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Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases during Apical Periodontitis Development

Published:April 22, 2021DOI:https://doi.org/10.1016/j.joen.2021.04.005

      Abstract

      Introduction

      Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice.

      Methods

      AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis.

      Results

      The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods.

      Conclusions

      MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP.

      Key Words

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      References

        • Nair P.N.
        Pathogenesis of apical periodontitis and the causes of endodontic failures.
        Crit Rev Oral Biol M. 2004; 15: 348-381
        • Nagase H.
        • Woessner Jr., J.F.
        Matrix metalloproteinases.
        J Biol Chem. 1999; 274: 21491-21494
        • Tsuji M.
        • Yamasaki M.
        • Amano K.
        • et al.
        Histochemical localization of neutral proteases released during development of rat periradicular lesion.
        Arch Oral Biol. 2009; 54: 1128-1135
        • Curran S.
        • Murray G.I.
        Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis.
        Eur J Cancer. 2000; 36: 1621-1630
        • Butler G.S.
        • Overall C.M.
        Updated biological roles for matrix metalloproteinases and new "intracellular" substrates revealed by degradomics.
        Biochemistry. 2009; 48: 10830-10845
        • Shin S.J.
        • Lee J.I.
        • Baek S.H.
        • Lim S.S.
        Tissue levels of matrix metalloproteinases in pulps and periapical lesions.
        J Endod. 2002; 28: 313-315
        • Wahlgren J.
        • Salo T.
        • Teronen O.
        • et al.
        Matrix metalloproteinase-8 (MMP-8) in pulpal and periapical inflammation and periapical root-canal exudates.
        Int Endod J. 2002; 35: 897-904
        • Accorsi-Mendonca T.
        • Silva E.J.
        • Marcaccini A.M.
        • et al.
        Evaluation of gelatinases, tissue inhibitor of matrix metalloproteinase-2, and myeloperoxidase protein in healthy and inflamed human dental pulp tissue.
        J Endod. 2013; 39: 879-882
        • Belmar M.J.
        • Pabst C.
        • Martinez B.
        • Hernandez M.
        Gelatinolytic activity in gingival crevicular fluid from teeth with periapical lesions.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 105: 801-806
        • Corotti M.V.
        • Zambuzzi W.F.
        • Paiva K.B.
        • et al.
        Immunolocalization of matrix metalloproteinases-2 and -9 during apical periodontitis development.
        Arch Oral Biol. 2009; 54: 764-771
        • Matsui H.
        • Yamasaki M.
        • Nakata K.
        • et al.
        Expression of MMP-8 and MMP-13 in the development of periradicular lesions.
        Int Endod J. 2011; 44: 739-745
        • Andonovska B.
        • Dimova C.
        • Panov S.
        Matrix metalloproteinases (MMP-1, -8, -13) in chronic periapical lesions.
        Vojnosanit Pregl. 2008; 65: 882-886
        • Gomis-Ruth F.X.
        • Maskos K.
        • Betz M.
        • et al.
        Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1.
        Nature. 1997; 389: 77-81
        • Fernandez-Catalan C.
        • Bode W.
        • Huber R.
        • et al.
        Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor.
        EMBO J. 1998; 17: 5238-5248
        • Gomez D.E.
        • Alonso D.F.
        • Yoshiji H.
        • Thorgeirsson U.P.
        Tissue inhibitors of metalloproteinases: structure, regulation and biological functions.
        Eur J Cell Biol. 1997; 74: 111-122
        • Chang C.
        • Werb Z.
        The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis.
        Trends Cell Biol. 2001; 11: S37-S43
        • Nagase H.
        • Visse R.
        • Murphy G.
        Structure and function of matrix metalloproteinases and TIMPs.
        Cardiovasc Res. 2006; 69: 562-573
        • Hadziabdic N.
        • Kurtovic-Kozaric A.
        • Pojskic N.
        • et al.
        Gene-expression analysis of matrix metalloproteinases 1 and 2 and their tissue inhibitors in chronic periapical inflammatory lesions.
        J Oral Pathol Med. 2016; 45: 224-230
        • Letra A.
        • Ghaneh G.
        • Zhao M.
        • et al.
        MMP-7 and TIMP-1, new targets in predicting poor wound healing in apical periodontitis.
        J Endod. 2013; 39: 1141-1146
