Inflammation Research

, Volume 63, Issue 4, pp 317–323 | Cite as

Correlation of human S100A12 (EN-RAGE) and high-sensitivity C-reactive protein as gingival crevicular fluid and serum markers of inflammation in chronic periodontitis and type 2 diabetes

  • A. R. Pradeep
  • Santosh S. Martande
  • Sonender Pal Singh
  • Deepak Kumar Suke
  • Arjun P. Raju
  • Savitha B. Naik
Original Research Paper



The aim of the present study was to evaluate the levels and correlation of human S100A12 and high-sensitivity C-reactive protein (hs-CRP) in gingival crevicular fluid (GCF) and serum in chronic periodontitis (CP) subjects with and without type 2 diabetes mellitus (DM).

Materials and methods

A total of 44 subjects were divided into three groups: group 1 had 10 periodontally healthy subjects, group 2 consisted of 17 CP subjects and group 3 had 17 type 2 DM subjects with CP. GCF and serum levels of human S100A12 and hs-CRP were quantified using enzyme-linked immunosorbent assay and immunoturbidimetric analysis, respectively. The clinical outcomes evaluated were gingival index, probing depth and clinical attachment level and the correlations of the two inflammatory mediators with clinical parameters were evaluated.


Both human S100A12 and hs-CRP levels increased from group 1 to group 2 to group 3. The GCF and serum values of both these inflammatory mediators correlated positively with each other and with the periodontal parameters evaluated (p < 0.05).


Human S100A12 and hs-CRP can be considered as possible GCF and serum markers of inflammatory activity in CP and DM.


Chronic periodontitis Inflammation Diabetes mellitus Gingival crevicular fluid Biomarkers 



The authors are grateful to Mr. Manjunath Sharma, Institute of Statistical Services, Bangalore for providing the statistical analysis. The authors report no conflict of interests.


