Enhanced wound healing by matrix metalloproteinase-3 after dental pulp amputation

Objectives: Matrix metalloproteinases (MMPs) play critical roles in morphogenesis, angiogenesis, wound healing and tissue remodeling in the physiology and pathology of inflammation and cancer. When the pulp is damaged or exposed, pulp cells have the potential to differentiate into dentin-forming odontoblasts. However, the mechanism of angiogenesis during pulp wound healing still remains unclear. We hypothesized that a member of the matrix metalloproteinases, MMP-3, may play a role in pulp wound healing. Methods: Dental pulp tissues were isolated immediately and 12, 24, 48 and 72 hours after injury and real-time RT-PCR of MMP-3 was performed. Immunohistochemical analysis of MMP-3 was performed 24 and 72 hours after injury. The proliferative, migrative and anti-apoptotic effects of MMP-3 were examined in vitro. MMP-3 was applied to the amputated pulp, and newly formed blood vessels at 24 hours were quantitatively analyzed by staining with BS-1 lectin. Reparative dentin formation was compared with a PBS control at 72 hours after treatment. Results: MMP-3 mRNA was upregulated at 24 hours after pulp injury. MMP-3 protein was localized in endothelial and/or endothelial progenitor cells in injured pulp in vivo. MMP-3 showed mitogenic, chemotactic and anti-apoptotic effects on human umbilical vein endothelial cells (HUVECs) in vitro. Furthermore, the application of MMP-3 protein to the amputated pulp enhanced angiogenesis and reparative dentin formation in vivo. Conclusion: These results suggest that MMP-3 released from endothelial and/or endothelial progenitor cells in injured pulp might play critical roles in angiogenesis and pulp wound healing.