Advertisement
Basic Research| Volume 36, ISSUE 2, P231-237, February 2010

Matrix Metalloproteinase Expression in Teeth with Apical Periodontitis Is Differentially Modulated by the Modality of Root Canal Treatment

      Abstract

      Introduction

      The objective of this study was to investigate the expression of matrix metalloproteinases (MMPs) in apical periodontitis and during the periapical healing phase after root canal treatment.

      Methods

      Apical periodontitis was induced in dog teeth, and root canal treatment was performed in a single visit or by using an additional calcium hydroxide root canal dressing. One hundred eighty days after treatment the presence of inflammation was examined, and tissues were stained to detect bacteria. Bacterial status was correlated to the degree of tissue organization, and to further investigate molecules involved in this process, tissues were stained for MMP-1, MMP-2, MMP-8, and MMP-9. Data were analyzed by using one-way analysis of variance followed by Tukey test or Kruskal-Wallis followed by Dunn test.

      Results

      Teeth with apical periodontitis that had root canal therapy performed in a single visit presented an intense inflammatory cell infiltrate. Periapical tissue was extremely disorganized, and this was correlated with the presence of bacteria. Higher MMP expression was evident, similar to teeth with untreated apical periodontitis. In contrast, teeth with apical periodontitis submitted to root canal treatment with calcium hydroxide presented a lower inflammatory cell infiltrate. This group had moderately organized connective tissue, lower prevalence of bacteria, and lower number of MMP-positive cells, similar to healthy teeth submitted to treatment.

