Dehydrocostus lactone (DHC) suppresses estrogen deficiency-induced osteoporosis

Zhaoning Li, Guixin Yuan, Xixi Lin, Qian Liu, Jiake Xu, Zhen Lian, Fangming Song, Jinjian Zheng, Dantao Xie, Lingzi Chen, Xinjia Wang, Haotian Feng, Mengyu Zhou, Guanfeng Yao

Research output: Contribution to journalArticle

Abstract

Osteoporosis is a chronic bone lytic disease, because of inadequate bone ossification and/or excessive bone resorption. Even though drugs are currently available for the treatment of osteoporosis, there remains an unmet need for the development of more specific novel agents with less adverse effects. Dehydrocostus lactone (DHC), a natural sesquiterpene lactone, was previously found to affect the differentiation of inflammatory cells by inhibiting NF-κB pathways, and garnered much interest for its anti-cancer properties via SOCS-mediated cell cycle arrest and apoptosis. As NF-κB pathway plays an essential role in osteoclast differentiation, we sought to discover the biological effects of DHC on osteoclast differentiation and resorptive activity, as well as the underlying mechanisms on these effects. Our research found that DHC inhibited RANKL-induced osteoclast differentiation, bone resorption and osteoclast specific genes expression via suppression of NF-κB and NFAT signaling pathways in vitro. We further demonstrated that DHC protected against ovariectomy (OVX)-induced bone loss in mice and the protective effect was mediated at least in part through the attenuation of NF-κB signaling pathway. Thus, this study provides insight that DHC might be used as a potential pharmacological treatment for osteoporosis.

Original languageEnglish
Pages (from-to)279-289
Number of pages11
JournalBiochemical Pharmacology
Volume163
DOIs
Publication statusPublished - 1 May 2019

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Osteoporosis
Osteoclasts
Bone
Estrogens
Bone Resorption
Cells
Bone and Bones
Sesquiterpenes
Bone Diseases
Ovariectomy
Lactones
Cell Cycle Checkpoints
Osteogenesis
Gene expression
Cell Differentiation
dehydrocostus lactone
Pharmacology
Apoptosis
Gene Expression
Research

Cite this

Li, Zhaoning ; Yuan, Guixin ; Lin, Xixi ; Liu, Qian ; Xu, Jiake ; Lian, Zhen ; Song, Fangming ; Zheng, Jinjian ; Xie, Dantao ; Chen, Lingzi ; Wang, Xinjia ; Feng, Haotian ; Zhou, Mengyu ; Yao, Guanfeng. / Dehydrocostus lactone (DHC) suppresses estrogen deficiency-induced osteoporosis. In: Biochemical Pharmacology. 2019 ; Vol. 163. pp. 279-289.
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Li, Z, Yuan, G, Lin, X, Liu, Q, Xu, J, Lian, Z, Song, F, Zheng, J, Xie, D, Chen, L, Wang, X, Feng, H, Zhou, M & Yao, G 2019, 'Dehydrocostus lactone (DHC) suppresses estrogen deficiency-induced osteoporosis' Biochemical Pharmacology, vol. 163, pp. 279-289. https://doi.org/10.1016/j.bcp.2019.02.002

Dehydrocostus lactone (DHC) suppresses estrogen deficiency-induced osteoporosis. / Li, Zhaoning; Yuan, Guixin; Lin, Xixi; Liu, Qian; Xu, Jiake; Lian, Zhen; Song, Fangming; Zheng, Jinjian; Xie, Dantao; Chen, Lingzi; Wang, Xinjia; Feng, Haotian; Zhou, Mengyu; Yao, Guanfeng.

In: Biochemical Pharmacology, Vol. 163, 01.05.2019, p. 279-289.

Research output: Contribution to journalArticle

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AU - Li, Zhaoning

AU - Yuan, Guixin

AU - Lin, Xixi

AU - Liu, Qian

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AU - Song, Fangming

AU - Zheng, Jinjian

AU - Xie, Dantao

AU - Chen, Lingzi

AU - Wang, Xinjia

AU - Feng, Haotian

AU - Zhou, Mengyu

AU - Yao, Guanfeng

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N2 - Osteoporosis is a chronic bone lytic disease, because of inadequate bone ossification and/or excessive bone resorption. Even though drugs are currently available for the treatment of osteoporosis, there remains an unmet need for the development of more specific novel agents with less adverse effects. Dehydrocostus lactone (DHC), a natural sesquiterpene lactone, was previously found to affect the differentiation of inflammatory cells by inhibiting NF-κB pathways, and garnered much interest for its anti-cancer properties via SOCS-mediated cell cycle arrest and apoptosis. As NF-κB pathway plays an essential role in osteoclast differentiation, we sought to discover the biological effects of DHC on osteoclast differentiation and resorptive activity, as well as the underlying mechanisms on these effects. Our research found that DHC inhibited RANKL-induced osteoclast differentiation, bone resorption and osteoclast specific genes expression via suppression of NF-κB and NFAT signaling pathways in vitro. We further demonstrated that DHC protected against ovariectomy (OVX)-induced bone loss in mice and the protective effect was mediated at least in part through the attenuation of NF-κB signaling pathway. Thus, this study provides insight that DHC might be used as a potential pharmacological treatment for osteoporosis.

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