MMP-7 and TIMP-1, New Targets in Predicting Poor Wound Healing in Apical Periodontitis

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• 作者：Ariadne Letra ; DDS ; MS ; PhD^&lowast ; ; Ghazaleh Ghaneh ; DDS^&lowast ; ; Min Zhao ; PhD^&lowast ; ; Herbert Ray Jr. ; DMD^&dagger ; ; Carolina Favaro Francisconi ; DDS^&Dagger ; ; Gustavo Pompermaier Garlet ; DDS ; MS ; PhD^&Dagger ; ; Renato Menezes Silva ; DDS ; MS ; PhD^&lowast ; ; ^{Renato.M.Silva@uth.tmc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Apical periodontitis ; gene expression ; matrix metalloproteinase ; tissue inhibitor of metalloproteinase
• 刊名：Journal of Endodontics
• 出版年：2013
• 出版时间：September 2013
• 年：2013
• 卷：39
• 期：9
• 页码：1141-1146
• 全文大小：1287 K

文摘

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) are strongly associated with tissue destruction because of inflammation. In this study, we investigated the expression of MMPs and TIMPs messenger RNA and protein levels in apical periodontitis lesions.

Methods

Tissue samples from patients presenting clinical signs of chronic apical abscess (CAA) or asymptomatic apical periodontitis (AAP) were collected postoperatively and used for gene expression analysis of MMP-2, -3, -7, -9, -14, -16, and -25; TIMP-1; and TIMP-2 in real-time polymerase chain reaction. Immunohistochemistry was also performed to detect the expression of MMP-7 and TIMP-1 proteins. Lastly, U-937 cells were induced to terminal differentiation into macrophages, infected with purified Escherichia coli lipopolysaccharide, and assessed for the expression of MMP-7 and TIMP-1 using immunocytochemistry and confocal microscopy.

Results

Significantly higher messenger RNA levels were found for all genes in AAP and CAA samples when compared with healthy control samples (P < .001). AAP cases exhibited significantly higher TIMP-1 when compared with CAA cases, whereas CAA cases showed higher MMP-2, MMP-7, and MMP-9 messenger RNA levels (P < .05). We also detected positive the expression of MMP-7 and TIMP-1 proteins in the tissue samples. The expression of both MMP-7 and TIMP-1 were increased in lipopolysaccharide-stimulated cells compared with nonstimulated cells and appear to colocalize in the Golgi apparatus.

Conclusions

MMPs appear to have an influential role in CAA cases in which ongoing tissue destruction is observed. TIMPs are preferentially associated with AAP, perhaps as a subsequent defense mechanism against excessive destruction. Taken together, our findings implicate MMP and TIMP molecules in the dynamics of inflammatory periapical lesion development.