Osteoclasts are multinucleated bone resorbing cells whose differentiation is regulated by several important signaling pathways. Several lines of evidence indicate that dihydroartemisinin (DHA), an anti-malarial drug, inhibits osteoclast differentiation with little cytotoxicity. However, the detailed inhibitory mechanisms of DHA on osteoclastogenesis from native cells remain to be elucidated. In this study, we investigated the effects of DHA on the differentiation of bone marrow-derived macrophages into osteoclasts. DHA inhibited receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclast formation and its bone resorbing activity. Mechanistically, DHA treatment markedly abolished phosphorylation of IκBα, and slightly affected a p38 MAPK dependent pathway. Moreover, DHA treatment induced down-regulation of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), a master regulator for osteoclast differentiation and its target proteins, such as Src and cathepsin K. These results indicate that DHA represses RANKL-induced osteoclastogenesis of bone marrow macrophages through reduced NFATc1 expression and impaired phosphorylation of IκBα.

中文翻译：

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双氢青蒿素通过降低 NFATc1 表达和 IκBα 磷酸化受损来抑制骨髓巨噬细胞的破骨细胞生成。

破骨细胞是多核骨吸收细胞，其分化受几个重要的信号通路调节。多项证据表明，双氢青蒿素 (DHA) 是一种抗疟疾药物，可抑制破骨细胞分化，且几乎没有细胞毒性。然而，DHA 对来自天然细胞的破骨细胞生成的详细抑制机制仍有待阐明。在这项研究中，我们研究了 DHA 对骨髓来源的巨噬细胞向破骨细胞分化的影响。DHA抑制核因子κ-B配体（RANKL）诱导的破骨细胞形成的受体激活剂及其骨吸收活性。从机制上讲，DHA 处理显着消除了 IκBα 的磷酸化，并轻微影响了 p38 MAPK 依赖性途径。而且，