Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also impos...

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Main Authors: Xue Yang, Jiamin Liang, Ziyi Wang, Yuangang Su, Yunfei Zhan, Zuoxing Wu, Jing Li, Xuedong Li, Runfeng Chen, Jinmin Zhao, Jiake Xu, Qian Liu, Bo Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.664697/full
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author Xue Yang
Jiamin Liang
Ziyi Wang
Yuangang Su
Yunfei Zhan
Zuoxing Wu
Jing Li
Xuedong Li
Runfeng Chen
Jinmin Zhao
Jinmin Zhao
Jiake Xu
Jiake Xu
Qian Liu
Bo Zhou
author_facet Xue Yang
Jiamin Liang
Ziyi Wang
Yuangang Su
Yunfei Zhan
Zuoxing Wu
Jing Li
Xuedong Li
Runfeng Chen
Jinmin Zhao
Jinmin Zhao
Jiake Xu
Jiake Xu
Qian Liu
Bo Zhou
author_sort Xue Yang
collection DOAJ
description This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.
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spelling doaj.art-d62703e8257a466fb6601b634f4440052022-12-21T20:08:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-06-011210.3389/fphar.2021.664697664697Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling PathwaysXue Yang0Jiamin Liang1Ziyi Wang2Yuangang Su3Yunfei Zhan4Zuoxing Wu5Jing Li6Xuedong Li7Runfeng Chen8Jinmin Zhao9Jinmin Zhao10Jiake Xu11Jiake Xu12Qian Liu13Bo Zhou14Guangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaSchool of Biomedical Sciences, The University of WA, Perth, WA, AustraliaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaJiu Jiang No. 1 People’s Hospital, Jiangxi, ChinaDepartment of Nuclear Medicine, School of Medicine, Zhongshan Hospital, Xiamen University, Fujian, ChinaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaResearch Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi, ChinaSchool of Biomedical Sciences, The University of WA, Perth, WA, AustraliaResearch Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi, ChinaResearch Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi, ChinaGuangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, ChinaThis article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.https://www.frontiersin.org/articles/10.3389/fphar.2021.664697/fullsesamolinNF-κBMAPKosteoclastpostmenopausal osteoporosis
spellingShingle Xue Yang
Jiamin Liang
Ziyi Wang
Yuangang Su
Yunfei Zhan
Zuoxing Wu
Jing Li
Xuedong Li
Runfeng Chen
Jinmin Zhao
Jinmin Zhao
Jiake Xu
Jiake Xu
Qian Liu
Bo Zhou
Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
Frontiers in Pharmacology
sesamolin
NF-κB
MAPK
osteoclast
postmenopausal osteoporosis
title Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
title_full Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
title_fullStr Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
title_full_unstemmed Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
title_short Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways
title_sort sesamolin protects mice from ovariectomized bone loss by inhibiting osteoclastogenesis and rankl mediated nf κb and mapk signaling pathways
topic sesamolin
NF-κB
MAPK
osteoclast
postmenopausal osteoporosis
url https://www.frontiersin.org/articles/10.3389/fphar.2021.664697/full
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