Gingival crevicular fluid as a source of biomarkers for periodontitis

Silvana P Barros, Ray Williams, Steven Offenbacher, Thiago Morelli, Silvana P Barros, Ray Williams, Steven Offenbacher, Thiago Morelli

Abstract

In evaluating the pathogenesis of periodontal diseases, the diagnostic potential of gingival crevicular fluid has been extensively explored during the last twenty years, from initially just confirming health and disease states to more recently investigating it as a potential prognostic tool. As host susceptibility is a critical determinant in periodontal disease pathogenesis, the inflammatory mediator levels present in gingival crevicular fluid represent relevant risk indicators for disease activity. Considerable work has been carried out to identify the many different cytokine inflammatory pathways and microbial stimuli that are associated with periodontal disease pathogenesis. Now, 'omics' approaches aim to summarize how these pathways interact and probably converge to create critical inflammatory networks. More recently, gingival crevicular fluid metabolomics appears promising as an additional diagnostic method. Biofilm structure and the host inflammatory response to the microbial challenge may induce specific inflammatory signatures. Host genetics and epigenetics may also modulate microbial colonization, adding to the multiplicity of potential causal pathways. Omics analyses of gingival crevicular fluid, measuring microbial and host interactions in association with the onset and progression of periodontal diseases, still show the potential to expand the landscape for the discovery of diagnostic, prognostic and therapeutic markers.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Schematic figure indicating the flux of gingival crevicular fluid through epithelial cells in the presence of a biofilm. In this microenvironment the exudate contributes to reorganization of subgingival biofilm and also carries inflammatory mediators and inflammatory cells to the periodontal pocket while harboring bacterial antigens, and enzymes of both host and bacterial origin.
Figure 2
Figure 2
Ilustration of GCF sampling sequence and use of Periotron®. Once the sites are isolated with cotton rolls and gently air-dried, the Perio® paper strips are inserted in the gingival sulcus for 30 seconds. The paper strips are then inserted in the Periotron 8000® device (Harco, Tustin, CA, USA), previously calibrated to each individual sample to obtain the fluid volume. Paper strips are then wrapped in aluminum foil, transferred to liquid nitrogen and stored at −80°C until assayed.

References

    1. Alfano MC. The origin of gingival fluid. J Theor Biol. 1974;47:127–136.
    1. Amar S, Oyaisu K, Li L, Van Dyke T. Moesin: a potential LPS receptor on human monocytes. J Endotoxin Res. 2001;7:281–286.
    1. Anguizola J, Matsuda R, Barnaby OS, Hoy KS, Wa C, DeBolt E, Koke M, Hage DS. Review: Glycation of human serum albumin. Clin Chim Acta. 2013;425:64–76.
    1. Arikan F, Buduneli N, Lappin DF. C-telopeptide pyridinoline crosslinks of type I collagen, soluble RANKL, and osteoprotegerin levels in crevicular fluid of dental implants with peri-implantitis: a case-control study. Int J Oral Maxillofac Implants. 2011;26:282–289.
    1. Attstrom R, Egelbert J. Presence of leukocytes within the gingival crevices during developing gingivitis in dogs. J Periodontal Res. 1971;6:110–114.
    1. Bader HI, Goldhaber P. The passage of intravenously administered tetracycline in the gingival sulcus of dogs. J Oral Ther Pharmacol. 1966;2:324–329.
    1. Baliban RC, Sakellari D, Li Z, DiMaggio PA, Garcia BA, Floudas CA. Novel protein identification methods for biomarker discovery via a proteomic analysis of periodontally healthy and diseased gingival crevicular fluid samples. J Clin Periodontol. 2012;39:203–212.
    1. Baliban RC, Sakellari D, Li Z, Guzman YA, Garcia BA, Floudas CA. Discovery of biomarker combinations that predict periodontal health or disease with high accuracy from GCF samples based on high-throughput proteomic analysis and mixed-integer linear optimization. J Clin Periodontol. 2013;40:131–139.
    1. Berridge MJ, O JL. Transporting Epithelia. Academic Press; 1972.
    1. Bickel M, Cimasoni G. The pH of human crevicular fluid measured by a new microanalytical technique. J Periodontal Res. 1985;20:35–40.
