Periodontal treatment reduces matrix metalloproteinase levels in localized aggressive periodontitis

Patricia Furtado Gonçalves, Hong Huang, Suzanna McAninley, Barnett Alfant, Peter Harrison, Ikramuddin Aukhil, Clay Walker, Luciana Macchion Shaddox, Patricia Furtado Gonçalves, Hong Huang, Suzanna McAninley, Barnett Alfant, Peter Harrison, Ikramuddin Aukhil, Clay Walker, Luciana Macchion Shaddox

Abstract

Background: Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal breakdown and inflammation. High MMP levels in African-American children with localized aggressive periodontitis (LAgP) have been reported previously by the present authors. However, little is known about MMP reductions in gingival crevicular fluid (GCF) after therapy. This study aims to evaluate MMP levels in the GCF after treatment of LAgP and to correlate these levels with clinical response.

Methods: GCF samples were collected from 29 African-American individuals diagnosed with LAgP. GCF was collected from one diseased site (probing depth [PD] >4 mm, bleeding on probing [BOP], and clinical attachment level ≥ 2 mm) and one healthy site (PD ≤ 3 mm, no BOP) from each individual at baseline and 3 and 6 months after periodontal treatment, which consisted of full-mouth scaling and root planing (SRP) and systemic antibiotics. The volume of GCF was controlled using a calibrated gingival fluid meter, and levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 were assessed using fluorometric kits.

Results: MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13 levels were reduced significantly up to 6 months, comparable to healthy sites at the same point. Significant correlations were noted between MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 levels and percentage of sites with PD >4 mm. MMP-3, MMP-12, and MMP-13 levels also correlated with mean PD of affected sites.

Conclusion: Treatment of LAgP with SRP and systemic antibiotics was effective in reducing local levels of specific MMPs in African-American individuals, which correlated positively with some clinical parameters.

Trial registration: ClinicalTrials.gov NCT01330719.

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this manuscript.

Conflict of Interest:

The authors state that they have no conflict of interests, financial or commercial relationships to declare.

Figures

Figure 1
Figure 1
(A–G). Clinical parameters at baseline and after treatment. PD>4mm = mean % of sites with PD>4mm. Mean PD sites= Mean pocket depth of sites with PD>4mm; Mean PD all= mean PD of all sites; Mean CAL= mean clinical attachment level of affected sites; BoP=bleeding on probing; PD site = mean pocket depth from diseased site sampled for GCF. Values in boxes are represented as Means (horizontal bars) ± Standard deviation (whiskers). BL= baseline (n=29); 3mo 3 months (n=16); 6mo= 6 months (n=22). Statistically significant differences* (One Way ANOVA, p<0.05) are represented as horizontal bars between timepoints by Dunn’s multiple comparisons. # indicates an overall significant difference in ANOVA on ranks.
Figure 2
Figure 2
(A–G). MMP levels at baseline and after treatment. Values (dots: Diseased sites; triangles: Healthy sites) are represented as Means (horizontal bars) ± Standard deviation (whiskers). BL= baseline; 3mo= 3 months; 6mo= 6 months. Statistically significant differences* (Kruskal Wallis test) are represented as horizontal bars between timepoints. Stars above healthy sites represent differences between diseased and healthy sites. P-values are represented as *(p<0.05), **(p<0.01) and ***(p<0.0001). #indicates an overall difference found in ANOVA on ranks (p<0.05).

