
10.1159/000369126
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发表时间：
2015-01-01
期刊：
影响因子：
1.9
通讯作者：
Liu, Yi
中科院分区：
文献类型：
--
作者：
Li, Fei;Zhao, Zhihong;Liu, Yi
目的：我们以前已经表明，氧化低密度脂蛋白（oxLDL）促进成骨分化的瓣膜间质细胞（VIC）诱导内质网（ER）的压力。我们还证实了晚期糖基化终末产物受体（AGEs）激活和信号传导在主动脉瓣（AV）钙化的发生和进展中的有害作用。在这里，我们测试的假设，oxLDL可能会诱导成骨细胞分化的VICs通过骨形成。方法：培养猪主动脉VIC用于体外模型。将VIC与oxLDL一起孵育用于分析，有和没有oxLDL siRNA。结果如下：我们发现，oxLDL显着增加的表达，诱导高水平的促炎细胞因子的产生，并促进成骨细胞分化和钙化的VIC。oxLDL还诱导p38丝裂原活化蛋白激酶（MAPK）和c-Jun N-末端激酶（JNK）MAPK磷酸化。然而，这些作用被发现被siRNA沉默显著抑制。结论：我们的数据提供了证据表明，cytokine介导oxLDL诱导的p38和JNK MAPK的激活和VIC的成骨分化。
Objectives: We have previously shown that oxidized low-density lipoprotein (oxLDL) promotes the osteogenic differentiation of valvular interstitial cells (VICs) by inducing endoplasmic reticulum (ER) stress. We also demonstrated the detrimental role of the receptor for advanced glycation end products (RAGE) activation and signaling in the development and progression of aortic valve (AV) calcification. Here, we test the hypothesis that oxLDL may induce the osteoblastic differentiation of VICs via RAGE. Methods: Cultured porcine aortic VICs were used in an in vitro model. The VICs were incubated with oxLDL for analysis, with and without RAGE siRNA. Results: We found that oxLDL markedly increased the expression of RAGE, induced high levels of proinflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs. oxLDL also induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) MAPK. However, these effects were found to be markedly suppressed by siRNA silencing of RAGE. Conclusions: Our data provide evidence that RAGE mediates oxLDL-induced activation of p38 and JNK MAPK and the osteogenic differentiation of VICs.