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Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that ac...

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Autores principales: Xue, Chunchun, Luo, Huan, Wang, Libo, Deng, Qing, Kui, Wenyun, Da, Weiwei, Chen, Lin, Liu, Shuang, Xue, Yongpeng, Yang, Jiafan, Li, Lingxing, Du, Wenlan, Shi, Qi, Li, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682992/
https://www.ncbi.nlm.nih.gov/pubmed/38034017
http://dx.doi.org/10.3389/fendo.2023.1234563
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author Xue, Chunchun
Luo, Huan
Wang, Libo
Deng, Qing
Kui, Wenyun
Da, Weiwei
Chen, Lin
Liu, Shuang
Xue, Yongpeng
Yang, Jiafan
Li, Lingxing
Du, Wenlan
Shi, Qi
Li, Xiaofeng
author_facet Xue, Chunchun
Luo, Huan
Wang, Libo
Deng, Qing
Kui, Wenyun
Da, Weiwei
Chen, Lin
Liu, Shuang
Xue, Yongpeng
Yang, Jiafan
Li, Lingxing
Du, Wenlan
Shi, Qi
Li, Xiaofeng
author_sort Xue, Chunchun
collection PubMed
description Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.
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spelling pubmed-106829922023-11-30 Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling Xue, Chunchun Luo, Huan Wang, Libo Deng, Qing Kui, Wenyun Da, Weiwei Chen, Lin Liu, Shuang Xue, Yongpeng Yang, Jiafan Li, Lingxing Du, Wenlan Shi, Qi Li, Xiaofeng Front Endocrinol (Lausanne) Endocrinology Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation. Frontiers Media S.A. 2023-11-13 /pmc/articles/PMC10682992/ /pubmed/38034017 http://dx.doi.org/10.3389/fendo.2023.1234563 Text en Copyright © 2023 Xue, Luo, Wang, Deng, Kui, Da, Chen, Liu, Xue, Yang, Li, Du, Shi and Li 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 Endocrinology
Xue, Chunchun
Luo, Huan
Wang, Libo
Deng, Qing
Kui, Wenyun
Da, Weiwei
Chen, Lin
Liu, Shuang
Xue, Yongpeng
Yang, Jiafan
Li, Lingxing
Du, Wenlan
Shi, Qi
Li, Xiaofeng
Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
title Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
title_full Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
title_fullStr Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
title_full_unstemmed Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
title_short Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling
title_sort aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting nf-κb signaling
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682992/
https://www.ncbi.nlm.nih.gov/pubmed/38034017
http://dx.doi.org/10.3389/fendo.2023.1234563
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