Metalloproteases and CCN2/CTGF in dentin–pulp complex repair

BackgroundMetalloproteases 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.HighlightOur 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.ConclusionIn 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.