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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19137064/?tool=EBI |
| _version_ | 1818931728839868416 |
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| author | Guillaume Mabilleau Afsie Sabokbar |
| author_facet | Guillaume Mabilleau Afsie Sabokbar |
| author_sort | Guillaume Mabilleau |
| collection | DOAJ |
| 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. |
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| format | Article |
| id | doaj.art-d8f089eeaf8448e3bc8fe2b9b0aa2d38 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T04:21:13Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d8f089eeaf8448e3bc8fe2b9b0aa2d382022-12-21T19:53:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0141e417310.1371/journal.pone.0004173Interleukin-32 promotes osteoclast differentiation but not osteoclast activation.Guillaume MabilleauAfsie Sabokbar<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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19137064/?tool=EBI |
| spellingShingle | Guillaume Mabilleau Afsie Sabokbar Interleukin-32 promotes osteoclast differentiation but not osteoclast activation. PLoS ONE |
| title | 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_short | Interleukin-32 promotes osteoclast differentiation but not osteoclast activation. |
| title_sort | interleukin 32 promotes osteoclast differentiation but not osteoclast activation |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19137064/?tool=EBI |
| work_keys_str_mv | AT guillaumemabilleau interleukin32promotesosteoclastdifferentiationbutnotosteoclastactivation AT afsiesabokbar interleukin32promotesosteoclastdifferentiationbutnotosteoclastactivation |