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The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro

Osteoprotegerin (OPG) is a new member of the tumor necrosis factor (TNF) receptor superfamily, which can inhibit the differentiation and activity of osteoclasts by binding to nuclear factor kappa B receptor activator (RANK) competitively with nuclear factor kappa B receptor activator ligand (RANKL)....

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Autores principales: Zhu, Jiaqiao, Ma, Yonggang, Wang, Jie, Wang, Yangyang, Ali, Waseem, Zou, Hui, Zhao, Hongyan, Tong, Xishuai, Song, Ruilong, Liu, Zongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861131/
https://www.ncbi.nlm.nih.gov/pubmed/36675029
http://dx.doi.org/10.3390/ijms24021518
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author Zhu, Jiaqiao
Ma, Yonggang
Wang, Jie
Wang, Yangyang
Ali, Waseem
Zou, Hui
Zhao, Hongyan
Tong, Xishuai
Song, Ruilong
Liu, Zongping
author_facet Zhu, Jiaqiao
Ma, Yonggang
Wang, Jie
Wang, Yangyang
Ali, Waseem
Zou, Hui
Zhao, Hongyan
Tong, Xishuai
Song, Ruilong
Liu, Zongping
author_sort Zhu, Jiaqiao
collection PubMed
description Osteoprotegerin (OPG) is a new member of the tumor necrosis factor (TNF) receptor superfamily, which can inhibit the differentiation and activity of osteoclasts by binding to nuclear factor kappa B receptor activator (RANK) competitively with nuclear factor kappa B receptor activator ligand (RANKL). The previous experiments found that OPG can induce apoptosis of mature osteoclasts in vitro, which can inhibit the activity of mature osteoclasts, thereby exerting its role in protecting bone tissue. In addition, pyroptosis is a new type of cell death that is different from apoptosis. It is unclear whether OPG can induce mature osteoclast pyroptosis and thereby play its role in protecting bone tissue. In this study, the results showed that compared with the control group, the survival rate of osteoclasts in the OPG group was significantly reduced, and the contents of IL-1β, IL-18, and LDH in the supernatant both increased. Many osteoclast plasma membranes were observed to rupture in bright fields, and OPG induced loss of their morphology. Flow cytometry was used to analyze the pyroptosis rate; OPG significantly increased the osteoclast pyroptosis rate. To further reveal the mechanism of OPG-induced osteoclast pyroptosis, we examined the expression level of pyroptosis-related genes and proteins, and the results found that OPG increased the expression of NLRP3, ASC, caspase-1, and GSDMD-N compared with the control group. In summary, OPG can induce osteoclast pyroptosis, and its mechanism is related to the expression levels of ASC, NLRP3, caspase 1 and GSDMD, which were included in the classical pathway of pyroptosis.
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spelling pubmed-98611312023-01-22 The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro Zhu, Jiaqiao Ma, Yonggang Wang, Jie Wang, Yangyang Ali, Waseem Zou, Hui Zhao, Hongyan Tong, Xishuai Song, Ruilong Liu, Zongping Int J Mol Sci Article Osteoprotegerin (OPG) is a new member of the tumor necrosis factor (TNF) receptor superfamily, which can inhibit the differentiation and activity of osteoclasts by binding to nuclear factor kappa B receptor activator (RANK) competitively with nuclear factor kappa B receptor activator ligand (RANKL). The previous experiments found that OPG can induce apoptosis of mature osteoclasts in vitro, which can inhibit the activity of mature osteoclasts, thereby exerting its role in protecting bone tissue. In addition, pyroptosis is a new type of cell death that is different from apoptosis. It is unclear whether OPG can induce mature osteoclast pyroptosis and thereby play its role in protecting bone tissue. In this study, the results showed that compared with the control group, the survival rate of osteoclasts in the OPG group was significantly reduced, and the contents of IL-1β, IL-18, and LDH in the supernatant both increased. Many osteoclast plasma membranes were observed to rupture in bright fields, and OPG induced loss of their morphology. Flow cytometry was used to analyze the pyroptosis rate; OPG significantly increased the osteoclast pyroptosis rate. To further reveal the mechanism of OPG-induced osteoclast pyroptosis, we examined the expression level of pyroptosis-related genes and proteins, and the results found that OPG increased the expression of NLRP3, ASC, caspase-1, and GSDMD-N compared with the control group. In summary, OPG can induce osteoclast pyroptosis, and its mechanism is related to the expression levels of ASC, NLRP3, caspase 1 and GSDMD, which were included in the classical pathway of pyroptosis. MDPI 2023-01-12 /pmc/articles/PMC9861131/ /pubmed/36675029 http://dx.doi.org/10.3390/ijms24021518 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhu, Jiaqiao
Ma, Yonggang
Wang, Jie
Wang, Yangyang
Ali, Waseem
Zou, Hui
Zhao, Hongyan
Tong, Xishuai
Song, Ruilong
Liu, Zongping
The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro
title The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro
title_full The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro
title_fullStr The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro
title_full_unstemmed The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro
title_short The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro
title_sort mechanism of osteoprotegerin-induced osteoclast pyroptosis in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861131/
https://www.ncbi.nlm.nih.gov/pubmed/36675029
http://dx.doi.org/10.3390/ijms24021518
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