Dihydroartemisinin represses osteoclastogenesis of bone marrow macrophages through reduced NFATc1 expression and impaired phosphorylation of IκBα

Shunsuke Komaki, Eiko Sakai, Yutaka Fukuma, Kazuhisa Nishishita, Kuniaki Okamoto, Takayuki Tsukuba

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalBiomedical Research (Japan)
Volume39
Issue number4
DOIs
Publication statusPublished - Jan 1 2018
Externally publishedYes

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dihydroartemisinin
NFATC Transcription Factors
Phosphorylation
Macrophages
Osteogenesis
Bone
Osteoclasts
Bone Marrow
Cathepsin K
Antimalarials
p38 Mitogen-Activated Protein Kinases
Cytotoxicity
Cytoplasmic and Nuclear Receptors
Cell Differentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dihydroartemisinin represses osteoclastogenesis of bone marrow macrophages through reduced NFATc1 expression and impaired phosphorylation of IκBα. / Komaki, Shunsuke; Sakai, Eiko; Fukuma, Yutaka; Nishishita, Kazuhisa; Okamoto, Kuniaki; Tsukuba, Takayuki.

In: Biomedical Research (Japan), Vol. 39, No. 4, 01.01.2018, p. 169-177.

Research output: Contribution to journalArticle

Komaki, Shunsuke ; Sakai, Eiko ; Fukuma, Yutaka ; Nishishita, Kazuhisa ; Okamoto, Kuniaki ; Tsukuba, Takayuki. / Dihydroartemisinin represses osteoclastogenesis of bone marrow macrophages through reduced NFATc1 expression and impaired phosphorylation of IκBα. In: Biomedical Research (Japan). 2018 ; Vol. 39, No. 4. pp. 169-177.
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