Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways

Osteoclasts (OCs) play an important role in osteoporosis, a disease that is mainly characterized by bone loss. In our research, we aimed to identify novel approach for regulating osteoclastogenesis and thereby treating osteoporosis. Previous studies have set a precedent for screening traditional Chi...

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Main Authors: Mengbo Zhu, Wenbin Xu, Jiuzhou Jiang, Yining Wang, Yanjing Guo, Ruijia Yang, Yaqiong Chang, Bin Zhao, Zhenyu Wang, Jianfeng Zhang, Te Wang, Liqin Shangguan, Shaowei Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.736863/full
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spelling doaj-dabd9794504548f9ab0160756ab0bec12021-09-24T07:17:38ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-09-011210.3389/fendo.2021.736863736863Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling PathwaysMengbo Zhu0Mengbo Zhu1Wenbin Xu2Jiuzhou Jiang3Yining Wang4Yanjing Guo5Yanjing Guo6Ruijia Yang7Ruijia Yang8Yaqiong Chang9Bin Zhao10Zhenyu Wang11Jianfeng Zhang12Te Wang13Liqin Shangguan14Shaowei Wang15Shaowei Wang16Department of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, ChinaDepartment of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, ChinaDepartment of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic, Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Biochemistry, Basic Medical College, Shanxi Medical University, Taiyuan, ChinaOsteoclasts (OCs) play an important role in osteoporosis, a disease that is mainly characterized by bone loss. In our research, we aimed to identify novel approach for regulating osteoclastogenesis and thereby treating osteoporosis. Previous studies have set a precedent for screening traditional Chinese herbal extracts for effective inhibitors. Peiminine is an alkaloid extracted from the bulb of Fritillaria thunbergii Miq that reportedly has anticancer and anti-inflammatory effects. Thus, the potential inhibitory effect of peiminine on OC differentiation was investigated via a series of experiments. According to the results, peiminine downregulated the levels of specific genes and proteins in vitro and consequently suppressed OC differentiation and function. Based on these findings, we further investigated the underlying molecular mechanisms and identified the NF-κB and ERK1/2 signaling pathways as potential targets of peiminine. In vivo, peiminine alleviated bone loss in an ovariectomized mouse model.https://www.frontiersin.org/articles/10.3389/fendo.2021.736863/fullpeiminineosteoclastNFATc1NF-κBosteoporosis
collection DOAJ
language English
format Article
sources DOAJ
author Mengbo Zhu
Mengbo Zhu
Wenbin Xu
Jiuzhou Jiang
Yining Wang
Yanjing Guo
Yanjing Guo
Ruijia Yang
Ruijia Yang
Yaqiong Chang
Bin Zhao
Zhenyu Wang
Jianfeng Zhang
Te Wang
Liqin Shangguan
Shaowei Wang
Shaowei Wang
spellingShingle Mengbo Zhu
Mengbo Zhu
Wenbin Xu
Jiuzhou Jiang
Yining Wang
Yanjing Guo
Yanjing Guo
Ruijia Yang
Ruijia Yang
Yaqiong Chang
Bin Zhao
Zhenyu Wang
Jianfeng Zhang
Te Wang
Liqin Shangguan
Shaowei Wang
Shaowei Wang
Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
Frontiers in Endocrinology
peiminine
osteoclast
NFATc1
NF-κB
osteoporosis
author_facet Mengbo Zhu
Mengbo Zhu
Wenbin Xu
Jiuzhou Jiang
Yining Wang
Yanjing Guo
Yanjing Guo
Ruijia Yang
Ruijia Yang
Yaqiong Chang
Bin Zhao
Zhenyu Wang
Jianfeng Zhang
Te Wang
Liqin Shangguan
Shaowei Wang
Shaowei Wang
author_sort Mengbo Zhu
title Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
title_short Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
title_full Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
title_fullStr Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
title_full_unstemmed Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
title_sort peiminine suppresses rankl-induced osteoclastogenesis by inhibiting the nfatc1, erk, and nf-κb signaling pathways
publisher Frontiers Media S.A.
series Frontiers in Endocrinology
issn 1664-2392
publishDate 2021-09-01
description Osteoclasts (OCs) play an important role in osteoporosis, a disease that is mainly characterized by bone loss. In our research, we aimed to identify novel approach for regulating osteoclastogenesis and thereby treating osteoporosis. Previous studies have set a precedent for screening traditional Chinese herbal extracts for effective inhibitors. Peiminine is an alkaloid extracted from the bulb of Fritillaria thunbergii Miq that reportedly has anticancer and anti-inflammatory effects. Thus, the potential inhibitory effect of peiminine on OC differentiation was investigated via a series of experiments. According to the results, peiminine downregulated the levels of specific genes and proteins in vitro and consequently suppressed OC differentiation and function. Based on these findings, we further investigated the underlying molecular mechanisms and identified the NF-κB and ERK1/2 signaling pathways as potential targets of peiminine. In vivo, peiminine alleviated bone loss in an ovariectomized mouse model.
topic peiminine
osteoclast
NFATc1
NF-κB
osteoporosis
url https://www.frontiersin.org/articles/10.3389/fendo.2021.736863/full
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