Cistanche deserticola polysaccharide attenuates osteoclastogenesis and bone resorption via inhibiting RANKL signaling and reactive oxygen species production
Cistanche deserticola polysaccharide attenuates osteoclastogenesis and bone resorption via inhibiting RANKL signaling and reactive oxygen species production
复制标题
肉苁蓉多糖通过抑制 RANKL 信号传导和活性氧产生来减弱破骨细胞生成和骨吸收
DOI：
10.1002/jcp.26882
复制
发表时间：
2018-12-01
影响因子：
5.6
通讯作者：
Xu, Jiake
中科院分区：
文献类型：
--
作者：
Song, Dezhi;Cao, Zhen;Xu, Jiake
骨质疏松症是一种以骨量减少和骨微结构恶化为特征的代谢性疾病。破骨细胞是降解骨基质的主要效应细胞，其异常功能导致骨质疏松的发生。细胞代谢过程中ROS的积累促进了破骨细胞的增殖和分化，在骨质疏松中起着重要作用。肉桂多糖(CDP)具有抗肿瘤、抗炎、抗氧化等活性。然而，CDP对破骨细胞的影响尚不清楚。本研究采用抗酒石酸酸性磷酸酶染色、免疫荧光、逆转录-聚合酶链式反应和蛋白质印迹分析等方法，证明CDP可抑制破骨细胞的形成和羟基磷灰石的吸收。此外，顺铂还可抑制破骨细胞标志物基因CTSK、MMP9和Acp5的表达，而对核因子受体激活剂κB(RANK)的表达无影响。机制分析表明，CDP增加抗氧化酶的表达，以减少RANKL介导的破骨细胞ROS的产生，并抑制激活的T细胞的核因子和丝裂原激活的蛋白激酶的激活。这些结果提示CDP可能是治疗破骨细胞过度活动引起的骨质疏松的候选药物。
Osteoporosis is a metabolic disease characterized by osteopenia and bone microstructural deterioration. Osteoclasts are the primary effector cells that degrade bone matrix and their abnormal function leads to the development of osteoporosis. Reactive oxygen species (ROS) accumulation during cellular metabolism promotes osteoclast proliferation and differentiation, therefore, playing an important role in osteoporosis. Cistanche deserticola polysaccharide (CDP) possesses antitumor, anti‐inflammatory, and antioxidant activity. However, the impact of CDP on osteoclasts is unclear. In this study, tartrate‐resistant acid phosphatase staining, immunofluorescence, reverse transcription‐polymerase chain reaction, and western blot analysis were utilized to demonstrate that CDP inhibited osteoclastogenesis and hydroxyapatite resorption. In addition, CDP also inhibited the expression of osteoclast maker genes including Ctsk, Mmp9, and Acp5 and had no effect on receptor activator of nuclear factor κB (RANK) expression. Mechanistic analyses revealed that CDP increases the expression of antioxidant enzymes to attenuate RANKL‐mediated ROS production in osteoclasts and inhibits nuclear factor of activated T cells and mitogen‐activated protein kinase activation. These results suggest that CDP may represent a candidate drug for the treatment of osteoporosis caused by excessive osteoclast activity.