Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis

Haiming Jin, Qingqing Wang, Kai Chen, Ke Xu, Hao Pan, Feifan Chu, Zhen Ye, Ziyi Wang, Jennifer Tickner, Heng Qiu, Chao Wang, Jacob Kenny, Huazi Xu, Te Wang, Jiake Xu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin β3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.

Original languageEnglish
Pages (from-to)8355-8368
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number12
DOIs
Publication statusPublished - 1 Dec 2019

Fingerprint

Osteogenesis
Bone and Bones
Osteoclasts
Osteoporosis
Bone Diseases
Therapeutic Uses
Bone Resorption
Integrins
Adenosine Triphosphatases
Anti-Inflammatory Agents
Transcription Factors
Antioxidants
astilbin
Proteins
Therapeutics

Cite this

Jin, Haiming ; Wang, Qingqing ; Chen, Kai ; Xu, Ke ; Pan, Hao ; Chu, Feifan ; Ye, Zhen ; Wang, Ziyi ; Tickner, Jennifer ; Qiu, Heng ; Wang, Chao ; Kenny, Jacob ; Xu, Huazi ; Wang, Te ; Xu, Jiake. / Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis. In: Journal of Cellular and Molecular Medicine. 2019 ; Vol. 23, No. 12. pp. 8355-8368.
@article{42979cd1fd0445e6add77b94f9556209,
title = "Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis",
abstract = "Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin β3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.",
keywords = "Astilbin, bone resorption, osteoclast, osteoclastogenesis, osteoporosis, RANKL",
author = "Haiming Jin and Qingqing Wang and Kai Chen and Ke Xu and Hao Pan and Feifan Chu and Zhen Ye and Ziyi Wang and Jennifer Tickner and Heng Qiu and Chao Wang and Jacob Kenny and Huazi Xu and Te Wang and Jiake Xu",
year = "2019",
month = "12",
day = "1",
doi = "10.1111/jcmm.14713",
language = "English",
volume = "23",
pages = "8355--8368",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "12",

}

Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis. / Jin, Haiming; Wang, Qingqing; Chen, Kai; Xu, Ke; Pan, Hao; Chu, Feifan; Ye, Zhen; Wang, Ziyi; Tickner, Jennifer; Qiu, Heng; Wang, Chao; Kenny, Jacob; Xu, Huazi; Wang, Te; Xu, Jiake.

In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 12, 01.12.2019, p. 8355-8368.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL-induced osteoclastogenesis

AU - Jin, Haiming

AU - Wang, Qingqing

AU - Chen, Kai

AU - Xu, Ke

AU - Pan, Hao

AU - Chu, Feifan

AU - Ye, Zhen

AU - Wang, Ziyi

AU - Tickner, Jennifer

AU - Qiu, Heng

AU - Wang, Chao

AU - Kenny, Jacob

AU - Xu, Huazi

AU - Wang, Te

AU - Xu, Jiake

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin β3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.

AB - Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin β3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.

KW - Astilbin

KW - bone resorption

KW - osteoclast

KW - osteoclastogenesis

KW - osteoporosis

KW - RANKL

UR - http://www.scopus.com/inward/record.url?scp=85074010083&partnerID=8YFLogxK

U2 - 10.1111/jcmm.14713

DO - 10.1111/jcmm.14713

M3 - Article

VL - 23

SP - 8355

EP - 8368

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 12

ER -