title: The anti-inflammatory effects of matrix metalloproteinase-3 on irreversible pulpitis of mature erupted teeth.
abstract: Matrix metalloproteinases (MMPs) are involved in extracellular matrix degradation and the modulation of cell behavior. These proteinases have also been implicated in tissue repair and regeneration. Our previous studies have demonstrated that 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. In addition, we found that MMP-3 enhanced the regeneration of lost pulp tissue in a rat incisor pulp injury model. 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.
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Eba
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murasawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Iohara
authors.forename: Zenzo
authors.initials: Z
authors.lastname: Isogai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D003782:Dental Pulp / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000494:pharmacology / Q000627:therapeutic use*; D021381:Protein Transport / Q000187:drug effects; D011671:Pulpitis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D013997:Time Factors; D014078:Tooth Eruption / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D053675:Versicans / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000510:Alpha-Globulins; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006820:Hyaluronic Acid; D015850:Interleukin-6; D019278:Matrix Metalloproteinase 3; D014409:Tumor Necrosis Factor-alpha; D053675:Versicans; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C011877:inter-alpha-inhibitor