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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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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. |
format | Online Article Text |
id | pubmed-10682992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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