    1. Black GV. Special Dental Pathology. 2. Medico-Dental Publishing Co.; Chicago: 1920.
    1. Bostanci N, Heywood W, Mills K, Parkar M, Nibali L, Donos N. Application of label-free absolute quantitative proteomics in human gingival crevicular fluid by LC/MS E (gingival exudatome) J Proteome Res. 2010;9:2191–2199.
    1. Bostanci N, Ilgenli T, Emingil G, Afacan B, Han B, Toz H, Atilla G, Hughes FJ, Belibasakis GN. Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. J Clin Periodontol. 2007;34:370–376.
    1. Brill NB, H Passage of tissue fluid into human gingival pockets. Acta Odontol Scand. 1959;17:11–21.
    1. Brill N, K B. The passage of tissue fluid into the clinically healthy gingival pocket. Acta Odontol Scand. 1958;16:233–245.
    1. Champagne CM, Buchanan W, Reddy MS, Preisser JS, Beck JD, Offenbacher S. Potential for gingival crevice fluid measures as predictors of risk for periodontal diseases. Periodontol 2000. 2003;31:167–180.
    1. Chen HY, Cox SW, Eley BM. Cathepsin B, alpha2-macroglobulin and cystatin levels in gingival crevicular fluid from chronic periodontitis patients. J Clin Periodontol. 1998;25:34–41.
    1. Cimasoni G. The crevicular fluid. Monogr Oral Sci. 1974;3:1–122.
    1. Demmer RT, Behle JH, Wolf DL, Handfield M, Kebschull M, Celenti R, Pavlidis P, Papapanou PN. Transcriptomes in healthy and diseased gingival tissues. J Periodontol. 2008;79:2112–2124.
    1. Diamond JM, Tormey JM. Role of long extracellular channels in fluid transport across epithelia. Nature. 1966;210:817–820.
    1. Egelberg J. Gingival exudate measurements for evaluation of inflammatory changes of the gingiva. Odont Rev. 1964;15:381–398.
    1. Egelberg J. Cellular Elements in Gingival Pocket Fluid. Acta Odontol Scand. 1963;21:283–287.
    1. Engebretson SP, Grbic JT, Singer R, Lamster IB. GCF IL-1beta profiles in periodontal disease. J Clin Periodontol. 2002;29:48–53.
    1. Estreicher A, Broggiato A, Duroux P, Andersen E, Cimasoni G. Low molecular-weight proteins in human gingival crevicular fluid. Arch Oral Biol. 1996;41:733–738.
    1. Fine DH, Markowitz K, Fairlie K, Tischio-Bereski D, Ferrandiz J, Godboley D, Furgang D, Gunsolley J, Best A. Macrophage inflammatory protein-1alpha shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis. PLoS One. 2014;9:e98541.
    1. Giannobile WV. C-telopeptide pyridinoline cross-links. Sensitive indicators of periodontal tissue destruction. Ann N Y Acad Sci. 1999;878:404–412.
    1. Golub LM, Kleinberg I. Gingival crevicular fluid: a new diagnostic aid in managing the periodontal patient. Oral Sci Rev. 1976:49–61.
    1. Golub LM, Lee HM, Greenwald RA, Ryan ME, Sorsa T, Salo T, Giannobile WV. 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.
    1. Goodson JM. Gingival crevice fluid flow. Periodontol 2000. 2003;31:43–54.
    1. Grbic JT, Lamster IB, Fine JB, Lam KS, Celenti RS, Herrera-Abreu M, Singer RE. Changes in gingival crevicular fluid levels of immunoglobulin A following therapy: association with attachment loss. J Periodontol. 1999;70:1221–1227.
    1. Gustafsson A, Asman B, Bergstrom K. Elastase and lactoferrin in gingival crevicular fluid: possible indicators of a granulocyte-associated specific host response. J Periodontal Res. 1994;29:276–282.
    1. Holt SC, Ebersole JL. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the “red complex”, a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000. 2005;38:72–122.
    1. Jacob M, Chappell D. Reappraising Starling: the physiology of the microcirculation. Curr Opin Crit Care. 2013;19:282–289.
    1. Kajiura Y, Bando M, Inagaki Y, Nagata T, Kido J. Glycated albumin and calprotectin levels in gingival crevicular fluid from patients with periodontitis and type 2 diabetes. J Periodontol. 2014;85:1667–1675.
