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Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling

Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated...

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Autores principales: Cao, Jinjin, Zhou, Ming-Xue, Chen, Xinyan, Sun, Menglu, Wei, Congmin, Peng, Qisheng, Cheng, Zhou, Sun, Wanchun, Wang, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087042/
https://www.ncbi.nlm.nih.gov/pubmed/35558084
http://dx.doi.org/10.3389/fimmu.2022.880988
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author Cao, Jinjin
Zhou, Ming-Xue
Chen, Xinyan
Sun, Menglu
Wei, Congmin
Peng, Qisheng
Cheng, Zhou
Sun, Wanchun
Wang, Hongbing
author_facet Cao, Jinjin
Zhou, Ming-Xue
Chen, Xinyan
Sun, Menglu
Wei, Congmin
Peng, Qisheng
Cheng, Zhou
Sun, Wanchun
Wang, Hongbing
author_sort Cao, Jinjin
collection PubMed
description Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at the middle–late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2β-Aα expression. Moreover, GSK3β inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3β, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3β, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3β inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease.
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spelling pubmed-90870422022-05-11 Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling Cao, Jinjin Zhou, Ming-Xue Chen, Xinyan Sun, Menglu Wei, Congmin Peng, Qisheng Cheng, Zhou Sun, Wanchun Wang, Hongbing Front Immunol Immunology Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at the middle–late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2β-Aα expression. Moreover, GSK3β inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3β, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3β, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3β inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease. Frontiers Media S.A. 2022-04-26 /pmc/articles/PMC9087042/ /pubmed/35558084 http://dx.doi.org/10.3389/fimmu.2022.880988 Text en Copyright © 2022 Cao, Zhou, Chen, Sun, Wei, Peng, Cheng, Sun and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cao, Jinjin
Zhou, Ming-Xue
Chen, Xinyan
Sun, Menglu
Wei, Congmin
Peng, Qisheng
Cheng, Zhou
Sun, Wanchun
Wang, Hongbing
Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
title Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
title_full Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
title_fullStr Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
title_full_unstemmed Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
title_short Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
title_sort sec-o-glucosylhamaudol inhibits rankl-induced osteoclastogenesis by repressing 5-lo and akt/gsk3β signaling
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087042/
https://www.ncbi.nlm.nih.gov/pubmed/35558084
http://dx.doi.org/10.3389/fimmu.2022.880988
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