  1. 1.
    Holt SC, Ebersole JL. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the ‘red complex’, a prototype polybacterial pathogenic consortium in periodontitis. Periodontology. 2000;2005(38):72–122.Google Scholar
  2. 2.
    Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: assembling the players. Periodontology. 2000;1997(14):33–53.Google Scholar
  3. 3.
    Miyasaki KT. The neutrophil: mechanisms of controlling periodontal bacteria. J Periodontol. 1991;62:761–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Winer N, Sowers JR. Epidemiology of diabetes. J Clin Pharmacol. 2004;44:397–405.PubMedCrossRefGoogle Scholar
  5. 5.
    Taylor GW. Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective. Ann Periodontol. 2001;6:99–112.PubMedCrossRefGoogle Scholar
  6. 6.
    Loe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16:329–34.PubMedGoogle Scholar
  7. 7.
    Taylor GW, Burt BA, Becker MP, et al. Severe periodontitis and risk for poor glycemic control in patients with non-insulin dependent diabetes mellitus. J Periodontol. 1996;67(10 Suppl):1085–93.PubMedCrossRefGoogle Scholar
  8. 8.
    Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation? Amino Acids. 2009;36:381–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Guignard F, Mauel J, Markert M. Identification and characterization of a novel human neutrophil protein related to the S100 family. Biochem J. 1995;309:395–401.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Donato R. Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta. 1999;1450:191–231.PubMedCrossRefGoogle Scholar
  11. 11.
    Yang Z, Tao T, Raftery MJ, Youssef P, Di Girolamo N, Geczy CL. Proinflammatory properties of the human S100 protein S100A12. J Leukoc Biol. 2001;69:986–94.PubMedGoogle Scholar
  12. 12.
    Yang Z, Yan WX, Cai H, et al. S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol. 2007;119:106–14.PubMedCrossRefGoogle Scholar
  13. 13.
    Yilmaz Y, Yonal O, Eren F, Atug O, Over Hamzaoglu H. Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity. J Crohns Colitis. 2011;5:402–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Lander HM, Tauras JM, Ogiste JS, Hori O, Moss RA, Schmidt AM. Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. J Biol Chem. 1997;272:17810–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Hofmann MA, Drury S, Fu C, et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999;97:889–901.PubMedCrossRefGoogle Scholar
  16. 16.
    Foell D, Kane D, Bresnihan B, et al. Expression of the pro-inflammatory protein S100A12 (EN-RAGE) in rheumatoid and psoriatic arthritis. Rheumatology. 2003;42:1383–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Foell D, Kucharzik T, Kraft T, et al. Neutrophil derived S100A12 (EN-RAGE) is strongly expressed in chronic active inflammatory bowel disease. Gut. 2003;52:847–53.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Foell D, Seeliger S, Vogl T, et al. Expression of S100A12 (EN-RAGE) in cystic fibrosis. Thorax. 2003;58:613–7.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Heo SH, Choi YJ, Lee JH, Lee JM, Cho JY. S100A2 levels are related to human periodontitis. Mol Cells. 2011;32:445–50.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Noack B, Genco RJ, Trevisan M, Grossi S, Zambon JJ, De Nardin E. Periodontal infections contribute to elevated systemic C-reactive protein level. J Periodontol. 2001;72:1221–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Blüher M, Fasshauer M, Tönjes A, Kratzsch J, Schön MR, Paschke R. Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. Exp Clin Endocrinol Diabetes. 2005;113:534–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kosaki A, Hasegawa T, Kimura T, et al. Increased plasma S100A12 (EN-RAGE) levels in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2004;89:5423–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Löe H. The gingival index, the plaque index and the retention index systems. J Periodontol. 1967;38(6 Suppl):610–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Glavind L, Löe H. Errors in the clinical assessment of periodontal destruction. J Periodontal Res. 1967;2:180–4.PubMedCrossRefGoogle Scholar
  25. 25.
    WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.CrossRefGoogle Scholar
  26. 26.
    American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care. 2011;34(Suppl 1):S11–61.PubMedCentralCrossRefGoogle Scholar
  27. 27.
    Löe H, Holm-Pedersen P. Absence and presence of fluid from normal and inflamed gingivae. Periodontics. 1965;149:171–7.PubMedGoogle Scholar
  28. 28.
    Pradeep AR, Raghavendra N, Sharma A, et al. Association of serum and gingival crevicular fluid visfatin concentration in periodontal health and disease with type 2 diabetes. J Periodontol. 2012;83:629–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Lalla E, Lamster IB, Stern DM, Schmidt AM. Receptor for advanced glycation end products, inflammation, and accelerated periodontal disease in diabetes: mechanisms and insights into therapeutic modalities. Ann Periodontol. 2001;6:113–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-Reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286:327–34.PubMedCrossRefGoogle Scholar
  31. 31.
    Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, Fujii M, Tsuchihashi K, Goto H, Nakatani K, Yano Y. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1998;83:859–62.PubMedGoogle Scholar
  32. 32.
    Zinman B, Hanley AJ, Harris SB, Kwan J, Fantus IG. Circulating tumor necrosis factor-concentrations in a native Canadian population with high rates of type 2 diabetes mellitus. J Clin Endocrinol Metab. 1999;84:272–8.PubMedGoogle Scholar
  33. 33.
    Jokl R, Laimins M, Klein RL, Lyons TJ, Lopes-Virella MF, Colwell JA. Platelet plasminogen activator inhibitor 1 in patients with type II diabetes. Diabetes Care. 1994;17:818–23.PubMedCrossRefGoogle Scholar
  34. 34.
    Wu CL, Chen FL. Evaluation of C-reactive protein levels in serum and gingival crevicular fluid in type 2 diabetes patients with periodontitis. Shanghai Kou Qiang Yi Xue. 2009;18:132–5 (Chinese).PubMedGoogle Scholar
  35. 35.
    Megson E, Fitzsimmons T, Dharmapatni K, Bartold PM. C-reactive protein in gingival crevicular fluid may be indicative of systemic inflammation. J Clin Periodontol. 2010;37:797–804.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • A. R. Pradeep
    • 1
  • Santosh S. Martande
    • 1
  • Sonender Pal Singh
    • 1
  • Deepak Kumar Suke
    • 1
  • Arjun P. Raju
    • 2
  • Savitha B. Naik
    • 3
  1. 1.Department of PeriodonticsGovernment Dental College and Research InstituteBangaloreIndia
  2. 2.Bangalore Medical College and Research InstituteBangaloreIndia
  3. 3.Department of Conservative Dentistry and EndodonticsGovernment Dental College and Research InstituteBangaloreIndia

Personalised recommendations