组织蛋白酶K
破骨细胞
蒿甲醚
骨吸收
兰克尔
组织蛋白酶
MAPK/ERK通路
化学
癌症研究
细胞生物学
药理学
信号转导
内科学
医学
免疫学
生物
体外
生物化学
受体
青蒿素
激活剂(遗传学)
酶
疟疾
恶性疟原虫
作者
Haobo Wu,Bin Hu,Xiaopeng Zhou,Chenhe Zhou,Jiahong Meng,Yute Yang,Xiang Zhao,Zhongli Shi,Shigui Yan
标识
DOI:10.1038/s41419-018-0540-y
摘要
Osteolysis is an osteolytic lesion featured by enhanced osteoclast formation and potent bone erosion. Lacking of effective regimen for treatment of the pathological process highlights the importance of identifying agents that can suppress the differentiation and function of osteoclast. Artemether is a natural compound derived from Artemisia annua L. and it is popularized for the treatment of malaria. In present study, we demonstrated that artemether could suppress RANKL-induced osteoclastogenesis and expression of osteoclast marker genes such as tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T-cell cytoplasmic 1, and dendritic cell-specific transmembrane protein. It inhibited the osteoclastic bone resorption in a dose-dependent manner in vitro. Furthermore, artemether attenuated RANKL-induced MAPKs (ERK, JNK, p-38) activity. In addition, we have showed that artemether was able to mitigate bone erosion in a murine model of LPS-induced inflammatory bone loss. Taken together, these findings suggest that artemether reduces inflammatory bone loss via inhibition of MAPKs activation during osteoclast differentiation, and it might be a potential candidate for the treatment of osteoclast-related disorders.
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