    1. Kebschull M, Demmer RT, Grun B, Guarnieri P, Pavlidis P, Papapanou PN. Gingival tissue transcriptomes identify distinct periodontitis phenotypes. J Dent Res. 2014;93:459–468.
    1. Kebschull M, Guarnieri P, Demmer RT, Boulesteix AL, Pavlidis P, Papapanou PN. Molecular differences between chronic and aggressive periodontitis. J Dent Res. 2013;92:1081–1088.
    1. Khalaf H, Lonn J, Bengtsson T. Cytokines and chemokines are differentially expressed in patients with periodontitis: possible role for TGF-beta1 as a marker for disease progression. Cytokine. 2014;67:29–35.
    1. Kido J, Bando M, Hiroshima Y, Iwasaka H, Yamada K, Ohgami N, Nambu T, Kataoka M, Yamamoto T, Shinohara Y, Sagawa I, Nagata T. Analysis of proteins in human gingival crevicular fluid by mass spectrometry. J Periodontal Res. 2012;47:488–499.
    1. Kinane DF, Darby IB, Said S, Luoto H, Sorsa T, Tikanoja S, Mantyla P. Changes in gingival crevicular fluid matrix metalloproteinase-8 levels during periodontal treatment and maintenance. J Periodontal Res. 2003;38:400–404.
    1. Kinney JS, Morelli T, Oh M, Braun TM, Ramseier CA, Sugai JV, Giannobile WV. Crevicular fluid biomarkers and periodontal disease progression. J Clin Periodontol. 2014;41:113–120.
    1. Koga M, Kasayama S. Clinical impact of glycated albumin as another glycemic control marker. Endocr J. 2010;57:751–762.
    1. Kontush A, Chapman MJ. Antiatherogenic small, dense HDL–guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med. 2006;3:144–153.
    1. Kowashi Y, Jaccard F, Cimasoni G. Sulcular polymorphonuclear leucocytes and gingival exudate during experimental gingivitis in man. J Periodontal Res. 1980;15:151–158.
    1. Krasse B. Serendipity or luck: stumbling on gingival crevicular fluid. J Dent Res. 1996;75:1627–1630.
    1. Krasse B, Egelberg J. The relative proportions of sodium, potassium and calcium in gingival pocket fluid. Acta Odontol Scand. 1962;20:143–152.
    1. Kung RT, Ochs B, Goodson JM. Temperature as a periodontal diagnostic. J Clin Periodontol. 1990;17:557–563.
    1. Lee MJ, Lee JK, Choi JW, Lee CS, Sim JH, Cho CH, Lee KH, Cho IH, Chung MH, Kim HR, Ye SK. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis. PLoS One. 2012;7:e38801.
    1. Levick JR. Revision of the Starling principle: new views of tissue fluid balance. J Physiol. 2004;557:704.
    1. Levick JR, Michel CC. Microvascular fluid exchange and the revised Starling principle. Cardiovasc Res. 2010;87:198–210.
    1. Lin SJ, Chen YL, Kuo MY, Li CL, Lu HK. Measurement of gp130 cytokines oncostatin M and IL-6 in gingival crevicular fluid of patients with chronic periodontitis. Cytokine. 2005;30:160–167.
    1. Lipowsky HH, Gao L, Lescanic A. Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation. Am J Physiol Heart Circ Physiol. 2011;301:H2235–2245.
    1. Loe H, Holm-Pedersen P. Absence and Presence of Fluid from Normal and Inflamed Gingivae. Periodontics. 1965;149:171–177.
    1. Loos BG, Tjoa S. Host-derived diagnostic markers for periodontitis: do they exist in gingival crevice fluid? Periodontol 2000. 2005;39:53–72.
    1. Mantyla P, Stenman M, Kinane DF, Tikanoja S, Luoto H, Salo T, Sorsa T. Gingival crevicular fluid collagenase-2 (MMP-8) test stick for chair-side monitoring of periodontitis. J Periodontal Res. 2003;38:436–439.
    1. Mena-Bravo A, Luque de Castro MD. Sweat: a sample with limited present applications and promising future in metabolomics. J Pharm Biomed Anal. 2014;90:139–147.
