Metalloproteases and CCN2/CTGF in dentin–pulp complex repair

Abstract Background Metalloproteases are widely regarded as catalytic enzymes involved in extracellular matrix remodeling in the dental pulp. However, cells internalize several metalloproteases, including matrix metalloprotease (MMP)-2, MMP-3, MMP-9, and MMP-13. Recently, MMP-3 was shown to mediate dental pulp healing as an anti-inflammatory and regenerative factor. Highlight Our previous study showed that MMP-3 stimulates cell migration. This occurs via CCN family member 2/connective tissue growth factor (CCN2/CTGF) expression and secretion in human dental pulp cells, a process dependent on dynamin-related endocytosis and independent of protease activity. Furthermore, we recently revealed that bone morphogenetic protein (BMP)-1, a member of the astacin metalloprotease family, plays a role in reparative dentinogenesis via CCN2/CTGF expression. During this process, the protease activity of BMP-1 is not necessary for CCN2/CTGF expression. These results suggest a new role for metalloproteases in activating signaling cascades required for CCN2/CTGF expression in the dental pulp. Conclusion In this review, we summarize novel roles for metalloproteases, particularly MMP-3 and BMP-1, in dentin–pulp complex repair, with particular emphasis on the effects of CCN2/CTGF expression during regulation of cell migration and tertiary dentinogenesis.