{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:56:46Z","timestamp":1772161006673,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T00:00:00Z","timestamp":1361750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate how tumor necrosis factor (TNF)\u2013inhibiting therapy affects bone destruction and inflammation in a TNF\u2010driven mouse model of rheumatoid arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In order to evaluate the influence of TNF on osteoclastogenesis in vitro, different concentrations of TNF were added to spleen cell\u2013derived monocytes in the absence or presence of different concentrations of RANKL. In addition, the effects of TNF inhibition on osteoclast precursors as well as local bone destruction in vivo were assessed by treating TNF\u2010transgenic mice with different doses of adalimumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TNF stimulated osteoclastogenesis mainly by increasing the number of osteoclast precursor cells in vitro. This TNF effect was independent of the presence of RANKL. In the hTNF\u2010transgenic mouse model of destructive arthritis, low\u2010dose TNF\u2010inhibiting therapy with adalimumab had no effect on synovial inflammation but significantly inhibited local bone destruction and the generation of osteoclasts. This inhibition was accompanied by a reduction in the number of c\u2010Fms\u2013positive osteoclast precursor cells in the bone marrow and a reduction of the osteoclast precursor pools in the blood and inflamed synovial membrane of hTNF\u2010transgenic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Low\u2010dose TNF\u2010inhibiting therapy significantly reduces bone erosions by reducing the number of circulating and joint\u2010invading osteoclast precursors. This effect is uncoupled from its antiinflammatory action.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37797","type":"journal-article","created":{"date-parts":[[2012,12,28]],"date-time":"2012-12-28T17:04:36Z","timestamp":1356714276000},"page":"608-617","source":"Crossref","is-referenced-by-count":49,"title":["Tumor necrosis factor\u2013inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor\u2013driven model of rheumatoid arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Nikolaus 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