Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.

<h4>Background</h4>Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the os...

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Autores principales:	Guillaume Mabilleau, Afsie Sabokbar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8f089eeaf8448e3bc8fe2b9b0aa2d38
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spelling	oai:doaj.org-article:d8f089eeaf8448e3bc8fe2b9b0aa2d382021-11-25T06:17:48ZInterleukin-32 promotes osteoclast differentiation but not osteoclast activation.1932-620310.1371/journal.pone.0004173https://doaj.org/article/d8f089eeaf8448e3bc8fe2b9b0aa2d382009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19137064/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear.<h4>Methodology/principal findings</h4>In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly generated osteoclast was increased, a significant decrease of the percentage of lacunar resorption was evident suggesting a possible inhibitory effect of this cytokine on osteoclast activation. To determine the mechanism by which IL-32 induces such response, we sought to determine the intracellular pathways activated and the release of soluble mediators in response to IL-32. Our results indicated that compared to RANKL, IL-32 induced a massive activation of ERK1/2 and Akt. Moreover, IL-32 was also capable of stimulating the release of IL-4 and IFN-gamma, two known inhibitors of osteoclast formation and activation.<h4>Conclusions/significance</h4>This is the first in vitro report on the complex role of IL-32 on osteoclast precursors. Further clarification on the exact role of IL-32 in vivo is required prior to the development of any potential therapeutic approach.Guillaume MabilleauAfsie SabokbarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 1, p e4173 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guillaume Mabilleau Afsie Sabokbar Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
description	<h4>Background</h4>Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear.<h4>Methodology/principal findings</h4>In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly generated osteoclast was increased, a significant decrease of the percentage of lacunar resorption was evident suggesting a possible inhibitory effect of this cytokine on osteoclast activation. To determine the mechanism by which IL-32 induces such response, we sought to determine the intracellular pathways activated and the release of soluble mediators in response to IL-32. Our results indicated that compared to RANKL, IL-32 induced a massive activation of ERK1/2 and Akt. Moreover, IL-32 was also capable of stimulating the release of IL-4 and IFN-gamma, two known inhibitors of osteoclast formation and activation.<h4>Conclusions/significance</h4>This is the first in vitro report on the complex role of IL-32 on osteoclast precursors. Further clarification on the exact role of IL-32 in vivo is required prior to the development of any potential therapeutic approach.
format	article
author	Guillaume Mabilleau Afsie Sabokbar
author_facet	Guillaume Mabilleau Afsie Sabokbar
author_sort	Guillaume Mabilleau
title	Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
title_short	Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
title_full	Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
title_fullStr	Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
title_full_unstemmed	Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
title_sort	interleukin-32 promotes osteoclast differentiation but not osteoclast activation.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/d8f089eeaf8448e3bc8fe2b9b0aa2d38
work_keys_str_mv	AT guillaumemabilleau interleukin32promotesosteoclastdifferentiationbutnotosteoclastactivation AT afsiesabokbar interleukin32promotesosteoclastdifferentiationbutnotosteoclastactivation
_version_	1718413956188471296

Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.

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