    1. Mogi M, Otogoto J, Ota N, Inagaki H, Minami M, Kojima K. Interleukin 1 beta, interleukin 6, beta 2-microglobulin, and transforming growth factor-alpha in gingival crevicular fluid from human periodontal disease. Arch Oral Biol. 1999;44:535–539.
    1. Nakashima K, Giannopoulou C, Andersen E, Roehrich N, Brochut P, Dubrez B, Cimasoni G. A longitudinal study of various crevicular fluid components as markers of periodontal disease activity. J Clin Periodontol. 1996;23:832–838.
    1. Offenbacher S, Barros S, Mendoza L, Mauriello S, Preisser J, Moss K, de Jager M, Aspiras M. Changes in gingival crevicular fluid inflammatory mediator levels during the induction and resolution of experimental gingivitis in humans. J Clin Periodontol. 2010;37:324–333.
    1. Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC, Beck JD. Periodontal disease at the biofilm-gingival interface. J Periodontol. 2007;78:1911–1925.
    1. Oliver RC, Holm-Pederen P, Loe H. The correlation between clinical scoring, exudate measurements and microscopic evaluation of inflammation in the gingiva. J Periodontol. 1969;40:201–209.
    1. Ozturk VO, Emingil G, Osterwalder V, Bostanci N. The actin-bundling protein L-plastin: a novel local inflammatory marker associated with periodontitis. J Periodontal Res. 2014
    1. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976;34:235–249.
    1. Reed RK, Rubin K. Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix. Cardiovasc Res. 2010;87:211–217.
    1. Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L. Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem. 1993;39:635–640.
    1. Schwartz J, Stinson FL, Parker RB. The passage of tritiated bacterial endotoxin across intact gingival crevicular epithelium. J Periodontol. 1972;43:270–276.
    1. Serres A. Cessai sur l’anatomie et la physiologie des dents, ou nouvelle theorie de la dentition. A Paris: Chez Méquignon-Marvis; 1817.
    1. Shimada Y, Tabeta K, Sugita N, Yoshie H. Profiling biomarkers in gingival crevicular fluid using multiplex bead immunoassay. Arch Oral Biol. 2013;58:724–730.
    1. Silva N, Dutzan N, Hernandez M, Dezerega A, Rivera O, Aguillon JC, Aravena O, Lastres P, Pozo P, Vernal R, Gamonal J. Characterization of progressive periodontal lesions in chronic periodontitis patients: levels of chemokines, cytokines, matrix metalloproteinase-13, periodontal pathogens and inflammatory cells. J Clin Periodontol. 2008;35:206–214.
    1. Silva-Boghossian CM, Colombo AP, Tanaka M, Rayo C, Xiao Y, Siqueira WL. Quantitative proteomic analysis of gingival crevicular fluid in different periodontal conditions. PLoS One. 2013;8:e75898.
    1. Socransky SS, Haffajee AD. Periodontal microbial ecology. Periodontol 2000. 2005;38:135–187.
    1. Takahashi N. Microbial ecosystem in the oral cavity: metabolic diversity in an ecological niche and its relationship with oral diseases. Int Congr Ser. 2005;1284:103–112.
    1. Tolo K. Transport across stratified nonkeratinized epithelium. J Periodontal Res. 1971;6:237–242.
    1. Tolo KJ. A study of permeability of gingival pocket epithelium to albumin in guinea pigs and Norwegian pigs. Arch Oral Biol. 1971;16:881–888.
    1. Waerhaug J. The source of mineral salts in subgingival calculus. J Dent Res. 1955;34:563–568.
    1. Waerhaug J, Steen E. The presence or absence of bacteria in gingival pockets and the reaction in healthy pockets to certain pure cultures; a bacteriological and histological investigation. Odontol Tidskr. 1952;60:1–24.
    1. Weinstein EM, I D, Salkind A, Oshrain HI, Pappas GD. Studies of Gingival Fluid. Periodontics. 1967;5:161–166.
    1. Yang C, Li H, Wang Z, Zhang W, Zhou K, Meng J, Zhao Y, Pan J, Lv X, Liang H, Jiang X. Glycated albumin is a potential diagnostic tool for diabetes mellitus. Clin Med. 2012;12:568–571.
    1. Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 2002;33:337–349.

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