Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin
Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bo...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , |
| التنسيق: | article |
| منشور في: |
2012
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/10346 http://dx.doi.org/10.1172/JCI60975 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.jci.org/articles/view/60975 |
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| _version_ | 1864513486563835904 |
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| author | Georgess, Dan |
| author2 | Harre, Ulrike Bang, Holger Bozec, Aline Axmann, Roland Ossipova, Elena |
| author2_role | author author author author author |
| author_facet | Georgess, Dan Harre, Ulrike Bang, Holger Bozec, Aline Axmann, Roland Ossipova, Elena |
| author_role | author |
| dc.creator.none.fl_str_mv | Georgess, Dan Harre, Ulrike Bang, Holger Bozec, Aline Axmann, Roland Ossipova, Elena |
| dc.date.none.fl_str_mv | 2012 2019-04-04T12:44:43Z 2019-04-04T12:44:43Z 2019-04-04 |
| dc.identifier.none.fl_str_mv | 1558-8238 http://hdl.handle.net/10725/10346 http://dx.doi.org/10.1172/JCI60975 Harre, U., Georgess, D., Bang, H., Bozec, A., Axmann, R., Ossipova, E., ... & Sarmay, G. (2012). Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. The Journal of clinical investigation, 122(5), 1791-1802. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.jci.org/articles/view/60975 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Journal of Clinical Investigation |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Autoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and bone-resorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_eeab579c6912dbeefe13ebdd809889e0 |
| identifier_str_mv | 1558-8238 Harre, U., Georgess, D., Bang, H., Bozec, A., Axmann, R., Ossipova, E., ... & Sarmay, G. (2012). Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. The Journal of clinical investigation, 122(5), 1791-1802. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/10346 |
| publishDate | 2012 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentinGeorgess, DanHarre, UlrikeBang, HolgerBozec, AlineAxmann, RolandOssipova, ElenaAutoimmunity is complicated by bone loss. In human rheumatoid arthritis (RA), the most severe inflammatory joint disease, autoantibodies against citrullinated proteins are among the strongest risk factors for bone destruction. We therefore hypothesized that these autoantibodies directly influence bone metabolism. Here, we found a strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption in RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination, and specific N-terminal citrullination of vimentin was induced during osteoclast differentiation. Affinity-purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to osteoclast surfaces, but also led to robust induction of osteoclastogenesis and bone-resorptive activity. Adoptive transfer of purified human MCV autoantibodies into mice induced osteopenia and increased osteoclastogenesis. This effect was based on the inducible release of TNF-α from osteoclast precursors and the subsequent increase of osteoclast precursor cell numbers with enhanced expression of activation and growth factor receptors. Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.PublishedN/A2019-04-04T12:44:43Z2019-04-04T12:44:43Z20122019-04-04Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1558-8238http://hdl.handle.net/10725/10346http://dx.doi.org/10.1172/JCI60975Harre, U., Georgess, D., Bang, H., Bozec, A., Axmann, R., Ossipova, E., ... & Sarmay, G. (2012). Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. The Journal of clinical investigation, 122(5), 1791-1802.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.jci.org/articles/view/60975enJournal of Clinical Investigationinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/103462021-03-19T10:45:18Z |
| spellingShingle | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin Georgess, Dan |
| status_str | publishedVersion |
| title | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| title_full | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| title_fullStr | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| title_full_unstemmed | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| title_short | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| title_sort | Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin |
| url | http://hdl.handle.net/10725/10346 http://dx.doi.org/10.1172/JCI60975 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.jci.org/articles/view/60975 |