The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis

Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1β via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of c...

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Autores principales:	Megumi Mae, Mohammad Ibtehaz Alam, Yasunori Yamashita, Yukio Ozaki, Kanako Higuchi, S. M. Ziauddin, Jorge Luis Montenegro Raudales, Eiko Sakai, Takayuki Tsukuba, Atsutoshi Yoshimura
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	dental calculus NLRP3 inflammasome IL-1β IL-18 osteoclast Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/60feb19b9f094e76a3b0fa941dedda72
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spelling	oai:doaj.org-article:60feb19b9f094e76a3b0fa941dedda722021-11-25T17:56:36ZThe Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis10.3390/ijms2222124341422-00671661-6596https://doaj.org/article/60feb19b9f094e76a3b0fa941dedda722021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12434https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1β via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of cytokines produced by mouse macrophages stimulated with DC on osteoclastogenesis. The culture supernatants from wild-type (WT) mouse macrophages stimulated with DC accelerated osteoclastogenesis in RANKL-primed mouse bone marrow macrophages (BMMs), but inhibited osteoclastogenesis in RANKL-primed RAW-D cells. WT, but not NLRP3-deficient, mouse macrophages stimulated with DC produced IL-1β and IL-18 in a dose-dependent manner, indicating the NLRP3 inflammasome-dependent production of IL-1β and IL-18. Both WT and NLRP3-deficient mouse macrophages stimulated with DC produced IL-10, indicating the NLRP3 inflammasome-independent production of IL-10. Recombinant IL-1β accelerated osteoclastogenesis in both RANKL-primed BMMs and RAW-D cells, whereas recombinant IL-18 and IL-10 inhibited osteoclastogenesis. These results indicate that DC induces osteoclastogenic IL-1β in an NLRP3 inflammasome-dependent manner and anti-osteogenic IL-18 and IL-10 dependently and independently of the NLRP3 inflammasome, respectively. DC may promote alveolar bone resorption via IL-1β induction in periodontitis patients, but suppress resorption via IL-18 and IL-10 induction in some circumstances.Megumi MaeMohammad Ibtehaz AlamYasunori YamashitaYukio OzakiKanako HiguchiS. M. ZiauddinJorge Luis Montenegro RaudalesEiko SakaiTakayuki TsukubaAtsutoshi YoshimuraMDPI AGarticledental calculusNLRP3 inflammasomeIL-1βIL-18osteoclastBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12434, p 12434 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dental calculus NLRP3 inflammasome IL-1β IL-18 osteoclast Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	dental calculus NLRP3 inflammasome IL-1β IL-18 osteoclast Biology (General) QH301-705.5 Chemistry QD1-999 Megumi Mae Mohammad Ibtehaz Alam Yasunori Yamashita Yukio Ozaki Kanako Higuchi S. M. Ziauddin Jorge Luis Montenegro Raudales Eiko Sakai Takayuki Tsukuba Atsutoshi Yoshimura The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis
description	Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1β via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of cytokines produced by mouse macrophages stimulated with DC on osteoclastogenesis. The culture supernatants from wild-type (WT) mouse macrophages stimulated with DC accelerated osteoclastogenesis in RANKL-primed mouse bone marrow macrophages (BMMs), but inhibited osteoclastogenesis in RANKL-primed RAW-D cells. WT, but not NLRP3-deficient, mouse macrophages stimulated with DC produced IL-1β and IL-18 in a dose-dependent manner, indicating the NLRP3 inflammasome-dependent production of IL-1β and IL-18. Both WT and NLRP3-deficient mouse macrophages stimulated with DC produced IL-10, indicating the NLRP3 inflammasome-independent production of IL-10. Recombinant IL-1β accelerated osteoclastogenesis in both RANKL-primed BMMs and RAW-D cells, whereas recombinant IL-18 and IL-10 inhibited osteoclastogenesis. These results indicate that DC induces osteoclastogenic IL-1β in an NLRP3 inflammasome-dependent manner and anti-osteogenic IL-18 and IL-10 dependently and independently of the NLRP3 inflammasome, respectively. DC may promote alveolar bone resorption via IL-1β induction in periodontitis patients, but suppress resorption via IL-18 and IL-10 induction in some circumstances.
format	article
author	Megumi Mae Mohammad Ibtehaz Alam Yasunori Yamashita Yukio Ozaki Kanako Higuchi S. M. Ziauddin Jorge Luis Montenegro Raudales Eiko Sakai Takayuki Tsukuba Atsutoshi Yoshimura
author_facet	Megumi Mae Mohammad Ibtehaz Alam Yasunori Yamashita Yukio Ozaki Kanako Higuchi S. M. Ziauddin Jorge Luis Montenegro Raudales Eiko Sakai Takayuki Tsukuba Atsutoshi Yoshimura
author_sort	Megumi Mae
title	The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis
title_short	The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis
title_full	The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis
title_fullStr	The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis
title_full_unstemmed	The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis
title_sort	role of cytokines produced via the nlrp3 inflammasome in mouse macrophages stimulated with dental calculus in osteoclastogenesis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/60feb19b9f094e76a3b0fa941dedda72
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The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis

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