{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:41:56Z","timestamp":1789123316783,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korean government, Ministry of Science, ICT, and Future Planning","award":["2008-0062279"],"award-info":[{"award-number":["2008-0062279"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Insulin\u2010like growth factor binding protein 3 (IGFBP\u20103) is known to interfere with the NF\u2010\u03baB signaling pathway, and it effectively promotes apoptosis in tumor cells by a variety of mechanisms. NF\u2010\u03baB activation and apoptosis resistance of fibroblast\u2010like synoviocytes (FLS) play pivotal roles in rheumatoid arthritis (RA). This study was undertaken to evaluate whether IGFBP\u20103 has antiarthritic effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To deliver IGFBP\u20103, we used an adenovirus containing IGFBP\u20103 complementary DNA (AdIGFBP\u20103) or IGFBP\u20103 mutant that is devoid of IGF binding affinity but retains IGFBP\u20103 receptor binding ability (AdmtIGFBP\u20103). The regulatory roles of IGFBP\u20103 in inflammation and bone destruction were investigated in mice with collagen\u2010induced arthritis (CIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IGFBP\u20103 levels were significantly higher in patients with RA than in those with osteoarthritis (OA) and were notably higher in patients with active RA. AdIGFBP\u20103 suppressed NF\u2010\u03baB activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor \u03b1 (TNF\u03b1) in RA FLS. AdIGFBP\u20103 sensitized RA FLS to TNF\u03b1\u2010induced apoptosis in vitro and also significantly increased apoptosis in an in vivo model of Matrigel implants engrafted into immunodeficient mice. AdIGFBP\u20103\u2013injected mice with CIA had attenuated arthritis severity and reduced radiologic and pathologic abnormalities. Moreover, AdIGFBP\u20103 down\u2010regulated local and systemic levels of NF\u2010\u03baB\u2013targeted proinflammatory cytokines. Of note, RA FLS and mice with CIA treated with AdmtIGFBP\u20103 exhibited similar effects as those treated with AdIGFBP\u20103.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that both the inflammatory response and bone destruction are reduced with blockage of NF\u2010\u03baB activation and induction of apoptosis in RA FLS by IGFBP\u20103. Therefore, IGFBP\u20103 may have therapeutic potential in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38303","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T14:47:17Z","timestamp":1386686837000},"page":"863-873","source":"Crossref","is-referenced-by-count":56,"title":["Regulation of Apoptosis and Inflammatory Responses by Insulin\u2010like Growth Factor Binding Protein 3 in Fibroblast\u2010like Synoviocytes and Experimental Animal Models of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Hwa\u2010Suk","family":"Lee","sequence":"first","affiliation":[{"name":"Chonbuk National University Medical School Jeonju, Jeonbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Ji","family":"Woo","sequence":"additional","affiliation":[{"name":"Chonbuk National University Medical School Jeonju, Jeonbuk Republic of 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