Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis

Abstract

Periodontitis is an inflammatory disease of the periodontium. Any imbalance between the matrix metalloproteinases (MMPs) secreted by neutrophils and tissue inhibitors initiates the destruction of collagen in gum tissue, leading to chronic periodontitis. This study aimed to correlate salivary levels of MMP-8 and periodontal parameters of chronic periodontitis to establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis. The study involved 40 subjects visiting the periodontic OPD of Dr. Ziauddin Ahmad Dental College and Hospital, located in Aligarh, U.P., India, from 2011 to 2012. The subjects were divided into two groups: group I consisted of 20 periodontally healthy subjects (controls) while group II consisted of 20 patients with chronic periodontitis. Chronic periodontitis was assessed on the basis of several periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). Around 3 ml of unstimulated and whole expectorated saliva was collected for MMP-8 estimation by ELISA using Quantikine human total MMP-8 immunoassay kits. Data were analyzed using STATISTICA (Windows version 6) software. Salivary MMP-8 levels of groups I and II were 190.91±143.89 ng/ml and 348.26±202.1 ng/ml, respectively. The MMP-8 levels and periodontal status (PPD, CAL, GI, and PI) of groups I and II showed positive and significant correlations (for PPD, r = 0.63, P<0.001; for CAL, r = 0.54, P<0.001; for GI, r = 0.49, P<0.001; and for PI, r = 0.63, P<0.001). The results of this study demonstrate elevated concentrations of MMP-8 in individuals with chronic periodontitis.

Keywords

matrix metalloproteinase-8 / chronic periodontitis / pocket probing depth / clinical attachment level / gingival index / plaque index

References

[1] Nunn ME. Understanding the etiology of periodontitis: an overview of periodontal risk factors. Periodontol 2000 2003; 32(1): 11–23

[2] Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol 1996; 1(1): 821–878

[3] Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang , Elashoff D, Wei R, Loo JA, Wong DT. Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res 2008; 14(19): 6246–6252

[4] Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, Eisele D, Abemayor E, Elashoff D, Park NH, Wong DT. Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res 2004; 10(24): 8442–8450

[5] Hu S, Wang J, Meijer J, Ieong S, Xie Y, Yu T, Zhou H, Henry S, Vissink A, Pijpe J, Kallenberg C, Elashoff D, Loo JA, Wong DT. Salivary proteomic and genomic biomarkers for primary Sjögren’s syndrome. Arthritis Rheum 2007; 56(11): 3588–3600

[6] Armitage GC. Periodontal diagnoses and classification of periodontal diseases. Periodontol 2000 2004; 34(1): 9–21

[7] Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: current state and future directions. Periodontol 2000 2009; 50(1): 52–64

[8] Kraft-Neumärker M, Lorenz K, Koch R, Hoffmann T, Mäntylä P, Sorsa T, Netuschil L. Full-mouth profile of active MMP-8 in periodontitis patients. J Periodontal Res 2012; 47(1): 121–128

[9] Sorsa T, Tjäderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, Golub LM, Brown DL, Mäntylä P. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med 2006; 38(5): 306–321

[10] Herr AE, Hatch AV, Throckmorton DJ, Tran HM, Brennan JS, Giannobile WV, Singh AK. Microfluidic immunoassays as rapid saliva-based clinical diagnostics. Proc Natl Acad Sci USA 2007; 104(13): 5268–5273

[11] Ingman T, Tervahartiala T, Ding Y, Tschesche H, Haerian A, Kinane DF, Konttinen YT, Sorsa T. Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients. J Clin Periodontol 1996; 23(12): 1127–1132

[12] Heikkinen AM, Sorsa T, Pitkäniemi J, Tervahartiala T, Kari K, Broms U, Koskenvuo M, Meurman JH. Smoking affects diagnostic salivary periodontal disease biomarker levels in adolescents. J Periodontol 2010; 81(9): 1299–1307

[13] Sorsa T, Tjäderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 2004; 10(6): 311–318

[14] Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141(1): 52–67

[15] Löe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol 1967; 38(6): 610–616

[16] Löe H, Silness J. Periodontal disease in pregnancy. Prevelance and severity. Acta Odontol Scand 1963; 21(6): 533–551

[17] Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci 1993; 694: 72–77

[18] Quantikine Human Total MMP-8 Immunnoassay; Catalog Number DMP800: R&D Systems, Inc. 614 McKinley Place NE, Minneapolis, MN55413, USA

[19] Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: a cross-sectional study. J Am Dent Assoc 2006; 137(3): 322–329

[20] Oberg SG, Izutsu KT, Truelove EL. Human parotid saliva protein composition: dependence on physiological factors. Am J Physiol 1982; 242(3): G231–G236

[21] Sorsa T, Hernández M, Leppilahti J, Munjal S, Netuschil L, Mäntylä P. Detection of gingival crevicular fluid MMP-8 levels with different laboratory and chair-side methods. Oral Dis 2010; 16(1): 39–45

[22] Sorsa T, Tervahartiala T, Leppilahti J, Hernandez M, Gamonal J, Tuomainen AM, Lauhio A, Pussinen PJ, Mäntylä P. Collagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases. Therapeutic response to non-antimicrobial properties of tetracyclines. Pharmacol Res 2011; 63(2): 108–113

[23] Salminen A, Gursoy UK, Paju S, Hyvärinen K, Mäntylä P, Buhlin K, Könönen E, Nieminen MS, Sorsa T, Sinisalo J, Pussinen PJ. Salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis. J Clin Periodontol 2014; 41(5): 442–450

[24] Tonetti MS, Freiburghaus K, Lang NP, Bickel M. Detection of interleukin-8 and matrix metalloproteinases transcripts in healthy and diseased gingival biopsies by RNA/PCR. J Periodontal Res 1993; 28(6): 511–513

[25] Kuula H, Salo T, Pirilä E, Tuomainen AM, Jauhiainen M, Uitto VJ, Tjäderhane L, Pussinen PJ, Sorsa T. Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis. Infect Immun 2009; 77(2): 850–859

[26] Rathnayake N, Akerman S, Klinge B, Lundegren N, Jansson H, Tryselius Y, Sorsa T, Gustafsson A. Salivary biomarkers of oral health: a cross-sectional study. J Clin Periodontol 2013; 40(2): 140–147

[27] Gursoy UK, Könönen E, Huumonen S, Tervahartiala T, Pussinen PJ, Suominen AL, Sorsa T. Salivary type I collagen degradation end-products and related matrix metalloproteinases in periodontitis. J Clin Periodontol 2013; 40(1): 18–25

[28] Javed F, Ahmed HB, Saeed A, Mehmood A, Bain C. Whole salivary interleukin-6 and matrix metalloproteinase-8 levels in patients with chronic periodontitis with and without prediabetes. J Periodontol 2014; 85(5): e130–e135

Acknowledgements

This study was self-funded.

Namita Gupta, N.D. Gupta, Akash Gupta, Saif Khan, and Neha Bansal declare that they have no conflicts of interest. All of the procedures used in this study were in accordance with the ethical standards of the Responsible Committee on Human Experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients prior to their participation in the study.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg