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Reference: Guillaume Mabilleau and Afsie Sabokbar, (2009). Interleukin-32 promotes osteoclast differentiation but not osteoclast activation. PLoS ONE, 4 (1), Article: e4173.Citable link to this page:

 

Interleukin-32 promotes osteoclast differentiation but not osteoclast activation

Abstract: Background: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-γ. 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.Methodology/principal findings: 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-γ, two known inhibitors of osteoclast formation and activation.Conclusions/significance: 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.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionNotes:Citation: Mabilleau, G. & Sabokbar, A. (2009). 'Interleukin-32 promotes osteoclast differentiation but not osteoclast activation', PLoS ONE 4(1), e4173. [Available at http://www.plosone.org/]. © 2009 Mabilleau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: http://www.plos.org/

Host: PLoS ONEsee more from them

Publication Website: http://www.plosone.org

Issue Date: 2009-January

Copyright Date: 2009

pages:Article: e4173Identifiers

Doi: https://doi.org/10.1371/journal.pone.0004173

Eissn: 1932-6203

Urn: uuid:221e19e4-b392-4d39-8968-8831c17e1c6f Item Description

Type: Article: post-print;

Language: en

Version: Publisher's versionSubjects: Orthopaedics Tiny URL: ora:4277

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Autor: Guillaume Mabilleau - institutionUniversity of Oxford facultyMedical Sciences Division - Orthopaedic Surgery - - - Afsie Sabokbar

Fuente: https://ora.ox.ac.uk/objects/uuid:221e19e4-b392-4d39-8968-8831c17e1c6f



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