References

    1. Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999;4:1–6.
    1. Lang NP, Bartold M, Cullinan M, et al. Consensus Report: Aggressive Periodontitis. Ann Periodontol. 1999;4:53.
    1. Albandar JM, Tinoco EM. Global epidemiology of periodontal diseases in children and young persons. Periodontol 2000. 2002;29:153–176.
    1. Tonetti MS, Mombelli A. Early-onset periodontitis. Ann Periodontol. 1999;4:39–53.
    1. Lang N, Bartold M, Cullinan M, et al. Consensus Report: Aggressive Periodontitis. Annals of Periodontology. 1999;4:53.
    1. Haubek D, Ennibi OK, Poulsen K, Vaeth M, Poulsen S, Kilian M. Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans in Morocco: a prospective longitudinal cohort study. Lancet. 2008;371:237–242.
    1. Shaddox LM, Huang H, Lin T, et al. Microbiological Characterization in Children with Aggressive Periodontitis. J Dent Res. 2012
    1. Shaddox L, Wiedey J, Bimstein E, et al. Hyper-responsive phenotype in localized aggressive periodontitis. J Dent Res. 2010;89:143–148.
    1. Shaddox LM, Wiedey J, Calderon NL, et al. Local inflammatory markers and systemic endotoxin in aggressive periodontitis. J Dent Res. 2011;90:1140–1144.
    1. Sodek J, Overall CM. Matrix metalloproteinases in periodontal tissue remodelling. Matrix Suppl. 1992;1:352–362.
    1. Birkedal-Hansen H. Role of matrix metalloproteinases in human periodontal diseases. J Periodontol. 1993;64:474–84.
    1. Sorsa T, Tjaderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis. 2004;10:311–318.
    1. Uitto VJ, Overall CM, McCulloch C. Proteolytic host cell enzymes in gingival crevice fluid. Periodontol 2000. 2003;31:77–104.
    1. Narayanan AS, Page RC. Connective tissues of the periodontium: a summary of current work. Coll Relat Res. 1983;3:33–64.
    1. Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993;4:197–250.
    1. Ingman T, Tervahartiala T, Ding Y, et al. Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients. J Clin Periodontol. 1996;23:1127–1132.
    1. Leppert D, Lindberg RL, Kappos L, Leib SL. Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis. Brain Res Brain Res Rev. 2001;36:249–257.
    1. Villela B, Cogen RB, Bartolucci AA, Birkedal-Hansen H. Collagenolytic activity in crevicular fluid from patients with chronic adult periodontitis, localized juvenile periodontitis and gingivitis, and from healthy control individuals. J Periodontal Res. 1987;22:381–389.
    1. Larivee J, Sodek J, Ferrier JM. Collagenase and collagenase inhibitor activities in crevicular fluid of patients receiving treatment for localized juvenile periodontitis. J Periodontal Res. 1986;21:702–715.
    1. Kryshtalskyj E, Sodek J, Ferrier JM. Correlation of collagenolytic enzymes and inhibitors in gingival crevicular fluid with clinical and microscopic changes in experimental periodontitis in the dog. Arch Oral Biol. 1986;31:21–31.
    1. Alfant B, Shaddox LM, Tobler J, Magnusson I, Aukhil I, Walker C. Matrix metalloproteinase levels in children with aggressive periodontitis. J Periodontol. 2008;79:819–826.
    1. Emingil G, Han B, Ozdemir G, et al. Effect of azithromycin, as an adjunct to nonsurgical periodontal treatment, on microbiological parameters and gingival crevicular fluid biomarkers in generalized aggressive periodontitis. J Periodontal Res. 2012;47:729–739.
    1. Skurska A, Pietruska MD, Paniczko-Drężek A, et al. Evaluation of the influence of ozonotherapy on the clinical parameters and MMP levels in patients with chronic and aggressive periodontitis. Adv Med Sci. 2010;55:297–307.
    1. Ingman T, Sorsa T, Lindy O, Koski H, Konttinen YT. Multiple forms of gelatinases/type IV collagenases in saliva and gingival crevicular fluid of periodontitis patients. J Clin Periodontol. 1994;21:26–31.
    1. Mäkelä M, Salo T, Uitto VJ, Larjava H. Matrix metalloproteinases (MMP-2 and MMP-9) of the oral cavity: cellular origin and relationship to periodontal status. J Dent Res. 1994;73:1397–1406.
    1. Korostoff JM, Wang JF, Sarment DP, Stewart JC, Feldman RS, Billings PC. Analysis of in situ protease activity in chronic adult periodontitis patients: expression of activated MMP-2 and a 40 kDa serine protease. J Periodontol. 2000;71:353–360.
    1. Ejeil AL, Igondjo-Tchen S, Ghomrasseni S, Pellat B, Godeau G, Gogly B. Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy and diseased human gingiva. J Periodontol. 2003;74:188–195.
    1. Pozo P, Valenzuela MA, Melej C, et al. Longitudinal analysis of metalloproteinases, tissue inhibitors of metalloproteinases and clinical parameters in gingival crevicular fluid from periodontitis-affected patients. J Periodontal Res. 2005;40:199–207.
    1. Hannas AR, Pereira JC, Granjeiro JM, Tjäderhane L. The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand. 2007;65:1–13.
    1. Golub LM, Lee HM, Greenwald RA, et al. A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments and specific collagenases in gingival crevicular fluid during adult periodontitis. Inflamm Res. 1997;46:310–319.

Source: PubMed

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