HDL3 Reduces the Association and Modulates the Metabolism of Oxidized LDL by Osteoblastic Cells: A Protection Against Cell Death
HDL3 Reduces the Association and Modulates the Metabolism of Oxidized LDL by Osteoblastic Cells: A Protection Against Cell Death
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DOI：
10.1002/jcb.21938
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发表时间：
2008-12-15
影响因子：
4
通讯作者：
Moreau, Robert
中科院分区：
文献类型：
--
作者：
Brodeur, Mathieu R.;Brissette, Louise;Moreau, Robert
已知氧化低密度脂蛋白（OxLDL）促进动脉粥样硬化，但直到最近，OxLDL才与骨形成成骨细胞的功能改变和骨质疏松症相关。虽然高密度脂蛋白（HDL）被认为具有抗动脉粥样硬化作用，但关于其预防骨质疏松症的能力的信息较少。因此，我们研究了HDL 3阻止OxLDL诱导的人成骨细胞死亡的能力。同时暴露于HDL 3和OxLDL可消除MTT活性检测的细胞活力降低和Annexin V染色检测的细胞凋亡诱导，表明HDL 3可阻止OxLDL诱导的成骨细胞凋亡。这种保护与OxLDL与成骨细胞结合的HDL 3置换相关，表明OxLDL结合和/或内化是其细胞毒性作用所必需的。我们还发现，暴露的成骨细胞与氧化低密度脂蛋白孵育前的高密度脂蛋白3减少细胞死亡，并保持溶酶体的完整性。这种保护与SR-BI表达的增加相关，这是一种OxLDL代谢的修饰，具有较少的OxLDL整体摄取和更大的选择性摄取OxLDL中的胆固醇。这些结果有力地表明，与动脉粥样硬化一样，HDL可能对骨代谢产生有益的作用。J.细胞。105：1374-1385，2008. (C)2008 Wiley-Liss，Inc.
Oxidized low density lipoproteins (OxLDL) are known to promote atherosclerosis, but it is only recently that OxLDL have been associated with alterations of the functions of bone-forming osteoblasts and osteoporosis. Although high density lipoproteins (HDL) are recognized for their anti-atherogenic action, there is less information about their ability to protect against osteoporosis. Therefore, we investigated the capacity of HDL3 to prevent the cell death induced by OxLDL in human osteoblastic cells. Simultaneous exposure of the cells to HDL3 and OxLDL abolished the reduction of cell viability monitored by MTT activity measurement and the induction of apoptosis determined by annexin V staining indicating that HDL3 prevent the apoptosis of osteoblasts induced by OxLDL,. This protection correlated with the displacement by HDL3 of OxLDL association to osteoblasts, signifying that OxLDL binding and/or internalization are/is necessary for their cytotoxic effects. We also found that exposition of osteoblastic cells to HDL3 prior to incubation with OxLDL reduced cell death and preserved the lysosomal integrity. This protection was correlated with an increase of SR-BI expression, a modification of OxLDL metabolism with less global uptake of OxLDL and greater selective uptake or cholesterol from OxLDL. These results strongly suggest that, as for atherosclerosis, HDL may exert beneficial actions on bone metabolism. J. Cell. Biochem. 105: 1374-1385, 2008. (C) 2008 Wiley-Liss, Inc.