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Article

The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro

by
Jiaqiao Zhu
1,2,3,†,
Yonggang Ma
1,2,3,†,
Jie Wang
1,2,3,
Yangyang Wang
1,2,3,
Waseem Ali
1,2,3,
Hui Zou
1,2,3,
Hongyan Zhao
1,2,3,
Xishuai Tong
1,2,3,
Ruilong Song
1,2,3 and
Zongping Liu
1,2,3,*
1
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
2
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
3
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2023, 24(2), 1518; https://doi.org/10.3390/ijms24021518
Submission received: 1 December 2022 / Revised: 4 January 2023 / Accepted: 9 January 2023 / Published: 12 January 2023
(This article belongs to the Special Issue Advance in Bone Biology)
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Abstract

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.
Keywords: osteoprotegrin; osteoclast; pyroptosis; GSDMD osteoprotegrin; osteoclast; pyroptosis; GSDMD

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MDPI and ACS Style

Zhu, J.; Ma, Y.; Wang, J.; Wang, Y.; Ali, W.; Zou, H.; Zhao, H.; Tong, X.; Song, R.; Liu, Z. The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro. Int. J. Mol. Sci. 2023, 24, 1518. https://doi.org/10.3390/ijms24021518

AMA Style

Zhu J, Ma Y, Wang J, Wang Y, Ali W, Zou H, Zhao H, Tong X, Song R, Liu Z. The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro. International Journal of Molecular Sciences. 2023; 24(2):1518. https://doi.org/10.3390/ijms24021518

Chicago/Turabian Style

Zhu, Jiaqiao, Yonggang Ma, Jie Wang, Yangyang Wang, Waseem Ali, Hui Zou, Hongyan Zhao, Xishuai Tong, Ruilong Song, and Zongping Liu. 2023. "The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro" International Journal of Molecular Sciences 24, no. 2: 1518. https://doi.org/10.3390/ijms24021518

APA Style

Zhu, J., Ma, Y., Wang, J., Wang, Y., Ali, W., Zou, H., Zhao, H., Tong, X., Song, R., & Liu, Z. (2023). The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro. International Journal of Molecular Sciences, 24(2), 1518. https://doi.org/10.3390/ijms24021518

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