{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:58:14Z","timestamp":1778083094686,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T00:00:00Z","timestamp":1369872000000},"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":[[2013,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We have shown that connective tissue growth factor (CTGF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to evaluate the effects of blockade of the CTGF pathway on the development of collagen\u2010induced arthritis (CIA) in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Arthritis was induced in DBA\/1J mice by immunization with a combination of type II collagen (CII) and Freund's complete adjuvant. We evaluated the development of arthritis in mice with CIA left untreated versus treated with neutralizing anti\u2010CTGF monoclonal antibody (mAb).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhibition of CTGF in mice treated with neutralizing anti\u2010CTGF mAb significantly ameliorated arthritis compared to the untreated mice with CIA. Serum levels of matrix metalloproteinase 3 were reduced by anti\u2010CTGF mAb treatment. Moreover, blockade of CTGF decreased interleukin\u201017 expression on purified CD4+ T lymphocytes. Although the expression of the retinoic acid receptor\u2013related orphan receptor \u03b3t gene was not suppressed by anti\u2010CTGF mAb treatment, that of interferon regulatory factor 4 (IRF\u20104) and I\u03baB\u03b6 (Nfkbiz), which are other important molecules for the differentiation of Th17 cells, was suppressed. In addition, blockade of CTGF inhibited pathologic proliferation of T lymphocytes in response to CII restimulation in vitro. Moreover, aberrant osteoclastogenesis in mice with CIA was restored by anti\u2010CTGF mAb treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that blockade of CTGF prevents the progression of arthritis in mice with CIA. Anti\u2010CTGF mAb treatment suppresses pathologic T cell function and restores aberrant osteoclastogenesis in mice with CIA. CTGF may become a new target for the treatment of RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37902","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T21:10:46Z","timestamp":1361567446000},"page":"1477-1486","source":"Crossref","is-referenced-by-count":40,"title":["Inhibition of Connective Tissue Growth Factor Ameliorates Disease in a Murine Model of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Kazuhisa","family":"Nozawa","sequence":"first","affiliation":[{"name":"Juntendo University School of Medicine, Tokyo, Japan, and Juntendo University Graduate School of Medicine Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Fujishiro","sequence":"additional","affiliation":[{"name":"Juntendo University Graduate School of Medicine Chiba 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