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氧化型低密度脂蛋白(LDL)对成骨细胞活力的影响。

Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells.

作者信息

Brodeur Mathieu R, Brissette Louise, Falstrault Louise, Ouellet Pascale, Moreau Robert

机构信息

Département des Sciences Biologiques, Université du Québec à Montréal, CP 8888, succ Centre-Ville, Montreal (Quebec), Canada H3C 3P8.

出版信息

Free Radic Biol Med. 2008 Feb 15;44(4):506-17. doi: 10.1016/j.freeradbiomed.2007.08.030. Epub 2007 Sep 15.

Abstract

Cardiovascular diseases have recently been noted as potential risk factors for osteoporosis development. Although it is poorly understood how these two pathologies are related, it is a known fact that oxidized low-density lipoproteins (OxLDL) constitute potential determinants for both of them. The current study investigated the metabolism of OxLDL by osteoblasts and its effect on osteoblastic viability. The results obtained show that OxLDL are internalized but not degraded by osteoblasts while they can selectively transfer their CE to these cells. It is also demonstrated that OxLDL induce proliferation at low concentrations but cell death at high concentrations. This reduction of osteoblast viability was associated with lysosomal membrane damage caused by OxLDL as demonstrated by acridine orange relocalization. Accordingly, chloroquine, an inhibitor of lysosomal activity, accentuated cell death induced by OxLDL. Finally, we demonstrate that osteoblasts have the capacity to oxidize LDL and thereby potentially increase the local concentration of OxLDL. Overall, the current study confirms the potential role of OxLDL in the development of osteoporosis given its influence on osteoblastic viability.

摘要

心血管疾病最近被认为是骨质疏松症发展的潜在风险因素。尽管人们对这两种病症之间的关联了解甚少,但已知氧化型低密度脂蛋白(OxLDL)是这两种病症的潜在决定因素。当前的研究调查了成骨细胞对OxLDL的代谢及其对成骨细胞活力的影响。所获得的结果表明,OxLDL被成骨细胞内化但未被降解,同时它们可以选择性地将其胆固醇酯转移至这些细胞。研究还表明,OxLDL在低浓度时诱导增殖,但在高浓度时导致细胞死亡。吖啶橙重新定位显示,成骨细胞活力的这种降低与OxLDL引起的溶酶体膜损伤有关。因此,溶酶体活性抑制剂氯喹加剧了OxLDL诱导的细胞死亡。最后,我们证明成骨细胞具有氧化低密度脂蛋白的能力,从而可能增加局部OxLDL的浓度。总体而言,鉴于OxLDL对成骨细胞活力的影响,当前的研究证实了OxLDL在骨质疏松症发展中的潜在作用。

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