Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy
Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy
复制标题
糖皮质激素：通过活性氧和自噬对破骨细胞形成和功能产生剂量相关的影响。
DOI：
10.1016/j.bone.2015.06.014
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发表时间：
2015-10-01
期刊：
影响因子：
4.1
通讯作者：
Luo, Zhuojing
中科院分区：
文献类型：
--
作者：
Shi, Jun;Wang, Long;Luo, Zhuojing
糖皮质激素是否直接促进或干扰破骨细胞的发生仍是一个有争议的话题。在本研究中，我们确定了糖皮质激素在体内和体外对成骨细胞的促进作用，并探讨了其作用机制。随着糖皮质激素剂量的增加，破骨细胞生成在0.1mM时被刺激，在1mM时达到峰值，在10mU时相应下降。在破骨细胞形成中起关键作用的活性氧(ROS)随着糖皮质激素对破骨细胞形成和功能的剂量依赖性作用而持续上调。ROS清除剂N-乙酰半胱氨酸(NAC)消除了糖皮质激素对自噬和破骨细胞生成的影响。此外，自噬抑制剂3-甲基腺嘌呤(3-MA)阻断了糖皮质激素对破骨细胞的刺激。这些结果提示，在糖皮质激素作用下，ROS和自噬作为ROS的下游因子，在破骨细胞的形成和功能中起着至关重要的作用。3-MA不能增加ROS的积聚，自噬对糖皮质激素诱导的ROS无影响。我们的研究表明，糖皮质激素通过ROS和自噬对破骨细胞的形成和功能具有剂量依赖性的积极作用。这些结果支持ROS和自噬作为糖皮质激素相关骨丢失疾病的治疗靶点，如糖皮质激素诱导的骨质疏松。(C)2015 Elsevier Inc.保留所有权利。
Whether glucocorticoids directly enhance or interrupt osteoclastogenesis is still a controversial subject. In this study, we ascertained the dose-dependent positive effects of glucocorticoids on osteodastogenesis in vivo and in vitro as well as investigated the mechanism in vitro. As the dose of glucocorticoids increased, osteoclastogenesis was stimulated at 0.1 mu M, a peak was achieved at 1 mu M and a corresponding decrease occurred at 10 mu M. Reactive oxygen species (ROS), which play a crucial role in osteoclastogenesis, and autophagy flux activity, a cellular recycling process, were consistently up-regulated along with the dose-dependent effects of the glucocorticoids on osteoclast formation and function. N-acetyl-cysteine (NAC), a ROS scavenger, abrogated the effects of the glucocorticoids on autophagy and osteoclastogenesis. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, interrupted osteoclastogenesis stimulation by the glucocorticoids. These results implied that with glucocorticoid administration, ROS and autophagy, as a downstream factor of ROS, played vital roles in osteoclast formation and function. 3-MA administration did not enhance ROS accumulation, so that autophagy had no effect on ROS induced by glucocorticoids. Our investigation demonstrated that glucocorticoids had dose-dependent positive effects on osteoclast formation and function via ROS and autophagy. These results provide support for ROS and autophagy as therapeutic targets in glucocorticoid-related bone loss diseases such as glucocorticoid-induced osteoporosis. (C) 2015 Elsevier Inc. All rights reserved.