Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells

Abstract Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and c...

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Autores principales:	Chun Wang, Can-Xin Xu, Yael Alippe, Chao Qu, Jianqiu Xiao, Ernestina Schipani, Roberto Civitelli, Yousef Abu-Amer, Gabriel Mbalaviele
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13f4d71f788e4c60923f5962ac917d93
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spelling	oai:doaj.org-article:13f4d71f788e4c60923f5962ac917d932021-12-02T16:06:28ZChronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells10.1038/s41598-017-05033-52045-2322https://doaj.org/article/13f4d71f788e4c60923f5962ac917d932017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05033-5https://doaj.org/toc/2045-2322Abstract Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.Chun WangCan-Xin XuYael AlippeChao QuJianqiu XiaoErnestina SchipaniRoberto CivitelliYousef Abu-AmerGabriel MbalavieleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chun Wang Can-Xin Xu Yael Alippe Chao Qu Jianqiu Xiao Ernestina Schipani Roberto Civitelli Yousef Abu-Amer Gabriel Mbalaviele Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
description	Abstract Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.
format	article
author	Chun Wang Can-Xin Xu Yael Alippe Chao Qu Jianqiu Xiao Ernestina Schipani Roberto Civitelli Yousef Abu-Amer Gabriel Mbalaviele
author_facet	Chun Wang Can-Xin Xu Yael Alippe Chao Qu Jianqiu Xiao Ernestina Schipani Roberto Civitelli Yousef Abu-Amer Gabriel Mbalaviele
author_sort	Chun Wang
title	Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
title_short	Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
title_full	Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
title_fullStr	Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
title_full_unstemmed	Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
title_sort	chronic inflammation triggered by the nlrp3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/13f4d71f788e4c60923f5962ac917d93
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Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells

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