Evodiamine inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in mice

Haiming Jin, Lingya Yao, Kai Chen, Yuhao Liu, Qingqing Wang, Ziyi Wang, Qian Liu, Zhen Cao, Jacob Kenny, Jennifer Tickner, Xiangyang Wang, Jiake Xu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Postmenopausal osteoporosis (PMO) is a progressive bone disease characterized by the over-production and activation of osteoclasts in elderly women. In our study, we investigated the anti-osteoclastogenic effect of evodiamine (EVO) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage (BMM)-derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF-κB ligand (RANKL)-induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL-induced transcriptional activity of IκBα. RANKL-induced Ca2+ oscillations were also abrogated by EVO. In vivo, an ovariectomized (OVX) mouse model was established to mimic PMO, and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL-induced osteoclastogenesis through NF-κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO.

Original languageEnglish
Pages (from-to)522-534
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2019

Fingerprint

Ovariectomy
Osteogenesis
Bone and Bones
Osteoclasts
Postmenopausal Osteoporosis
Calcium Signaling
Bone Diseases
Durapatite
evodiamine
Oral Administration
Macrophages
Ligands
Gene Expression
Proteins

Cite this

Jin, Haiming ; Yao, Lingya ; Chen, Kai ; Liu, Yuhao ; Wang, Qingqing ; Wang, Ziyi ; Liu, Qian ; Cao, Zhen ; Kenny, Jacob ; Tickner, Jennifer ; Wang, Xiangyang ; Xu, Jiake. / Evodiamine inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in mice. In: Journal of Cellular and Molecular Medicine. 2019 ; Vol. 23, No. 1. pp. 522-534.
@article{cd3887a1f6214e84bfc00c70f12ccff7,
title = "Evodiamine inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in mice",
abstract = "Postmenopausal osteoporosis (PMO) is a progressive bone disease characterized by the over-production and activation of osteoclasts in elderly women. In our study, we investigated the anti-osteoclastogenic effect of evodiamine (EVO) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage (BMM)-derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF-κB ligand (RANKL)-induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL-induced transcriptional activity of IκBα. RANKL-induced Ca2+ oscillations were also abrogated by EVO. In vivo, an ovariectomized (OVX) mouse model was established to mimic PMO, and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL-induced osteoclastogenesis through NF-κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO.",
author = "Haiming Jin and Lingya Yao and Kai Chen and Yuhao Liu and Qingqing Wang and Ziyi Wang and Qian Liu and Zhen Cao and Jacob Kenny and Jennifer Tickner and Xiangyang Wang and Jiake Xu",
year = "2019",
month = "1",
doi = "10.1111/jcmm.13955",
language = "English",
volume = "23",
pages = "522--534",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "1",

}

Evodiamine inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in mice. / Jin, Haiming; Yao, Lingya; Chen, Kai; Liu, Yuhao; Wang, Qingqing; Wang, Ziyi; Liu, Qian; Cao, Zhen; Kenny, Jacob; Tickner, Jennifer; Wang, Xiangyang; Xu, Jiake.

In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 1, 01.2019, p. 522-534.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evodiamine inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in mice

AU - Jin, Haiming

AU - Yao, Lingya

AU - Chen, Kai

AU - Liu, Yuhao

AU - Wang, Qingqing

AU - Wang, Ziyi

AU - Liu, Qian

AU - Cao, Zhen

AU - Kenny, Jacob

AU - Tickner, Jennifer

AU - Wang, Xiangyang

AU - Xu, Jiake

PY - 2019/1

Y1 - 2019/1

N2 - Postmenopausal osteoporosis (PMO) is a progressive bone disease characterized by the over-production and activation of osteoclasts in elderly women. In our study, we investigated the anti-osteoclastogenic effect of evodiamine (EVO) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage (BMM)-derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF-κB ligand (RANKL)-induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL-induced transcriptional activity of IκBα. RANKL-induced Ca2+ oscillations were also abrogated by EVO. In vivo, an ovariectomized (OVX) mouse model was established to mimic PMO, and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL-induced osteoclastogenesis through NF-κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO.

AB - Postmenopausal osteoporosis (PMO) is a progressive bone disease characterized by the over-production and activation of osteoclasts in elderly women. In our study, we investigated the anti-osteoclastogenic effect of evodiamine (EVO) in vivo and in vitro, as well as the underlying mechanism. By using an in vitro bone marrow macrophage (BMM)-derived osteoclast culture system, we found that EVO inhibited osteoclast formation, hydroxyapatite resorption and receptor activator of NF-κB ligand (RANKL)-induced osteoclast marker gene and protein expression. Mechanistically, we found that EVO inhibited the degradation and RANKL-induced transcriptional activity of IκBα. RANKL-induced Ca2+ oscillations were also abrogated by EVO. In vivo, an ovariectomized (OVX) mouse model was established to mimic PMO, and OVX mice received oral administration of either EVO (10 mg/kg) or saline every other day. We found that EVO can attenuate bone loss in OVX mice by inhibiting osteoclastogenesis. Taken together, our findings suggest that EVO suppresses RANKL-induced osteoclastogenesis through NF-κB and calcium signalling pathways and has potential value as a therapeutic agent for PMO.

U2 - 10.1111/jcmm.13955

DO - 10.1111/jcmm.13955

M3 - Article

VL - 23

SP - 522

EP - 534

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 1

ER -