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Cumambrin A prevents OVX‐induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways
Author(s) -
Zhou Lin,
Liu Qian,
Hong Guoju,
Song Fangming,
Zhao Jinmin,
Yuan Jinbo,
Xu Jun,
Tan Ren Xiang,
Tickner Jennifer,
Gu Qiong,
Xu Jiake
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.201800883rrr
Subject(s) - rankl , bone resorption , osteoporosis , chemistry , resorption , signal transduction , endocrinology , medicine , receptor , biochemistry , activator (genetics)
Being the principal cells responsible for bone resorption and pathologic bone loss, osteoclasts have become the main target for antiresorptive treatment. Cumambrin A is a natural compound isolated from Chrysanthemum indicum L. and belongs to a member of the sesquiterpene lactone family. To date, the therapeutic effect of cumambrin A on osteoporosis and its mechanisms of action are not known. In this study, we found that cumambrin A can significantly inhibit osteoclast formation and bone resorption through the suppression of receptor activator of NF‐κB ligand (RANKL)–induced NF‐κB and nuclear factor of activated T‐cell activity and ERK phosphorylation. Furthermore, cumambrin A inhibits the expression of osteoclast marker genes including cathepsin K, calcitonin receptor, and V‐ATPase d2. Using an in vivo ovariectomized mouse model, we showed that cumambrin A protects against estrogen withdrawal–induced bone loss. Collectively, our results reveal that cumambrin A can suppress osteoclast formation, bone resorption, and RANKL‐induced signaling pathways, suggesting that cumambrin A is a potential therapeutic agent for the treatment of osteoporosis.—Zhou, L., Liu, Q., Hong, G., Song, F., Zhao, J., Yuan, J., Xu, J., Tan, R. X., Tickner, J., Gu, Q., Xu, J. Cumambrin A prevents OVX‐induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways. FASEB J. 33, 6726–6735 (2019). www.fasebj.org