Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation

Abstract The NLRP3 inflammasome senses a variety of signals referred to as danger associated molecular patterns (DAMPs), including those triggered by crystalline particulates or degradation products of extracellular matrix. Since some DAMPs confer tissue-specific activation of the inflammasomes, we...

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Autores principales:	Yael Alippe, Chun Wang, Biancamaria Ricci, Jianqiu Xiao, Chao Qu, Wei Zou, Deborah V. Novack, Yousef Abu-Amer, Roberto Civitelli, Gabriel Mbalaviele
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f52ad37df2334b81a1175e640425d4a4
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spelling	oai:doaj.org-article:f52ad37df2334b81a1175e640425d4a42021-12-02T15:05:08ZBone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation10.1038/s41598-017-07014-02045-2322https://doaj.org/article/f52ad37df2334b81a1175e640425d4a42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07014-0https://doaj.org/toc/2045-2322Abstract The NLRP3 inflammasome senses a variety of signals referred to as danger associated molecular patterns (DAMPs), including those triggered by crystalline particulates or degradation products of extracellular matrix. Since some DAMPs confer tissue-specific activation of the inflammasomes, we tested the hypothesis that bone matrix components function as DAMPs for the NLRP3 inflammasome and regulate osteoclast differentiation. Indeed, bone particles cause exuberant osteoclastogenesis in the presence of RANKL, a response that correlates with NLRP3 abundance and the state of inflammasome activation. To determine the relevance of these findings to bone homeostasis, we studied the impact of Nlrp3 deficiency on bone using pre-clinical mouse models of high bone turnover, including estrogen deficiency and sustained exposure to parathyroid hormone or RANKL. Despite comparable baseline indices of bone mass, bone loss caused by hormonal or RANKL perturbations is significantly reduced in Nlrp3 deficient than in wild type mice. Consistent with the notion that osteolysis releases DAMPs from bone matrix, pharmacologic inhibition of bone resorption by zoledronate attenuates inflammasome activation in mice. Thus, signals originating from bone matrix activate the NLRP3 inflammasome in the osteoclast lineage, and may represent a bone-restricted positive feedback mechanism that amplifies bone resorption in pathologic conditions of accelerated bone turnover.Yael AlippeChun WangBiancamaria RicciJianqiu XiaoChao QuWei ZouDeborah V. NovackYousef Abu-AmerRoberto CivitelliGabriel MbalavieleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yael Alippe Chun Wang Biancamaria Ricci Jianqiu Xiao Chao Qu Wei Zou Deborah V. Novack Yousef Abu-Amer Roberto Civitelli Gabriel Mbalaviele Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation
description	Abstract The NLRP3 inflammasome senses a variety of signals referred to as danger associated molecular patterns (DAMPs), including those triggered by crystalline particulates or degradation products of extracellular matrix. Since some DAMPs confer tissue-specific activation of the inflammasomes, we tested the hypothesis that bone matrix components function as DAMPs for the NLRP3 inflammasome and regulate osteoclast differentiation. Indeed, bone particles cause exuberant osteoclastogenesis in the presence of RANKL, a response that correlates with NLRP3 abundance and the state of inflammasome activation. To determine the relevance of these findings to bone homeostasis, we studied the impact of Nlrp3 deficiency on bone using pre-clinical mouse models of high bone turnover, including estrogen deficiency and sustained exposure to parathyroid hormone or RANKL. Despite comparable baseline indices of bone mass, bone loss caused by hormonal or RANKL perturbations is significantly reduced in Nlrp3 deficient than in wild type mice. Consistent with the notion that osteolysis releases DAMPs from bone matrix, pharmacologic inhibition of bone resorption by zoledronate attenuates inflammasome activation in mice. Thus, signals originating from bone matrix activate the NLRP3 inflammasome in the osteoclast lineage, and may represent a bone-restricted positive feedback mechanism that amplifies bone resorption in pathologic conditions of accelerated bone turnover.
format	article
author	Yael Alippe Chun Wang Biancamaria Ricci Jianqiu Xiao Chao Qu Wei Zou Deborah V. Novack Yousef Abu-Amer Roberto Civitelli Gabriel Mbalaviele
author_facet	Yael Alippe Chun Wang Biancamaria Ricci Jianqiu Xiao Chao Qu Wei Zou Deborah V. Novack Yousef Abu-Amer Roberto Civitelli Gabriel Mbalaviele
author_sort	Yael Alippe
title	Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation
title_short	Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation
title_full	Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation
title_fullStr	Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation
title_full_unstemmed	Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation
title_sort	bone matrix components activate the nlrp3 inflammasome and promote osteoclast differentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f52ad37df2334b81a1175e640425d4a4
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Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation

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