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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 218 - 222 (5page)
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초록· 키워드
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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.
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참고문헌 (29)
참고문헌 신청
Manolagas SC / 2000 / Birth and death of bone cells : basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis / Endocr Rev 21:115~137
Rodan GA / 2000 / Therapeutic approaches to bone diseases / Science 289:1508~1514
Ross FP / 2005 / alphavbeta3 and macrophage colony-stimulating factor : partners in osteoclast biology / Immunol Rev 208:88~105
Theill LE / 2002 / RANK-L and RANK : T cells, bone loss, and mammalian evolution / Annu Rev Immunol 20:795~823
Asagiri M / 2007 / The molecular understanding of osteoclast differentiation / Bone 40:251~264
Rodan GA / 2000 / Therapeutic approaches to bone diseases / Science 289:1508~1514
Ross FP / 2005 / alphavbeta3 and macrophage colony-stimulating factor : partners in osteoclast biology / Immunol Rev 208:88~105
Theill LE / 2002 / RANK-L and RANK : T cells, bone loss, and mammalian evolution / Annu Rev Immunol 20:795~823
Asagiri M / 2007 / The molecular understanding of osteoclast differentiation / Bone 40:251~264
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