Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells
Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells
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DOI：
10.1152/ajpcell.00361.2007
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发表时间：
2008-04-01
影响因子：
5.5
通讯作者：
Moreau, R.
中科院分区：
文献类型：
--
作者：
Hamel, P.;Abed, E.;Moreau, R.
流行病学研究表明，患有动脉粥样硬化的患者容易患骨质疏松症。氧化低密度脂蛋白（oxLDL）颗粒等致动脉粥样硬化决定因素已被证明既能刺激成骨成骨细胞的增殖，又能促进其凋亡。鉴于这种相反的反应，我们描述了成骨细胞中 oxLDL 诱导的兴奋效应样效应。 oxLDL诱导双相3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)还原活性反应，其中低浓度(10-50μg/ml)增加而高浓度(150μg/ml以上)降低MTT活性。 oxLDL 刺激细胞增殖是 MTT 活性增加的部分原因。未发现线粒体质量发生改变，而低浓度的 oxLDL 会诱导线粒体超极化并增加细胞活性氧 (ROS) 水平。 oxLDL 诱导的 MTT 活性与细胞内 ROS 水平无关。 OxLDL 增加了 NAD(P) H 相关的细胞荧光，而黄素酶抑制剂二亚苯基碘鎓降低了基础和 oxLDL 诱导的 MTT 活性，表明 NAD(P) H 依赖性细胞还原潜力增强。低浓度的oxLDL降低了细胞硫醇含量并增加了金属硫蛋白表达，表明诱导了维持细胞氧化还原状态的补偿机制。这些浓度的 oxLDL 降低了成骨细胞碱性磷酸酶活性和细胞迁移。我们的结果表明，低浓度的oxLDL颗粒会引起刺激样反应，刺激增殖和细胞NAD(P) H依赖性还原电位，而高浓度会导致与细胞死亡相关的MTT活性降低。鉴于低浓度的 oxLDL 对成骨细胞功能的影响，oxLDL 可能会导致骨重塑平衡受损。
Epidemiological studies indicate that patients suffering from atherosclerosis are predisposed to develop osteoporosis. Atherogenic determinants such as oxidized low- density lipoprotein (oxLDL) particles have been shown both to stimulate the proliferation and promote apoptosis of bone- forming osteoblasts. Given such opposite responses, we characterized the oxLDL- induced hormesis- like effects in osteoblasts. Biphasic 3-(4,5- dimethylthiazol- 2- yl)- 2,5- diphenyltetrazolium bromide (MTT) reductive activity responses were induced by oxLDL where low concentrations (10 - 50 mu g/ml) increased and high concentrations (from 150 mu g/ ml) reduced the MTT activity. Cell proliferation stimulation by oxLDL partially accounted for the increased MTT activity. No alteration of mitochondria mass was noticed, whereas low concentrations of oxLDL induced mitochondria hyperpolarization and increased the cellular levels of reactive oxygen species (ROS). The oxLDL- induced MTT activity was not related to intracellular ROS levels. OxLDL increased NAD(P) H- associated cellular fluorescence and flavoenzyme inhibitor diphenyleneiodonium reduced basal and oxLDL- induced MTT activity, suggesting an enhancement of NAD(P) H- dependent cellular reduction potential. Low concentrations of oxLDL reduced cellular thiol content and increased metallothionein expression, suggesting the induction of compensatory mechanisms for the maintenance of cell redox state. These concentrations of oxLDL reduced osteoblast alkaline phosphatase activity and cell migration. Our results indicate that oxLDL particles cause hormesis- like response with the stimulation of both proliferation and cellular NAD(P) H- dependent reduction potential by low concentrations, whereas high concentrations lead to reduction of MTT activity associated with the cell death. Given the effects of low concentrations of oxLDL on osteoblast functions, oxLDL may contribute to the impairment of bone remodeling equilibrium.