      Conclusions

      Teeth treated with calcium hydroxide root canal dressing exhibited a lower percentage of bacterial contamination, a lower MMP expression, and a more organized extracellular matrix, unlike those treated in a single visit. This suggests that calcium hydroxide might be beneficial in tissue repair processes.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Endodontics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kawashima N.
        • Stashenko P.
        Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation.
        Arch Oral Biol. 1999; 44: 55-66
        • Martón I.J.
        • Kiss C.
        Protective and destructive immune reactions in apical periodontitis.
        Oral Microbiol Immunol. 2000; 15: 139-150
        • Liapatas S.
        • Nakou M.
        • Rontogianni D.
        Inflammatory infiltrate of chronic periradicular lesions: an immunohistochemical study.
        Int Endod J. 2003; 36: 464-471
        • Kabak S.L.
        • Kabak Y.S.
        • Anischenko S.L.
        Light microscopic study of periapical lesions associated with asymptomatic apical periodontitis.
        Ann Anat. 2005; 187: 185-194
        • Stashenko P.
        • Yu S.M.
        T helper and T suppressor cell reversal during the development of induced rat periapical lesions.
        J Dent Res. 1989; 65: 830-834
        • Wang C.Y.
        • Stashenko P.
        The role of interleukin-1α in the pathogenesis of periapical bone destruction in a rat model system.
        Oral Microbiol Immunol. 1993; 8: 50-56
        • Yamasaki M.
        • Kumazawa M.
        • Kohsaka T.
        • Nakamura H.
        Effect of methotrexate-induced neutropenia on rat periapical lesion.
        Oral Surg Oral Med Oral Pathol. 1994; 77: 655-661
        • Kakehashi S.
        • Stanley H.R.
        • Fitzgerald R.J.
        The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats.
        Oral Surg Oral Med Oral Pathol. 1965; 20: 340-349
        • Itoh T.
        • Nakamura H.
        • Kishi J.
        • Hayakawa T.
        The activation of matrix metalloproteinases by a whole-cell extract from Prevotella nigrescens.
        J Endod. 2009; 35: 55-59
        • Woessner J.F.
        Matrix metalloproteinases and their inhibitors in connective tissue remodeling.
        FASEB J. 1991; : 2145-2154
        • Krane S.M.
        Clinical Importance of metalloproteinases and their inhibitors.
        Ann N Y Acad Sci. 1994; 732: 1-10
        • Birkedal-Hansen H.
        • Moore W.G.
        • Bodden M.K.
        • et al.
        Matrix metalloproteinases: a review.
        Crit Rev Oral Biol Med. 1993; 4: 197-250
        • Hannas A.R.
        • Pereira J.C.
        • Granjeiro J.M.
        • Tjäderhane L.
        The role of matrix metalloproteinases in the oral environment.
        Acta Odontologica Scandinavica. 2007; 65: 1-13
        • Hayakawa T.
        Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in development and disease of oral tissues.
        Dent in Japan. 1998; 34: 167-177
        • Page-McCaw A.
        • Ewald A.J.
        • Werb Z.
        Matrix metalloproteinases and the regulation of tissue remodelling.
        Nat Rev Mol Cell Biol. 2007; 8: 221-233
        • van der Zee E.
        • Everts V.
        • Beertsen W.
        Cytokine-induced endogenous procollagenase stored in the extracellular matrix of soft connective tissue results in a burst of collagen breakdown following its activation.
        J Peridontol Res. 1996; 3: 483-488
        • Chang Y.C.
        • Yang S.F.
        • Lai C.C.
        • Liu J.Y.
        • Hsieh Y.S.
        Regulation of matrix metalloproteinase production by cytokines, pharmacological agents and periodontal pathogens in human periodontal ligament fibroblast cultures.
        J Periodontal Res. 2002; 37: 196-203
        • Nishikawa M.
        • Yamaguchi Y.
        • Yoshitake K.
        • Saeki Y.
        Effects of TNF-alpha and prostaglandin E2 on the expression of MMPs in human periodontal ligament fibroblasts.
        J Periodontal Res. 2002; 37: 167-176
        • Rossa-Junior C.
        • Liu M.
        • Patil C.
        • Kirkwood K.L.
        MKK3/6-p38 MAPK negatively regulates murine MMP-13 gene expression induced by IL-1beta and TNF-alpha in immortalized periodontal ligament fibroblasts.
        Matrix Biol. 2005; 24: 478-488
        • Hernandez M.
        • Valenzuela M.A.
        • Lopez-Otin C.
        • et al.
        Matrix metalloproteinase-13 is highly expressed in destructive periodontal disease activity.
        J Periodontol. 2006; 77: 1863-1870
        • Sorsa T.
        • Tjaderhane L.
        • Konttinen Y.T.
        • et al.
        Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation.
        Ann Med. 2006; 38: 306-321
        • Lin S.K.
        • Kok S.H.
        • Kuo M.Y.P.
        • et al.
        Sequential expressions of MMP-1, TIMP-1, IL-6 and COX-2 genes in induced periapical lesions in rats.
        Eur J Oral Sci. 2002; 110: 246-253
        • Hong C.Y.
        • Lin S.K.
        • Kok S.H.
        • et al.
        The role of lipopolysaccharide in infectious bone resorption of periapical lesion.
        J Oral Pathol Med. 2004; 33: 162-169
        • 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
        • Shin S.J.
        • Lee J.
        • Baek S.H.
        • Lin S.S.
        Tissue levels of matrix metalloproteinases in pulps and periapical lesions.
        J Endod. 2002; 28: 313-315
        • Wahlgren J.
        • Salo T.
        • Teronen O.
        • Luoto H.
        • Sorsa T.
        • Tjäderhane L.
        Matrix metalloproteinase-8 (MMP-8) in pulpal and periapical inflammation and periapical root-canal exudates.
        Int Endod J. 2002; 35: 897-904
        • Leonardi R.
        • Caltabiano R.
        • Loreto C.
        Collagenase-3 (MMP-13) is expressed in periapical lesions: an immunohistochemical study.
        Int Endod J. 2005; 38: 297-301
        • Paula-Silva F.W.G.
