Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function

Hye In Lee, Jiae Lee, Donghyun Hwang, Gong Rak Lee, Narae Kim, Minjeong Kwon, Hana Lee, Donglan Piao, Hyun Jin Kim, Nam Young Kim, Han Sung Kim, Eun Kyoung Seo, Dongmin Kang, Woojin Jeong

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9 Citations (Scopus)

Abstract

Excessive osteoclast activity can lead to an imbalance between the synthesis and breakdown of bone, with pathologic consequences that include osteoporosis and periodontitis. Thus, controlling osteoclast differentiation and function has significant therapeutic implications. In this study, we investigated the effects of dehydrocostus lactone (DL) on osteoclast differentiation and activation and elucidated the possible mechanisms underlying these processes. DL suppressed osteoclast differentiation by reducing the expression of the nuclear factor of activated T-cells, cytoplasmic 1. When used to challenge differentiated osteoclasts, DL also effectively inhibited their enlargement and resorption activity, and biochemical approaches revealed that DL attenuates osteoclast activation by inhibiting the migration and lysosome biogenesis and secretion via the down-regulation of integrin β3, PKC-β, and autophagy related 5 expression. Furthermore, DL prevented bone destruction in inflammation- and ovariectomy-induced osteolytic mouse models. These results indicate that DL has therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.—Lee, H. I., Lee, J., Hwang, D., Lee, G.-R., Kim, N., Kwon, M., Lee, H., Piao, D., Kim, H. J., Kim, N. Y., Kim, H. S., Seo, E. K., Kang, D., Jeong, W. Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function. FASEB J. 33, 9685–9694 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)9685-9694
Number of pages10
JournalFASEB Journal
Volume33
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) Grants (2017R1A2B2012435, 2012R1A5A1048236, 2019R1C1C1011198, and 2018R1D1A1A02049371) funded by the Korean Ministry of Science, ICT, and Future Planning (MS1P). The authors declare no conflicts of interest.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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