Topic: aMMP-8 Oral Fluid PoC Test

  • Solomon O. Nwhator
  • Anna-Maria Heikkinen
  • Taina Tervahartiala
  • Dirk-Rolf Gieselmann
  • Jussi Leppilahti
  • Timo Sorsa


There is rising interest about influences of periodontal diseases on systemic health, while traditional measures cannot quantify periodontal inflammation. Confusing case definitions make the need to quantify periodontal inflammation greater than ever. Modern measures of periodontal inflammation depend on metabolism-mediated changes in salivary metabolites (salivary metabolomics)—an extra mile in salivary diagnostics.

Matrix metalloproteinase-8 fits well into the latest model of chronic periodontitis polymicrobial synergy and dysbiosis (PSD). Once instituted, host-derived mediators of inflammation perpetuate periodontal inflammation through cytokines and proteolytic enzymes including MMP-8, especially in its active form (aMMP-8). aMMP-8 correlates well with periodontal disease severity and activity, is effective in disease monitoring, and is the most abundant host-derived collagenolytic matrix metalloproteinase (MMP) in the saliva, mouth rinse, gingival crevicular and peri-implant sulcular fluids.

Based on these characteristics, Finnish periodontologists together with German and Finnish biotechnology companies invented a novel aMMP-8 chairside test kit using unstimulated whole mouth rinse as a substrate. The point-of-care (PoC) kit measures periodontitis quickly and accurately through a simple color change. The test detected initial periodontitis among adolescents, as well as chronic periodontitis in a variety of clinical scenarios relevant to important reproductive health parameters and had high validity and reliability. When applied to adult Nigerian and adolescent Finnish subjects, researchers stumbled upon a chance discovery—raised aMMP-8 level among close to 90% of Nigerian pregnant women.


aMMP-8 Point-of-care test Periodontitis Reproductive health 



This work was supported by TYH2016251 and TYH2017251 grants from the Helsinki University Hospital Research Funding, Helsinki, Finland, and Karolinska Institute, Stockholm, Sweden.

Timo Sorsa is an inventor of US patents 5652247, 57336341, 5866432, and 6143476. The other authors report no conflicts of interest related to this study.


