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The mechanisms by which CCN2\/CTGF contributes to fibrosis are not well understood. Previous studies suggest that CTGF exerts some of its biological effects at least in part by integrin binding, though this mechanism has not been previously shown to contribute to fibrosis. Utilizing full length CCN2\/CTGF, CCN2\/CTGF fragments, and integrin neutralizing antibodies, we provide evidence that the effects of CCN2\/CTGF to stimulate extracellular matrix deposition by gingival fibroblasts are mediated by the C\u2010terminal half of CCN2\/CTGF, and by \u03b16 and \u03b21 integrins. In addition, a synthetic peptide corresponding to a region of CCN2\/CTGF domain 3 that binds \u03b16\u03b21 inhibits the collagen\u2010deposition assay. These studies employed a new and relatively rapid assay for CCN2\/CTGF\u2010stimulated collagen deposition based on Sirius Red staining of cell layers. Data obtained support a pathway in which CCN2\/CTGF could bind to \u03b16\u03b21 integrin and stimulate collagen deposition. These findings provide new experimental methodologies applicable to uncovering the mechanism and signal transduction pathways of CCN2\/CTGF\u2010mediated collagen deposition, and may provide insights into potential therapeutic strategies to treat gingival fibrosis and other fibrotic conditions. J. Cell. Biochem. 98: 409\u2013420, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20810","type":"journal-article","created":{"date-parts":[[2006,1,26]],"date-time":"2006-01-26T21:46:36Z","timestamp":1138311996000},"page":"409-420","source":"Crossref","is-referenced-by-count":93,"title":["CCN2, connective tissue growth factor, stimulates collagen deposition by gingival fibroblasts via module 3 and \u03b16\u2010 and \u03b21 integrins"],"prefix":"10.1002","volume":"98","author":[{"given":"Edwin C.K.","family":"Heng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Samuel A.","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip 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