The anti-inflammatory effects of matrix metalloproteinase-3 on irreversible pulpitis of mature erupted teeth.

The anti-inflammatory effects of matrix metalloproteinase-3 on irreversible pulpitis of mature erupted teeth.
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DOI:
10.1371/journal.pone.0052523
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Nakashima M
Nakashima M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Eba H;Murasawa Y;Iohara K;Isogai Z;Nakamura H;Nakamura H;Nakashima M

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基质金属蛋白酶(MMPs)参与细胞外基质的降解和细胞行为的调节。这些蛋白酶也与组织修复和再生有关。我们的前期研究表明MMP-3在体外对内皮细胞的增殖和迁移具有刺激作用,并对这些细胞具有抗凋亡作用。此外,我们发现MMP-3增强了大鼠切牙牙髓损伤模型中丢失的牙髓组织的再生。然而,持续萌出的啮齿动物切牙表现出显着不同的牙髓组织与成熟萌出的牙齿。因此,我们使用犬不可逆牙髓炎模型进一步扩展了这些研究,以研究MMP-3的作用。本研究以成年犬的前磨牙为实验材料,切除牙冠,切断牙髓组织。切断的牙髓组织保持暴露24或72小时,分别诱导轻度或重度不可逆牙髓炎,然后封闭腔。在两种模型中,整个牙髓组织在第14天坏死。在该轻度牙髓炎模型中,观察到具有脉管系统和神经的牙髓组织的再生,直到用MMP-3封闭后14天,随后在再生的牙髓组织中形成细胞外基质,直到第28天。用MMP-3处理导致巨噬细胞和抗原呈递细胞的数量减少,并且在第3天显著抑制IL-6表达。MMP-3活性的抑制消除了这些抗炎作用。免疫荧光染色显示MMP-3可能通过多功能蛋白聚糖的降解参与了血清来源的透明质酸相关蛋白和透明质酸(SHAP-HA)复合物的修饰。这些结果表明,MMP-3可以作为一种抗炎剂,并建议MMP-3可能代表一个有用的治疗轻度不可逆性牙髓炎的治疗。
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.
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