  1. 1.
    Nwhator SO, Ashiwaju MO. Confusion in periodontitis diagnostic criteria. J Dent Orofac Res. 2013;1(1):36–43.CrossRefGoogle Scholar
  2. 2.
    Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A. Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol. 2008;35(8):668–73.CrossRefGoogle Scholar
  3. 3.
    Grover V, Kapoor A, Malhotra R, Kaur G. Clinical relevance of the advanced microbiologic and biochemical investigations in periodontal diagnosis: a critical analysis. J Oral Dis. 2014.
  4. 4.
  5. 5.
    Mikkonen JJW, Singh SP, Herrala M, et al. Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases. J Periodont Res. 2015;51:431–7.CrossRefGoogle Scholar
  6. 6.
    McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM. Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood. 2002;100(4):1160–7.PubMedGoogle Scholar
  7. 7.
    Sorsa T, Mäntylä P, Rönkä H, Kallio P, Kallis GB, Lundqvist C, Teronen O. Scientific basis of a matrix metalloproteinase-8 specific chair-side test for monitoring periodontal and peri-implant health and disease. Ann N Y Acad Sci. 1999;878(1):130–40.CrossRefGoogle Scholar
  8. 8.
    Sorsa T, Tjäderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis. 2004;10(6):311–8.CrossRefGoogle Scholar
  9. 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):306–21.CrossRefGoogle Scholar
  10. 10.
    Akbari G, Prabhuji MLV, Karthikeyan BV, Raghunatha K, Narayanan R. Analysis of matrix metalloproteinase-8 levels in gingival crevicular fluid and whole mouth fluid among smokers and nonsmokers using enzyme-linked immune-sorbent assay and a novel chair-side test. J Indian Soc Periodontol. 2015;19(5):525.CrossRefGoogle Scholar
  11. 11.
    Birkedal-Hansen H. Links between microbial colonization, inflammatory response and tissue destruction. In: Oral biology at the turn of the century: misconceptions, truths, challenges and prospects. Basel: Karger; 1998. p. 170–8.Google Scholar
  12. 12.
    Reynolds JJ, Meikle MC. Mechanisms of connective tissue matrix destruction in periodontitis. Periodontol 2000. 1997;14:144–57.CrossRefGoogle Scholar
  13. 13.
    Vasconcelos RC, Costa Ade L, Freitas Rde A, Bezerra BA, Santos BR, Pinto LP, Gurgel BC. Immunoexpression of HIF-1α and VEGF in periodontal disease and healthy gingival tissues. Braz Dent J. 2016;27(2):117–22.CrossRefGoogle Scholar
  14. 14.
    Rahnama M, Czupkałło Ł, Kozicka-Czupkałło M, Łobacz M. Gingival crevicular fluid–composition and clinical importance in gingivitis and periodontitis. Polish. J Public Health. 2014;124(2):96–8.Google Scholar
  15. 15.
    Lang NP, Tonetti MS. Periodontal risk assessment (PRA) for patients in supportive periodontal therapy (SPT). Oral Health Prev Dent. 2003;1(1):7–16.PubMedGoogle Scholar
  16. 16.
    Nwhator SO, Ayanbadejo PO, Umeizudike KA, Opeodu OI, Agbelusi GA, Olamijulo JA, Arowojolu MO, Sorsa T, Babajide BS, Opedun DO. Clinical correlates of a lateral-flow immunoassay oral risk indicator. J Periodontol. 2014;85(1):188–94.CrossRefGoogle Scholar
  17. 17.
    Heikkinen AM, Nwhator SO, Rathnayake N, Mäntylä P, Vatanen P, Sorsa T. Pilot study on oral health status as assessed by an active matrix metalloproteinase-8 chairside mouthrinse test in adolescents. J Periodontol. 2015;2:1–9.Google Scholar
  18. 18.
    Heikkinen AM, Kettunen K, Kovanen L, Haukka J, Elg J, Husu H, Tervahartiala T, Pussinen P, Meurman J, Sorsa T. Inflammatory mediator polymorphisms associate with initial periodontitis in adolescents. Clin Exp Dent Res. 2016;3:208–15.CrossRefGoogle Scholar
  19. 19.
    Heikkinen AM, Raivisto T, Kettunen K, Kovanen L, Haukka J, Pakbaznejad Esmaeili E, et al. Pilot study on the genetic background of an active matrix metalloproteinase-8 test in Finnish adolescents. J Periodontol. 2017;88(5):464–72.CrossRefGoogle Scholar
  20. 20.
    Heikkinen AM, Esmaeili EP, Kovanen L, Ruokonen H, Kettunen K, Haukka J, et al. Periodontal initial radiological findings of genetically predisposed Finnish adolescents. J Clin Diagn Res. 2017;11(7):ZC25–8.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Nwhator SO, Umeizudike KA, Ayanbadejo PO, Agbelusi GA, Arowojolu M, Sorsa T, Opeodu OI, Olamijulo JA, Akaba GO, Ekele BA. Black women’s predisposition to preterm birth; could we be near the answer. Int J Trop Dis Health. 2014;4(2):194–203.CrossRefGoogle Scholar
