Chen Shuai, Jin Gu, Huang Kang-Mao, Ma Jian-Jun, Wang Qiang, Ma Yan, Tang Xiao-Zhen, Zhou Zhi-Jie, Hu Zhi-Jun, Wang Ji-Ying, Qin An, Fan Shun-Wu
1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Department of Bone and Soft Tissue Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China.
Sci Rep. 2015 Aug 4;5:12853. doi: 10.1038/srep12853.
Osteoclasts play an important role in diseases involving bone loss. In this study, we assessed the effect of a plant-derived natural alkaloid (lycorine, or LY) on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis could be inhibited by LY; this effect was due to inhibition of mitogen-activated protein kinase (MAPK) signalling via MAP kinase kinases (MKKs). The MAPK agonist anisomycin could partially rescue the inhibitory effect of LY. Furthermore, LY also played a protective role in both a murine ovariectomy (OVX)-induced osteoporosis model and a titanium particle-induced osteolysis model. These results confirmed that LY was effective in preventing osteoclast-related diseases in vivo. In conclusion, our results show that LY is effective in suppressing osteoclastogenesis and therefore could be used to treat OVX-induced osteoporosis and wear particle-induced osteolysis.
破骨细胞在涉及骨质流失的疾病中起重要作用。在本研究中,我们评估了一种植物来源的天然生物碱(石蒜碱,或LY)在体外和体内对破骨细胞生成的影响。我们的体外研究表明,核因子κB受体激活剂配体(RANKL)诱导的破骨细胞生成可被LY抑制;这种作用是由于通过丝裂原活化蛋白激酶激酶(MKKs)抑制丝裂原活化蛋白激酶(MAPK)信号传导所致。MAPK激动剂茴香霉素可部分挽救LY的抑制作用。此外,LY在小鼠卵巢切除(OVX)诱导的骨质疏松模型和钛颗粒诱导的骨溶解模型中均发挥了保护作用。这些结果证实LY在体内预防破骨细胞相关疾病方面是有效的。总之,我们的结果表明LY在抑制破骨细胞生成方面是有效的,因此可用于治疗OVX诱导的骨质疏松和磨损颗粒诱导的骨溶解。