MMP-3 provokes CTGF/CCN2 production independently of protease activity and dependently on dynamin-related endocytosis, which contributes to human dental pulp cell migration

Matrix metalloproteinase‐3 (MMP‐3) expression is promoted after pulpotomy, and application of MMP‐3 to dental pulp after pulpotomy accelerates angiogenesis and hard tissue formation. However, the mechanism by which MMP‐3 promotes dental pulp wound healing is still unclear. Connective tissue growth factor/CCN family 2 (CTGF/CCN2), a protein belonging to the CCN family, is considered to participate in wound healing, angiogenesis, and cell migration. In this study, we examined the involvement of CTGF/CCN2 in MMP‐3‐induced cell migration in human dental pulp (fibroblast‐like) cells. In human dental pulp cells, MMP‐3 promoted cell migration, but this effect was clearly blocked in the presence of anti‐CTGF/CCN2 antibody. MMP‐3 provoked mRNA and protein expression and secretion of CTGF/CCN2 in a concentration‐ and time‐dependent manner. The MMP‐3 inhibitor NNGH failed to suppress MMP‐3‐induced CTGF/CCN2 protein expression. The potent dynamin inhibitor dynasore clearly inhibited MMP‐3‐induced CTGF/CCN2 expression. These results strongly suggest that MMP‐3 induces CTGF/CCN2 production independently of the protease activity of MMP‐3 and dependently on dynamin‐related endocytosis, which is involved in cell migration in human dental pulp cells. J. Cell. Biochem. 113: 1348–1358, 2012. © 2011 Wiley Periodicals, Inc.