        • Martinho F.C.
        • Teixeira F.F.
        • Cardoso F.G.
        • et al.
        Clinical investigation of matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase complexes and their networks in apical periodontitis.
        J Endod. 2016; 42: 1082-1088
        • Goldman E.
        • Reich E.
        • Abramovitz I.
        • Klutstein M.
        Inducing apical periodontitis in mice.
        J Vis Exp. 2019; 6: 150
        • Schmittgen T.D.
        • Livak K.J.
        Analyzing real-time PCR data by the comparative C(T) method.
        Nat Protoc. 2008; 3: 1101-1108
        • Jain A.
        • Bahuguna R.
        Role of matrix metalloproteinases in dental caries, pulp and periapical inflammation: an overview.
        J Oral Biol Craniofac Res. 2015; 5: 212-218
        • Lin S.K.
        • Chiang C.P.
        • Hong C.Y.
        • et al.
        Immunolocalization of interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in radicular cysts.
        J Oral Pathol Med. 1997; 26: 458-463
        • Tsubota M.
        • Sasano Y.
        • Takahashi I.
        • et al.
        Expression of MMP-8 and MMP-13 mRNAs in rat periodontium during tooth eruption.
        J Dent Res. 2002; 81: 673-678
        • Martinho F.C.
        • Chiesa W.M.
        • Leite F.R.
        • et al.
        Antigenic activity of bacterial endodontic contents from primary root canal infection with periapical lesions against macrophage in the release of interleukin-1beta and tumor necrosis factor alpha.
        J Endod. 2010; 36: 1467-1474
        • Lu B.
        • Zhang J.
        • Huang X.
        • et al.
        Expression of interleukin-1beta and matrix metalloproteinase-8 in cytolytic and noncytolytic enterococcus faecalis-induced persistent apical periodontitis: a comparative study in the rat.
        J Endod. 2015; 41: 1288-1293
        • Paula-Silva F.W.
        • da Silva L.A.
        • Kapila Y.L.
        Matrix metalloproteinase expression in teeth with apical periodontitis is differentially modulated by the modality of root canal treatment.
        J Endod. 2010; 36: 231-237
        • Patterson M.L.
        • Atkinson S.J.
        • Knauper V.
        • Murphy G.
        Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain.
        FEBS Lett. 2001; 503: 158-162
        • Aimes R.T.
        • Quigley J.P.
        Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments.
        J Biol Chem. 1995; 270: 5872-5876
        • Price S.J.
        • Greaves D.R.
        • Watkins H.
        Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation.
        J Biol Chem. 2001; 276: 7549-7558
        • Delaisse J.M.
        • Engsig M.T.
        • Everts V.
        • et al.
        Proteinases in bone resorption: obvious and less obvious roles.
        Clin Chim Acta. 2000; 291: 223-234
        • Pereira Faustino I.S.
        • Azevedo R.S.
        • Takahama Jr., A.
        Metalloproteinases 2 and 9 immunoexpression in periapical lesions from primary endodontic infection: possible relationship with the histopathological diagnosis and the presence of pain.
        J Endod. 2016; 42: 547-551
        • Buzoglu H.D.
        • Unal H.
        • Ulger C.
        • et al.
        The zymographic evaluation of gelatinase (MMP-2 and -9) levels in acute and chronic periapical abscesses.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009; 108: e121-e126
        • Ahmed G.M.
        • El-Baz A.A.
        • Hashem A.A.
        • Shalaan A.K.
        Expression levels of matrix metalloproteinase-9 and gram-negative bacteria in symptomatic and asymptomatic periapical lesions.
        J Endod. 2013; 39: 444-448
        • McMillan S.J.
        • Kearley J.
        • Campbell J.D.
        • et al.
        Matrix metalloproteinase-9 deficiency results in enhanced allergen-induced airway inflammation.
        J Immunol. 2004; 172: 2586-2594
        • Wan C.
        • Yuan G.
        • Yang J.
        • et al.
        MMP9 deficiency increased the size of experimentally induced apical periodontitis.
        J Endod. 2014; 40: 658-664
        • Zhang H.
        • Liu L.
        • Jiang C.
        • et al.
        MMP9 protects against LPS-induced inflammation in osteoblasts.
        Innate Immun. 2020; 26: 259-269
        • Accorsi-Mendonca T.
        • Paiva K.B.
        • Zambuzzi W.F.
        • et al.
        Expression of matrix metalloproteinases-2 and -9 and RECK during alveolar bone regeneration in rat.
        J Mol Histol. 2008; 39: 201-208