Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo.
Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo.
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DOI：
10.1016/j.bbrc.2015.09.093
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发表时间：
2015-10
影响因子：
3.1
通讯作者：
Shuo Yang;Xianan Li;Liang Cheng;Hongwei Wu;Can Zhang;Kanghua Li
中科院分区：
文献类型：
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作者：
Shuo Yang;Xianan Li;Liang Cheng;Hongwei Wu;Can Zhang;Kanghua Li
Tenuigenin是tenuifolia根的主要活性成分，已被用于治疗失眠，痴呆和神经症患者。在本研究中，我们旨在探讨黄芩苷对破骨细胞形成的影响并阐明其可能的机制。我们发现，黄芪黄素可以抑制核因子-κB配体受体激活因子（RANKL）诱导的破骨细胞分化和骨吸收，但没有细胞毒性，进一步通过降低破骨细胞特异性基因如TRAP、c-Src、ATP6v0d2等的表达来证明这一点。此外，由于IkBa的降解/再生延迟和p65核易位的抑制，tenuigenin的抑制作用与NF-κB活性受损有关。与他们的体外实验结果一致，显微ct扫描和分析数据显示，在动物模型中，tenuigenin抑制rankl诱导的骨质流失。综上所述，我们的数据表明，teuigenin在体外和体内抑制破骨细胞的形成和骨吸收，并为破骨细胞相关疾病（如骨质疏松症和癌症诱导的骨破坏）提供了潜在的治疗选择。
Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with thein vitroresults, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption bothin vitroandin vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction.