Studies on the mechanism of actions of a cartilage-derived pleiotrophic growth factor, ecogenin/CTGF - Molecular cloning of its receptors and mechanism of inter- and intra signal transduction -

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1) Specific receptors for ecogenin/CTGF were found on chondrocytes, osteoblasts and vascular endothelial cells. Its molecular weight was about 240 kDa.2) Specific binding of radiolabeled ecogenin/CTGF for chondrocytes decreased as the cells differentiated.3) In chondrocyte culture system, ecogenin/CTGF bound cell surface heparan sulfate proteoglycans after secreted and was then released, suggesting that it is a matricrine factor.4) Ecogenin/CTGF stimulated phosphorylation of ERK and p38MAPK in chondrocytes. Using specific inhibitors, we found that ecogenin/CTGF promoted the proliferation and differentiation of chondrocytes through ERK and p38MAPK pathways, respectively.5) Two binding proteins for ecogenin/CTGF were purified from human chondrocytic cell line HCS-2/8. The one was 42 kDa protein of which N-terminal amino acid sequence corresponded to that of γ-actin and the other was 50 kDa protein of which N-terminal amino acid sequence corresponded to that of cytokeratin.6) When ecogenin/CTGF was overexpressed in Cos-7 cells, it localized around centrosome. C-terminal fragment was also found in cells.These findings suggest that ecogenin/CTGF not only acts as a paracrine and matricrine factor through its specfic receptors but also functions through an alternative intracellular pathway.