        • D'Silva N.J.
        • Silva L.A.B.
        • Kapila Y.L.
        High matrix metalloproteinase activity is a hallmark of periapical granulomas.
        J Endod. 2009; 35: 1234-1242
        • Paula-Silva F.W.G.
        • Hassan B.
        • Silva L.A.B.
        • Leonardo M.R.
        • Wu M.K.
        Outcome of root canal treatment in dogs determined by periapical radiography and cone-beam computed tomography scans.
        J Endod. 2009; 35: 723-726
        • Paula-Silva F.W.G.
        • Wu M.-K.
        • Silva L.A.B.
        • Leonardo M.R.
        • Wesselink P.R.
        Accuracy of periapical radiography and cone-beam computed tomography in diagnosing apical periodontitis using histopathological findings as a gold standard.
        J Endod. 2009; 35: 1009-1012
        • Leonardo M.R.
        • Almeida W.A.
        • Ito I.Y.
        • Silva L.A.B.
        Radiographic and microbiologic evaluation of posttreatment apical and periapical repair of root canals of dogs' teeth with experimentally induced chronic lesion.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1994; 78: 232-238
        • Silva L.A.B.
        • Nelson-Filho P.
        • Leonardo M.R.
        • Rossi M.A.
        • Pansani C.A.
        Effect of calcium hydroxide on bacterial endotoxin in vivo.
        J Endod. 2002; 28: 94-98
        • Leonardo M.R.
        • Hernandez M.E.
        • Silva L.A.
        • Tanomaru-Filho M.
        Effect of a calcium hydroxide-based root canal dressing on periapical repair in dogs: a histological study.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102: 680-685
        • Siqueira Jr., J.F.
        • Lopes H.P.
        Mechanisms of antimicrobial activity of calcium hydroxide: a critical review.
        Int Endod J. 1999; 32: 361-369
        • Siqueira Jr., J.F.
        Strategies to treat infected root canals.
        J Calif Dent Assoc. 2001; 29: 825-837
        • Teronen O.
        • Salo T.
        • Konttinen Y.T.
        • et al.
        Identification and characterization of gelatinase/type IV collagenase in jaw cysts.
        J Oral Pathol Med. 1995; 24: 78-84
        • Teronen O.
        • Salo T.
        • Laitinen J.
        • et al.
        Characterization of interstitial collagenases in jaw cyst wall.
        Eur J Oral Sci. 1995; 103: 141-147
        • Carneiro E.
        • Menezes R.
        • Garlet G.P.
        • et al.
        Expression analysis of matrix metalloproteinase-9 in epithelialized and nonepithelialized apical periodontitis lesions.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009; 107: 127-132
        • Yang W.K.
        • Kim M.R.
        • Lee Y.
        • Son H.H.
        • Lee W.
        Effect of calcium hydroxide-treated Prevotella nigrescens on the gene expression of matrix metalloproteinase and its inhibitor in MG63 cells.
        J Endod. 2006; 32: 1142-1145
        • Van Lint P.
        • Libert C.
        Matrix metalloproteinase-8: cleavage can be decisive.
        Cytokine Growth Factor Rev. 2006; 17: 217-223
        • Huang F.M.
        • Yang S.F.
        • Chang Y.C.
        Up-regulation of gelatinases and tissue type plasminogen activator by root canal sealers in human osteoblastic cells.
        J Endod. 2008; 34: 291-294
        • Katebzadeh N.
        • Hupp J.
        • Trope M.
        Histological periapical repair after obturation of infected root canals in dogs.
        J Endod. 1999; 25: 364-368
        • Grecca F.S.
        • Leonardo M.R.
        • Silva L.A.B.
        • Tanomaru Filho M.
        • Borges M.A.G.
        Radiographic evaluation of periradicular repair after endodontic treatment of dog's teeth with induced periradicular periodontitis.
        J Endod. 2001; 27: 610-612
        • Holland R.
        • Otoboni-Filho J.A.
        • Souza V.
        • Nery M.J.
        • Bernabé P.F.
        • Dezan Jr., E.
        A comparison of one versus two appointment endodontic therapy in dogs' teeth with apical periodontitis.
        J Endod. 2003; 29: 121-124
        • De-Rossi A.
        • Silva L.A.B.
        • Leonardo M.R.
        • Rocha L.B.
        • Rossi M.A.
        Effect of rotary or manual instrumentation, with or without a calcium hydroxide / 1% chlorhexidine intracanal dressing, on the healing of experimentally induced chronic periapical lesions.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005; 99: 628-636
        • Silveira A.M.
        • Lopes H.P.
        • Siqueira Jr., J.F.
        • Macedo S.B.
        • Consolaro A.
        Periradicular repair after two-visit endodontic treatment using two different intracanal medications compared to single-visit endodontic treatment.
        Braz Dent J. 2007; 18: 299-304
        • Trope M.
        • Delano E.O.
        • Ørstavik D.
        Endodontic treatment of teeth with apical periodontitis: single vs. multivisit treatment.
        J Endod. 1999; 25: 345-350
        • Weiger R.
        • Rosendahl R.
        • Löst C.
        Influence of calcium hydroxide intracanal dressing on the prognosis of teeth with endodontically induced periapical lesions.
        Int Endod J. 2000; 33: 219-226
        • Peters L.B.
        • Wesselink P.R.
        Periapical healing of endodontically treated teeth in one and two visits obturated in the presence or absence of detectable microorganisms.
        Int Endod J. 2002; 35: 660-667
        • Figini L.
        • Lodi G.
        • Gorni F.
        • Gagliani M.
        Single versus multiple visits for endodontic treatment of permanent teeth.
        Cochrane Database Syst Rev. 2007; 17 (CD005296)
        • Naito T.
        Single or multiple visits for endodontic treatment?.
        Evid Based Dent. 2008; 9: 24
        • Estrela C.
        • Bueno M.R.
        • Leles C.R.
        • Azevedo B.
        • Azevedo J.R.
        Accuracy of cone beam computed tomography and panoramic and periapical radiography for detection of apical periodontitis.
        J Endod. 2008; 34: 273-279