Oxidative stress modulates osteoblastic differentiation of vascular and bone cells
Oxidative stress modulates osteoblastic differentiation of vascular and bone cells
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DOI：
10.1016/s0891-5849(01)00610-4
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发表时间：
2001-08-15
影响因子：
7.4
通讯作者：
Demer, LL
中科院分区：
文献类型：
--
作者：
Mody, N;Parhami, F;Demer, LL
氧化应激可以调节多种病理条件下的细胞功能，包括动脉粥样硬化。动脉粥样硬化斑块的一个特征是钙矿物质沉积，其似乎是由血管成骨细胞（钙化血管细胞（CVC））分化引起的。为了确定氧化应激在调节CVC活性中的作用，我们用过氧化氢（H2 O2）或黄嘌呤/黄嘌呤氧化酶XXO）处理这些细胞，并评估它们对细胞内氧化应激、分化和矿化的影响。这些药物增加细胞内的氧化应激所确定的2，7二氯荧光素荧光，并增强成骨细胞分化的血管细胞，碱性磷酸酶活性和矿化的基础上。相反，H2 O2和XXO导致骨成骨细胞MC 3 T3-E1和骨髓基质细胞M2- 10 B4的分化标志物的抑制，同时增加氧化应激。此外，最低限度的氧化低密度脂蛋白（NM-LDL），以前显示，以提高血管细胞和抑制骨细胞分化，也增加了细胞内的氧化应激在三种细胞类型。XXO和MM-LDL的这些作用被抗氧化剂Trolox和吡咯烷二硫代氨基甲酸酯抵消。这些结果表明，氧化应激调节血管和骨细胞的分化相反，这可以解释平行的建设和钙化的损失，分别在血管钙化和骨质疏松症。(C)2001 Elsevier Science Inc.
Oxidative stress may regulate cellular function in multiple pathological conditions, including atherosclerosis. One feature of the atherosclerotic plaque is calcium mineral deposition, which appears to result from the differentiation of vascular osteoblastic cells, calcifying vascular cells (CVC). To determine the role of oxidative stress in regulating the activity of CVC, we treated these cells with hydrogen peroxide (H2O2) or xanthine/xanthine oxidase XXO) and assessed their effects on intracellular oxidative stress, differentiation, and mineralization. These agents increased intracellular oxidative stress as determined by 2,7 dichlorofluorescein fluorescence, and enhanced osteoblastic differentiation of vascular cells, based on alkaline phosphatase activity and mineralization. In contrast, H2O2 and XXO resulted in inhibition of differentiation markers in bone osteoblastic cells, MC3T3-E1, and marrow stromal cells, M2-10B4, while increasing oxidative stress. In addition, minimally oxidized low-density lipoprotein (NM-LDL), previously shown to enhance vascular cell and inhibit bone cell differentiation, also increased intracellular oxidative stress in the three cell types. These effects of XXO and MM-LDL were counteracted by the antioxidants Trolox and pyrrolidinedithiocarbamate. These results suggest that oxidative stress modulates differentiation of vascular and bone cells oppositely, which may explain the parallel buildup and loss of calcification, seen in vascular calcification and osteoporosis, respectively. (C) 2001 Elsevier Science Inc.