CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell adhesion of chondrocytes through integrin α5β1

Abstract

Searching for CCN family protein 2/connective tissue growth factor (CCN2/CTGF) interactive proteins by yeast-twohybrid screening, we identified fibronectin 1 gene product as a major binding partner of CCN2/CTGF in the chondrosarcomaderived chondrocytic cell line HCS-2/8. Only the CT domain of CCN2/CTGF bound directly to fibronectin (FN). CCN2/ CTGF and its CT domain enhanced the adhesion of HCS-2/8 cells to FN in a dose-dependent manner. The CCN2/CTGFenhancing effect on cell adhesion to FN was abolished by a blocking antibody against a5b1 integrin (a5b1), but not by one against anti-avb3 integrin. These findings suggest for the first time that CCN2/CTGF enhances chondrocyte adhesion to FN through direct interaction of its C-terminal CT domain with FN, and that a5b1 is involved in this adhesion.

Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells

“…Antisense oligonucleotides to the integrin receptor subunit ␣5 decreased FN fragment-mediated cartilage chondrolysis (49). Chondrosarcoma-derived chondrocytic cell adhesion to FN was abolished by a blocking antibody against ␣5␤1 integrin, but not by one against anti-␣v␤3 integrin, suggesting the specificity of this integrin in mediating many FN functions (50).…”

CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes

“…It has also been shown that CCN2 binds several types of integrins in fibroblasts and endothelial cells (Lau and Lam 1999;Brigstock 2003;Babic et al 1999;Leu et al 2003;Chen et al 2004;Hoshijima et al 2006;Tong and Brigstock 2006;Brigstock 2005, 2006). Therefore, we examined levels of expression of various integrin subunits in chondrocytes by quantitative real-time PCR analysis.…”

“…Given that multiple members of the CCN family have essential functions in chondrogenesis, understanding the mechanisms by which these proteins function is an important issue. CCN2 functions as a ligand for integrins in vitro (Lau and Lam 1999;Babic et al 1999;Leu et al 2003;Chen et al 2004;Gao and Brigstock 2004;Hoshijima et al 2006;Tong and Brigstock 2006). Integrins play a fundamental role in chondrocyte survival, proliferation and differentiation (Hynes 2002;Loeser 2002).…”

Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

“…This mosaic structure has resulted in CTGF and other CCN proteins being implicated both directly and indirectly in a vast array of biological processes and has made it difficult to predict the function of CTGF in any given biological context (Holbourn, Acharya et al 2008;Chen and Lau 2009). However, there is a growing body of evidence that CTGF acts to connect cells to the microenvironment by providing adhesive signals (Gao and Brigstock 2006;Hoshijima, Hattori et al 2006) as well as modulating the availability and function of soluble growth factors A c c e p t e d M a n u s c r i p t 4 (Abreu, Ketpura et al 2002;Hashimoto, Inoki et al 2002;Nguyen, Roestenberg et al 2008). Thus, the tissue context within which CTGF is expressed is likely to play a key role in determining its biological function in any given microenvironment.…”