  22. 22.
    Nwhator SO, Opeodu OI, Ayanbadejo PO, Umeizudike KA, Olamijulo JA, Alade GO, Agbelusi GA, Arowojolu MO, Sorsa T. Could periodontitis affect time to conception? Ann Med Health Sci Res. 2014;4(5):817–22.CrossRefGoogle Scholar
  23. 23.
    Nwhator SO, Umeizudike KA, Ayanbadejo PO, Opeodu OI, Olamijulo JA, Sorsa T. Another reason for impeccable oral hygiene: oral hygiene-sperm count link. J Contemp Dent Pract. 2013;15(3):352–8.Google Scholar
  24. 24.
    Rosenow EC. Immunological and experimental studies on pneumococcus and staphylococcus endocarditis (“chronic septic endocarditis”). J Infect Dis. 1909;6:245–81.CrossRefGoogle Scholar
  25. 25.
    Bengen W, Hanen K. Die fokal infektion als problem der Allergie. Verhandl d deutsch Gesellsch f inn Med Kong. 1939;51:455.Google Scholar
  26. 26.
    Slauk A. Plaque disease and dentist. Leipzig: Gehlen; 1940. (article in German)Google Scholar
  27. 27.
    Linossier A, Thumann A, Bustos-Obregon E. Sperm immobilization by dental focus microorganisms. Andrologia. 1982;14:250–5.CrossRefGoogle Scholar
  28. 28.
    Bieniek KW, Riedel HH. Bacterial foci in the teeth, oral cavity, and jaw secondary effects (remote action) of bacterial colonies with respect to bacteriospermia and subfertility in males. Andrologia. 1993;25:159–62.CrossRefGoogle Scholar
  29. 29.
    Offenbacher S, Katz V, Fertik G, et al. Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol. 1996;67:1103–13.CrossRefGoogle Scholar
  30. 30.
    Kavoussi SK, West BT, Taylor GW, Lebovic DI. Periodontal disease and endometriosis: analysis of the National Health and Nutrition Examination Survey. Fertil Steril. 2009;91:335–42.CrossRefGoogle Scholar
  31. 31.
    Klinger A, Hain B, Yaffe H, Schonberger O. Periodontal status of males attending an in vitro fertilization clinic. J Clin Periodontol. 2011;38(6):542–6.CrossRefGoogle Scholar
  32. 32.
    Hart R, Doherty DA, Pennell CE, Newnham IA, Newnham JP. Periodontal disease: a potential modifiable risk factor limiting conception. Hum Reprod. 2012;27(5):1332–42.CrossRefGoogle Scholar
  33. 33.
    Oğuz F, Eltas A, Beytur A, Akdemir E, Uslu MÖ, Güneş A. Is there a relationship between chronic periodontitis and erectile dysfunction? J Sex Med. 2013;10(3):838–43.CrossRefGoogle Scholar
  34. 34.
    English J. Arginine and select phytonutrients enhance libido. Nutr Rev. https://nutritionrevieworg/2013/04/arginine-select-phytonutrients-enhance-libido/. Accessed 26 Aug 2017.
  35. 35.
    Thompson RJ. DHEA supplement for increasing women’s libido. FPO. 2003. Accessed 26 Aug 2017. US Patent application number 20030064123.
  36. 36.
    Holden JA, Attard TJ, Laughton KM, Mansell A, O'Brien-Simpson NM, Reynolds EC. Porphyromonas gingivalis lipopolysaccharide weakly activates M1 and M2 polarized mouse macrophages but induces inflammatory cytokines. Infect Immun. 2014;82(10):4190–203.CrossRefGoogle Scholar
  37. 37.
    Lourbakos A, Potempa J, Travis J, D’Andrea MR, Andrade-Gordon P, Santulli R, Mackie EJ, Pike RN. Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion. Infect Immun. 2001;69(8):5121–30.CrossRefGoogle Scholar
  38. 38.
    Kim NN, Cox JD, Baggio RF, Emig FA, Mistry SK, Harper SL, Speicher DW, Morris SM, Ash DE, Traish A, Christianson DW. Probing erectile function: S-(2-boronoethyl)-L-cysteine binds to arginase as a transition state analogue and enhances smooth muscle relaxation in human penile corpus cavernosum. Biochemistry. 2001;40(9):2678–88.CrossRefGoogle Scholar
  39. 39.
    Gheren LW, Cortelli JR, Rodrigues E, Holzhausen M, Saad WA. Periodontal therapy reduces arginase activity in saliva of patients with chronic periodontitis. Clin Oral Investig. 2008;12(1):67–72.CrossRefGoogle Scholar
  40. 40.
    American Sexual Health Association (ASHA). Erectile dysfunction. Retrieved from Accessed 26 Aug 2017.
  41. 41.
