Dehydrocostus lactone inhibits NFATc1 via regulation of IKK, JNK, and Nrf2, thereby attenuating osteoclastogenesis
- 주제(키워드) AP-1 , NFATc1 , NF-kappa B , Nrf2 , Osteoclast , ROS
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Jeong, Woojin] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published, gold
- 발행기관 KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168767
- 본문언어 영어
- Published As https://dx.doi.org/10.5483/BMBRep.2020.53.4.220
- PubMed https://pubmed.ncbi.nlm.nih.gov/31964469
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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-kappa B (NF-kappa B), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated I kappa B alpha phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-kappa B target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signal-regulated kinase. The reporter assay revealed that DL inhibits NF-kappa 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-kappa B and AP-1 via down-regulation of I kappa B kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation.
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