Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice
Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice
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Diosmetin 抑制破骨细胞的形成和分化，并防止 LPS 诱导的小鼠骨质溶解。
DOI：
10.1002/jcp.27887
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Xu, Jiake
中科院分区：
文献类型：
--
作者：
Shao, Siyuan;Fu, Fangsheng;Xu, Jiake
溶骨性骨病与破骨细胞的过度活化和骨吸收增强密切相关。它已成为全球骨科实践中的一个主要健康问题。破骨细胞的抑制被认为是溶骨性疾病的主要治疗方法。Diosmetin（DIO）是一种天然黄酮类化合物，具有抗氧化、抗感染、抗休克等作用。DIO对破骨细胞分化的影响知之甚少。在本研究项目中，我们发现DIO可以以剂量依赖性方式抑制核因子κ B配体受体激活剂（RANKL）诱导的破骨细胞形成。破骨细胞分化标记基因、组织蛋白酶K、活化T细胞核因子1（NFATc 1）、Acp 5、Ctr、Atp 6v 0 d2和Mmp 9的表达也通过DIO处理而降低。此外，DIO还能抑制肌动蛋白环的形成和骨吸收能力。Western blotting结果显示，DIO可抑制RANKL诱导的丝裂原活化蛋白激酶信号通路的磷酸化，同时下调NFATc 1和c-Fos的表达。我们还发现DIO可以减少RANKL诱导的活性氧（ROS）的积累。在体内，研究表明，DIO可以显着减少LPS诱导的小鼠骨质溶解。总之，我们的研究表明，DIO可以抑制破骨细胞的形成和激活，并可能作为一个潜在的治疗药物溶骨性骨病。
Osteolytic bone diseases are closely linked to the over-activation of osteoclasts and enhancement of bone resorption. It has become a major health issue in orthopedic practice worldwide. Inhibition of osteoclasts is proposed to be the main treatment for osteolytic disorders. Diosmetin (DIO) is a natural flavonoid with properties of antioxidant, anti-infection, and antishock. The effect of DIO on osteoclast differentiation is poorly understood. In this study project, we found that DIO could inhibit osteoclastic formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in a dose-dependent manner. The expression of the osteoclast differentiation marker genes, cathepsin K, nuclear factor of activated T-cells 1 (NFATc1), Acp5, Ctr, Atp6v0d2, and Mmp9 were also decreased by the treatment of DIO. In addition, DIO attenuated the formation of actin ring and the ability of bone resorption. Further, the western blotting showed that DIO inhibits the phosphorylation of the mitogen-activated protein kinases signaling pathway induced by RANKL, accompanied by the downregulation of NFATc1 and c-Fos expression. We also found that DIO could reduce the accumulation of reactive oxygen species (ROS) induced by RANKL. In vivo, the study revealed that DIO can significantly reduce LPS-induced osteolysis in mice. Collectively, our study shows that DIO can inhibit osteoclast formation and activation, and could serve as a potential therapeutic drug for osteolytic bone diseases.