Matrix Metalloproteinase 3 Accelerates Wound Healing Following Dental Pulp Injury

Matrix metalloproteinases (MMPs) play critical roles in morphogenesis, angiogenesis, wound healing and tissue remodeling in physiology and pathology of inflammation and cancer. Vascular invasion is a prerequisite for reparative dentin formation during pulp wound healing. The mechanism of angiogenesis, however, still remains unclear. We hypothesized that the members of MMP family may play a role in pulp wound healing. Objectives: establish a rat pulp injury model and investigate the expression of MMPs during wound healing. Methods: Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to show MMPs expression after pulp injury. In situ hybridization and immunohistochemistry was used to show the localization of MMP-3 mRNA and protein in injured pulp in vivo. Proliferation, migration and anti-apoptotic assay were used to analysis the effect of MMP-3 on human umbilical vein endothelial cells (HUVECs) in vitro. Results: MMP-3 mRNA was upregulated at 24 hours after pulp injury, while expression of MMP-1, MMP-2, MMP-9 and MMP-14 was not changed. In situ hybridization and immunohistochemistry showed that MMP-3 mRNA and protein were localized in endothelial cells and/or endothelial progenitor cells in injured pulp in vivo. MMP-3 demonstrated mitogenic, chemotactic and anti-apoptotic activities on human umbilical vein endothelial cells (HUVECs) in vitro. Furthermore, the topical application of MMP-3 protein in vivo on the rat injured pulp tissue induced angiogenesis and reparative dentin formation significantly higher compared with control at 24 hours and 72 hours after treatment, respectively. Conclusion: These results provide suggestive evidence that MMP-3 released from endothelial cells and/or endothelial progenitor cells in injured pulp plays critical roles in angiogenesis and has potential therapeutic implication in pulp wound healing. (support: Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan, Aichigakuin University High-Tech Research Center, Japan and Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan)