Dehydrocostus lactone inhibits NFATc1 via regulation of IKK, JNK, and Nrf2, thereby attenuating osteoclastogenesis

Hye In Lee, Gong Rak Lee, Jiae Lee, Narae Kim, Minjeong Kwon, Hyun Jin Kim, Nam Young Kim, Jin Ha Park, Woojin Jeong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-B (NF-B), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated IB phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-B target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signalregulated kinase. The reporter assay revealed that DL inhibits NF-B and AP-1 activation. In addition, DL reduced reactive oxygen species either by scavenging them or by activating Nrf2. The DL inhibition of NFATc1 expression and osteoclast differentiation was less effective in Nrf2-deficient cells. Collectively, these results suggest that DL regulates NFATc1 by inhibiting NF-B and AP-1 via down-regulation of IB kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation.

Original languageEnglish
Pages (from-to)218-222
Number of pages5
JournalBMB Reports
Volume53
Issue number4
DOIs
StatePublished - 2020

Keywords

  • AP-1
  • NF-κB
  • NFATc1
  • Nrf2
  • Osteoclast
  • ROS

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