Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction.
Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction.
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DOI：
10.1016/j.bbrc.2015.11.022
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发表时间：
2015-12-25
影响因子：
3.1
通讯作者：
Yan SS
中科院分区：
文献类型：
--
作者：
Gan X;Huang S;Yu Q;Yu H;Yan SS
氧化应激诱导的成骨细胞功能障碍在骨质疏松症的病理生理学中起着关键作用。然而，其基本机制仍不清楚。线粒体动力学的不平衡与氧化应激密切相关。在这里，我们揭示了动态相关蛋白1（Drp1），线粒体分裂的主要调节器，在氧化应激诱导的成骨细胞损伤模型中的未探索的作用。我们证明，磷酸化水平和表达的Drp1显着增加氧化应激。阻断Drp1，通过药物抑制剂或基因敲低，显着防止过氧化氢诱导的成骨细胞功能障碍，如所示的细胞活力增加，改善细胞碱性磷酸酶（ALP）的活性和矿化和恢复线粒体功能。通过增加线粒体功能和抑制活性氧（ROS）的产生，证明了阻断Drp1在H2O2诱导的成骨细胞功能障碍中的保护作用。这些发现为Drp1依赖性线粒体途径在骨质疏松症病理学中的作用提供了新的见解，表明Drp1途径可能是开发预防和治疗骨质疏松症的新治疗方法的目标。
Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H2O2-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H2O2-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis.