{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:08:30Z","timestamp":1791590910092,"version":"4.3.4"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,7,10]]},"abstract":"<jats:p>\n                    Blocking TNF effectively inhibits inflammation and structural damage in human rheumatoid arthritis (RA). However, so far it is unclear whether the effect of TNF is a direct one or indirect on up-regulation of other mediators. IL-1 may be one of these candidates because it has a central role in animal models of arthritis, and inhibition of IL-1 is used as a therapy of human RA. We removed the effects of IL-1 from a TNF-mediated inflammatory joint disease by crossing IL-1\u03b1 and \u03b2-deficient mice (IL-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) with arthritic human TNF-transgenic (hTNFtg) mice. Development of synovial inflammation was almost unaffected on IL-1 deficiency, but bone erosion and osteoclast formation were significantly reduced in IL-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    hTNFtg mice, compared with hTNFtg mice based on an intrinsic differentiation defect of IL-1-deficient monocytes. Most dramatically, however, cartilage damage was absent in IL-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    hTNFtg mice. Chimera studies revealed that protection of cartilage is based on the loss of IL-1 on hematopoietic, but not mesenchymal, cells, leading to decreased expression of ADAMTS-5 and MMP-3. These data show that TNF-mediated cartilage damage is completely and TNF-mediated bone damage is partially dependent on IL-1, suggesting that IL-1 is a crucial mediator for inflammatory cartilage and bone degradation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0610812104","type":"journal-article","created":{"date-parts":[[2007,7,3]],"date-time":"2007-07-03T20:54:44Z","timestamp":1183496084000},"page":"11742-11747","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":268,"title":["TNF-induced structural joint damage is mediated by IL-1"],"prefix":"10.1073","volume":"104","author":[{"given":"Jochen","family":"Zwerina","sequence":"first","affiliation":[{"name":"*Department of Internal Medicine III, Medical University of Vienna, A-1090 Vienna, Austria;"},{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, 91054 Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Redlich","sequence":"additional","affiliation":[{"name":"*Department of Internal Medicine III, Medical University of Vienna, A-1090 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Polzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, 91054 Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Joosten","sequence":"additional","affiliation":[{"name":"Rheumatology Research and Advanced Therapeutics and Departments of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, 7500 AE, Enschede, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kr\u00f6nke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3, University of Erlangen-Nuremberg, 91054 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