    De Nardin E. The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease. Ann Periodontol. 2001;6(1):30–40.CrossRefGoogle Scholar
  42. 42.
    Slade GD, Offenbacher S, Beck JD, Heiss G, Pankow JS. Acute-phase inflammatory response to periodontal disease in the US population. J Dent Res. 2000;79(1):49–57.CrossRefGoogle Scholar
  43. 43.
    Sharma A, Pradeep AR, Raju PA. Association between chronic periodontitis and vasculogenic erectile dysfunction. J Periodontol. 2011;82(12):1665–9.CrossRefGoogle Scholar
  44. 44.
    Keller JJ, Chung SD, Lin HC. A nationwide population-based study on the association between chronic periodontitis and erectile dysfunction. J Clin Periodontol. 2012;39(6):507–12.CrossRefGoogle Scholar
  45. 45.
    Colagar AH, Karimi F, Jorsaraei SG. Correlation of sperm parameters with semen lipid peroxidation and total antioxidants levels in astheno- and oligoasheno-teratospermic men. Iran Red Crescent Med J. 2013;15(9):780–5.Google Scholar
  46. 46.
    Camejo MI, Segnini A, Proverbio F. Interleukin-6 (IL-6) in seminal plasma of infertile men, and lipid peroxidation of their sperm. Arch Androl. 2001;47(2):97–101.CrossRefGoogle Scholar
  47. 47.
    McKinnon A, Black AY, Lortie K, Fleming NA. A case of adolescent pelvic inflammatory disease caused by a rare bacterium: Fusobacterium nucleatum. J Pediatr Adolesc Gynecol. 2013;26(6):e113–5.CrossRefGoogle Scholar
  48. 48.
    Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44.CrossRefGoogle Scholar
  49. 49.
    Socransky SS, Haffajee AD. Periodontal microbial ecology. Periodontol 2000. 2005;38(1):135–87.CrossRefGoogle Scholar
  50. 50.
    Han YW, Houcken W, Loos BG, Schenkein HA, Tezal M. Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer. Adv Dent Res. 2014;26(1):47–55.CrossRefGoogle Scholar
  51. 51.
    Liu H, Redline RW, Han YW. Fusobacterium nucleatum induces fetal death in mice via stimulation of TLR4-mediated placental inflammatory response. J Immunol. 2007;179(4):2501–8.CrossRefGoogle Scholar
  52. 52.
    Schenkein HA, Bradley JL, Purkall DB. Anticardiolipin in Porphyromonas gingivalis antisera causes fetal loss in mice. J Dent Res. 2013;92(9):814–8.CrossRefGoogle Scholar
  53. 53.
    Feairheller DL, Park JY, Sturgeon KM, Williamson ST, Diaz KM, Veerabhadrappa P, Brown MD. Racial differences in oxidative stress and inflammation: in vitro and in vivo. Clin Transl Sci. 2011;4(1):32–7.CrossRefGoogle Scholar
  54. 54.
    Morris M, Li L. Molecular mechanisms and pathological consequences of endotoxin tolerance and priming. Arch Immunol Ther Exp. 2012;60(1):13–8.CrossRefGoogle Scholar
  55. 55.
    Ferguson JF, Patel PN, Shah RY, Mulvey CK, Gadi R, Nijjar PS, Master SR. Race and gender variation in response to evoked inflammation. J Transl Med. 2013;11:63. Scholar
  56. 56.
    Paalani M, Lee JW, Haddad E, Tonstad S. Determinants of inflammatory markers in a bi-ethnic population. Ethn Dis. 2011;21(2):142.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Athayde N, Edwin SS, Romero R, Gomez R, Maymon E, Pacora P, Menon R. A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes. Am J Obstet Gynecol. 1998;179(5):1248–53.CrossRefGoogle Scholar
  58. 58.
    Shibahara H, Suzuki T, Kikuchi K, Hirano Y, Suzuki M. Serum matrix metalloproteinase and tissue inhibitor of metalloproteinase concentrations in infertile women achieved pregnancy following IVF-ET. Am J Reprod Immunol. 2005;54(4):186–92.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Solomon O. Nwhator
    • 1
  • Anna-Maria Heikkinen
    • 2
  • Taina Tervahartiala
    • 2
  • Dirk-Rolf Gieselmann
    • 3
  • Jussi Leppilahti
    • 2
  • Timo Sorsa
    • 2
    • 4
  1. 1.Department of Preventive and Community Dentistry, Faculty of Dentistry, College of Health SciencesObafemi Awolowo UniversityIfeNigeria
  2. 2.Department of Oral and Maxillofacial Diseases, Head and Neck CenterHelsinki University Hospital, University of HelsinkiHelsinkiFinland
  3. 3.Division of PeriodontologyDentognostics GmbHJenaGermany
  4. 4.Division of Periodontology, Department of Dental MedicineKarolinska InstitutetHuddingeSweden

Personalised recommendations