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Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function
Author(s) -
Lee Hye In,
Lee Jiae,
Hwang Donghyun,
Lee GongRak,
Kim Narae,
Kwon Minjeong,
Lee Hana,
Piao Donglan,
Kim Hyun Jin,
Kim Nam Young,
Kim Han Sung,
Seo Eun Kyoung,
Kang Dongmin,
Jeong Woojin
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900862r
Subject(s) - osteoclast , chemistry , microbiology and biotechnology , lysosome , bone resorption , autophagy , cancer research , endocrinology , biochemistry , biology , apoptosis , receptor , enzyme
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 β 3 , 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