{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:27:44Z","timestamp":1772893664895,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,7,25]],"date-time":"2006-07-25T00:00:00Z","timestamp":1153785600000},"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":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with leukocyte adhesion to and extravasation through vascular endothelium into synovial tissue. Recent evidence indicates that the thrombospondin 1 gene is up\u2010regulated in patients with RA. We have identified a region within the TSP\u20101 type 3 repeats that inhibits human neutrophil elastase (HNE) and binds to human neutrophils. The present study was undertaken to investigate the therapeutic benefit of this TSP\u20101\u2013derived peptide sequence and its effect on connective tissue growth factor (CTGF), a protein involved in fibrotic disorders and in neovascularization, which is a hallmark of RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP\u20101\u2013derived peptide were studied in the peptidoglycan\u2013polysaccharide animal model of erosive arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Peptide treatment prevented joint infiltration and inflammation and was associated with reduced circulating antigen levels of HNE and TSP\u20101. Additionally, CTGF was up\u2010regulated in this experimental model of RA. Treatment with the TSP\u20101\u2013derived peptide was associated with down\u2010regulation of the message and protein levels of CTGF. Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide\u2010treated group of animals was significantly less than that in the untreated group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results document a role for TSP\u20101 in regulating CTGF gene and protein expression in synovial tissue, suggesting a link with the disease course in this model of RA. This TSP\u20101\u2013derived synthetic peptide may represent an important template for drug development in RA and other inflammatory conditions associated with neutrophil activation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22021","type":"journal-article","created":{"date-parts":[[2006,7,25]],"date-time":"2006-07-25T23:17:14Z","timestamp":1153869434000},"page":"2415-2422","source":"Crossref","is-referenced-by-count":19,"title":["A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor"],"prefix":"10.1002","volume":"54","author":[{"given":"Joanne M.","family":"Manns","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey B.","family":"Uknis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario C.","family":"Rico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Agelan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Castaneda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel","family":"Arango","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary F.","family":"Barbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fayez F.","family":"Safadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven N.","family":"Popoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul A.","family":"DeLa Cadena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199707173370301"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.2947"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4480"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(96)00171-9"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2005.02.012"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003188200"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14632"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.114.6.1285"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.6.637"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.4.2958"},{"issue":"2","key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"ii60","DOI":"10.1136\/ard.62.suppl_2.ii60","article-title":"Angiogenesis as a target in rheumatoid arthritis","volume":"62","author":"Koch AE","year":"2003","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_6_13_2","doi-asserted-by":"crossref","first-page":"7139","DOI":"10.1016\/S0021-9258(18)53157-4","article-title":"Thrombospondin is a tight\u2010binding competitive inhibitor of neutrophil elastase","volume":"268","author":"Hogg PJ","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1067\/mlc.2000.109407"},{"key":"e_1_2_6_15_2","first-page":"G213","article-title":"Role of kallikrein\u2010kinin system in pathogenesis of bacterial cell wall\u2010induced inflammation","volume":"260","author":"DeLa Cadena RA","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200004)43:4<775::AID-ANR8>3.0.CO;2-7"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780401009"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500721200"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20746"},{"key":"e_1_2_6_20_2","first-page":"1","article-title":"Streptococcal cell\u2010wall\u2010induced arthritis in rats: an overview","volume":"10","author":"Wilder RL","year":"1988","journal-title":"Int J Tissue React"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.38.1.127-135.1982"},{"key":"e_1_2_6_22_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4049\/jimmunol.151.1.149","article-title":"Activated T\u2010cell adhesion to thrombospondin is mediated by the \u03b1 4 \u03b2 1 (VLA\u20104) and \u03b1 5 \u03b21 (VLA\u20105) integrins","volume":"151","author":"Yabkowitz R","year":"1993","journal-title":"J Immunol"}],"container-title":["Arthritis &amp; 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