Madecassoside inhibits estrogen deficiency-induced osteoporosis by suppressing RANKL-induced osteoclastogenesis

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

Research output: Contribution to journalArticle

2 Citations (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. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti-inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA 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, ATP6V0D2/V-ATPase-d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses 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, MA might be a potential candidate for treating osteolytic bone diseases.

Original languageEnglish
Pages (from-to)380-394
Number of pages15
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2019

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

Cite this

Wang, Qingqing ; Yao, Lingya ; Xu, Ke ; Jin, Haiming ; Chen, Kai ; Wang, Ziyi ; Liu, Qian ; Cao, Zhen ; Kenny, Jacob ; Liu, Yuhao ; Tickner, Jennifer ; Xu, Huazi ; Xu, Jiake. / Madecassoside inhibits estrogen deficiency-induced osteoporosis by suppressing RANKL-induced osteoclastogenesis. In: Journal of Cellular and Molecular Medicine. 2019 ; Vol. 23, No. 1. pp. 380-394.
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title = "Madecassoside inhibits estrogen deficiency-induced osteoporosis by suppressing 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. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti-inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA 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, ATP6V0D2/V-ATPase-d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses 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, MA might be a potential candidate for treating osteolytic bone diseases.",
author = "Qingqing Wang and Lingya Yao and Ke Xu and Haiming Jin and Kai Chen and Ziyi Wang and Qian Liu and Zhen Cao and Jacob Kenny and Yuhao Liu and Jennifer Tickner and Huazi Xu and Jiake Xu",
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Madecassoside inhibits estrogen deficiency-induced osteoporosis by suppressing RANKL-induced osteoclastogenesis. / Wang, Qingqing; Yao, Lingya; Xu, Ke; Jin, Haiming; Chen, Kai; Wang, Ziyi; Liu, Qian; Cao, Zhen; Kenny, Jacob; Liu, Yuhao; Tickner, Jennifer; Xu, Huazi; Xu, Jiake.

In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 1, 01.2019, p. 380-394.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Madecassoside inhibits estrogen deficiency-induced osteoporosis by suppressing RANKL-induced osteoclastogenesis

AU - Wang, Qingqing

AU - Yao, Lingya

AU - Xu, Ke

AU - Jin, Haiming

AU - Chen, Kai

AU - Wang, Ziyi

AU - Liu, Qian

AU - Cao, Zhen

AU - Kenny, Jacob

AU - Liu, Yuhao

AU - Tickner, Jennifer

AU - Xu, Huazi

AU - Xu, Jiake

PY - 2019/1

Y1 - 2019/1

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. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti-inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA 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, ATP6V0D2/V-ATPase-d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses 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, MA 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. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti-inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA 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, ATP6V0D2/V-ATPase-d2, and integrin β3). Furthermore, we examined the underlying mechanisms and found that MA represses 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, MA might be a potential candidate for treating osteolytic bone diseases.

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DO - 10.1111/jcmm.13942

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EP - 394

JO - Journal of Cellular and Molecular Medicine

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