薯蓣皂苷通过下调 Akt 信号级联抑制破骨细胞分化和骨吸收。
Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades.
机构信息
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
出版信息
Biochem Biophys Res Commun. 2014 Jan 10;443(2):658-65. doi: 10.1016/j.bbrc.2013.12.029. Epub 2013 Dec 11.
Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.
骨吸收是破骨细胞（OCs）的独特功能，对骨稳态和包括骨质疏松症、类风湿关节炎和肿瘤骨转移在内的病理性骨疾病都至关重要。因此，寻找可能抑制破骨细胞形成和/或功能的天然化合物，对于治疗与破骨细胞相关的疾病具有广阔的前景。在这项研究中，我们首次证明薯蓣皂苷元能够以剂量依赖的方式抑制 RANKL 介导的体外破骨细胞分化和骨吸收。薯蓣皂苷元的抑制作用得到了破骨细胞特异性标志物表达降低的支持。进一步的分子分析表明，薯蓣皂苷元抑制了 AKT 的磷酸化，从而损害了 RANKL 诱导的核因子-κB（NF-κB）信号通路，并抑制了 NFATc1 的转录活性。此外，体内研究进一步验证了薯蓣皂苷元在溶骨性动物模型中的骨保护活性。综上所述，薯蓣皂苷元通过 Akt 信号级联抑制 RANKL 诱导的破骨细胞形成和功能。因此，薯蓣皂苷元是一种有潜力的治疗与破骨细胞相关疾病的天然药物。
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