The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts

Abstract Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts....

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Autores principales:	Hyunsoo Kim, Matthew C. Walsh, Noriko Takegahara, Sarah A. Middleton, Hong-In Shin, Junhyong Kim, Yongwon Choi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/570b4bebfc7a4da78d4458ebaf52f774
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spelling	oai:doaj.org-article:570b4bebfc7a4da78d4458ebaf52f7742021-12-02T16:06:56ZThe purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts10.1038/s41598-017-00139-22045-2322https://doaj.org/article/570b4bebfc7a4da78d4458ebaf52f7742017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00139-2https://doaj.org/toc/2045-2322Abstract Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs. We further demonstrate that P2X5 is required for ATP-mediated inflammasome activation and IL-1β production by OCs, and that P2X5-deficient OC maturation is rescued in vitro by addition of exogenous IL-1β. These findings identify a mechanism by which OCs react to inflammatory stimuli, and may identify purinergic signaling as a therapeutic target for bone loss-related inflammatory conditions.Hyunsoo KimMatthew C. WalshNoriko TakegaharaSarah A. MiddletonHong-In ShinJunhyong KimYongwon ChoiNature 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 Hyunsoo Kim Matthew C. Walsh Noriko Takegahara Sarah A. Middleton Hong-In Shin Junhyong Kim Yongwon Choi The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
description	Abstract Excessive bone resorption by osteoclasts (OCs) can result in serious clinical outcomes, including bone loss that may weaken skeletal or periodontal strength. Proper bone homeostasis and skeletal strength are maintained by balancing OC function with the bone-forming function of osteoblasts. Unfortunately, current treatments that broadly inhibit OC differentiation or function may also interfere with coupled bone formation. We therefore identified a factor, the purinergic receptor P2X5 that is highly expressed during the OC maturation phase, and which we show here plays no apparent role in early bone development and homeostasis, but which is required for osteoclast-mediated inflammatory bone loss and hyper-multinucleation of OCs. We further demonstrate that P2X5 is required for ATP-mediated inflammasome activation and IL-1β production by OCs, and that P2X5-deficient OC maturation is rescued in vitro by addition of exogenous IL-1β. These findings identify a mechanism by which OCs react to inflammatory stimuli, and may identify purinergic signaling as a therapeutic target for bone loss-related inflammatory conditions.
format	article
author	Hyunsoo Kim Matthew C. Walsh Noriko Takegahara Sarah A. Middleton Hong-In Shin Junhyong Kim Yongwon Choi
author_facet	Hyunsoo Kim Matthew C. Walsh Noriko Takegahara Sarah A. Middleton Hong-In Shin Junhyong Kim Yongwon Choi
author_sort	Hyunsoo Kim
title	The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
title_short	The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
title_full	The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
title_fullStr	The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
title_full_unstemmed	The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
title_sort	purinergic receptor p2x5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/570b4bebfc7a4da78d4458ebaf52f774
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The purinergic receptor P2X5 regulates inflammasome activity and hyper-multinucleation of murine osteoclasts

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