Cumambrin A prevents OVX-induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways

Lin Zhou, Qian Liu, Guoju Hong, Fangming Song, Jinmin Zhao, Jinbo Yuan, Jun Xu, Ren Xiang Tan, Jennifer Tickner, Qiong Gu, Jiake Xu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6726-6735
Number of pages10
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

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Osteoclasts
Bone Resorption
Osteogenesis
Osteoporosis
Bone
Calcitonin Receptors
Chrysanthemum
Cathepsin K
NFATC Transcription Factors
Bone and Bones
Sesquiterpenes
Therapeutic Uses
Lactones
Music
Adenosine Triphosphatases
Estrogens
Phosphorylation
Ligands
Genes
Therapeutics

Cite this

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title = "Cumambrin A prevents OVX-induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways",
abstract = "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.",
keywords = "ERK, NF-κB, NFATc1, osteolysis",
author = "Lin Zhou and Qian Liu and Guoju Hong and Fangming Song and Jinmin Zhao and Jinbo Yuan and Jun Xu and Tan, {Ren Xiang} and Jennifer Tickner and Qiong Gu and Jiake Xu",
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Cumambrin A prevents OVX-induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways. / Zhou, Lin; Liu, Qian; Hong, Guoju; Song, Fangming; Zhao, Jinmin; Yuan, Jinbo; Xu, Jun; Tan, Ren Xiang; Tickner, Jennifer; Gu, Qiong; Xu, Jiake.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 6, 01.06.2019, p. 6726-6735.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cumambrin A prevents OVX-induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways

AU - Zhou, Lin

AU - Liu, Qian

AU - Hong, Guoju

AU - Song, Fangming

AU - Zhao, Jinmin

AU - Yuan, Jinbo

AU - Xu, Jun

AU - Tan, Ren Xiang

AU - Tickner, Jennifer

AU - Gu, Qiong

AU - Xu, Jiake

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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