Anti-Inflammatory Effects of Matrix Metalloproteinase-3 on Irreversible Pulpitis of Mature Erupted Teeth

The entire pulp of a tooth affected by irreversible pulpitis should be removed, regardless of the amount of remaining normal pulp tissue. However, long-term studies have shown that the rate of tooth loss is higher for endodontically treated teeth compared to nontreated teeth, due to fracture, secondary caries and complex restoration-associated problems (1). This has been one of the central challenges in dentistry, and thus the improvement of antimicrobial agents and restorative materials and the diagnosis of pulp vitality to facilitate the control of infection are great interest. The treatment of irreversible pulpitis aims to restore the original architecture and biological function of the infected pulp tissue by facilitating repair or by allowing for tissue regeneration. Our previous studies have demonstrated that Matrix metalloproteinase-3 (MMP-3) elicits stimulatory effects on the proliferation and the migration of endothelial cells as well as anti-apoptotic effects on these cells in vitro (2). MMPs are involved in extracellular matrix degradation and the modulation of cell behavior. These proteinases have also been implicated in tissue repair and regeneration. In addition, we found that MMP-3 enhanced the regeneration of lost pulp tissue in a rat incisor pulp injury model (2). However, continuously erupting rodent incisors exhibit significantly different pulp organization compared with mature erupted teeth. Therefore, we have further extended these studies using a canine irreversible pulpitis model to investigate the effects of MMP-3. In this study, the crowns of the canine mature premolars were removed and the pulp tissues were amputated. The amputated pulp tissues remained exposed for 24 or 72 hours to induce mild or severe irreversible pulpitis, respectively, followed by sealing of the cavities. In both models, the whole pulp tissues became necrotic by day 14. In this mild pulpitis model, the regeneration of pulp tissue with vasculature and nerves was observed until 14 days after sealing with MMP-3, followed by extracellular matrix formation in the regenerated pulp tissues until day 28. The treatment with MMP-3 resulted in a decrease in the number of macrophage and antigen-presenting cells and a significant inhibition of IL-6 expression on day 3. The inhibition of MMP-3 activity abolished these anti-inflammatory effects. Immunofluorescence staining demonstrated that MMP-3 was involved in the modification of serum-derived hyaluronan associated proteins and hyaluronan (SHAP-HA) complexes possibly through the degradation of versican. These results demonstrate that MMP-3 can act as an anti-inflammatory agent and suggest that MMP-3 might represent a useful therapy for the treatment of mild irreversible pulpitis.

References

1.           Caplan DJ, Cai J, Yin G, White BA. Root canal filled versus non-root canal filled teeth: a retrospective comparison of survival times. J Public Health Dent. 2005;65(2):90-6.

2.           Zheng L, Amano K, Iohara K, Ito M, Imabayashi K, Into T, et al. Matrix metalloproteinase-3 accelerates wound healing following dental pulp injury. Am J Pathol. 2009;175(5):1905-14.