Active matrix metalloproteinase-8 (aMMP-8) point-of-care test (POCT) in the COVID-19 pandemic

Timo Sorsa, Vaibhav Sahni, Nurcan Buduneli, Shipra Gupta, Ismo T Räisänen, Lorne M Golub, Hsi-Ming Lee, Tommi Pätilä, Nagihan Bostanci, Jukka Meurman, Pirjo Pärnänen, Solomon O Nwhator, Mohita Singla, Krishan Gauba, Timo Sorsa, Vaibhav Sahni, Nurcan Buduneli, Shipra Gupta, Ismo T Räisänen, Lorne M Golub, Hsi-Ming Lee, Tommi Pätilä, Nagihan Bostanci, Jukka Meurman, Pirjo Pärnänen, Solomon O Nwhator, Mohita Singla, Krishan Gauba

Abstract

Introduction: Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular, and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis.

Areas covered: With this background, we aimed to review here the recent studies on practical, inexpensive, noninvasive and quantitative mouthrinse and GCF/PISF chair-side POCT lateral flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyzer) and how they help to detect, predict, monitor the course, treatment and prevention of periodontitis and peri-implantitis. The correlations of aMMP-8 POCT to other independent and catalytic activity assays of MMP-8 are also addressed.

Expert opinion: The mouthrinse aMMP-8 POCT can also detect prediabetes/diabetes and tissue destructive oral side-effects due to the head and neck cancers' radiotherapy. Chlorhexidine and doxycycline can inhibit collagenolytic human neutrophil and GCF aMMP-8. Furthermore, by a set of case-series we demonstrate the potential of mouthrinse aMMP-8 POCT to real-time/online detect periodontitis as a potential risk disease for coronavirus disease 2019 (COVID-19). The clinical interdisciplinary utilization of aMMP-8 POCT requires additional oral, medical, and interdisciplinary studies.

Keywords: Covid-19; Matrix metalloproteinase 8; biomarkers; diagnostics; mouth rinse; oral fluids; peri-implantitis; periodontitis.

Figures

Figure 1.
Figure 1.
Implantitis sites were tested before (+), two lines indicated by arrows and after (-), one line indicated by arrows surgical treatment by ImplantSafe; treatment caused positive sites (before, +) to be negative (after, -). Elevated active matrix metalloproteinase (aMMP)-8 levels in PISF detected by ImplantSafe positivity (before, +, two lines) and associated significantly with peri-implantitis and could be PoC -detected in 5 min by ImplantSafe
Figure 2.
Figure 2.
Inhibition of native type I collagen degradation by human neutrophil (PMN) active matrix metalloproteinase (aMMP)-8 and adult chronic periodontitis gingival crevicular fluid (GCF) aMMP-8 by chlorhexidine (CHX). Figure 2A, lane 1: 1.5 µM native type I collagen; lanes 2 and 3: 1.5 µM native type I collagen incubated with PMN aMMP-8 (400 ng [59]) for 8 h at 22°C; lanes 4 and 5: as lanes 2 and 3 but in the presence of 0.01%, 0.02%, and 0.04% CHX. Figure 2B, lane 1: 1.5 µM native type I collagen; lanes 2 and 3: 1.5 µM native type I collagen incubated with GCF aMMP-8 for 8 h at 22°C; lanes 4−8: as lanes 2 and 3 but in presence of 0.005%, 0.01%, 0.02%, and 0.04% CHX. β indicates intact native type I collagen dimers and α indicates intact native type I collagen monomers, βA, and αA indicate classical ¾ (75%) – degradation products resulting from catalytically competent (active) collagenolytic action of aMMP-8 on native type collagen. Observe the dose – dependent inhibition of type I collagenolytic activity of aMMP-8 by CHX
Figure 3.
Figure 3.
PerioSafe kit (negative: 20 ng/ml), a mouthrinse active matrix metalloproteinase (aMMP)-8 point-of-care test (POCT)
Figure 4.
Figure 4.
ImplantSafe kit (negative: 20 ng/ml), a site-specific peri-implant sulcular and gingival crevicular fluid (PISF/GCF) active matrix metalloproteinase (aMMP)-8 point-of-care test (POCT)

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    2. • Chlorhexidine used as a drug for periodontal diseases, inhibits MMP-8.

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    2. • Demonstration of Calprotectin POCT in periodontitis.

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    2. • Periodontitis can be regarded as a risk disease for COVID-19 infection.

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    2. • Confirms that chlorhexidine inhibits both MMP-2 and MMP-8.

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    2. • First paper to provide evidence that chlorhexidine inhibits both MMP-8 activity and MMP-8 activation.

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    2. • (Doxycycline via MMP-inhibition was found to be useful therapeutic agent for COVID-19 cases).

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    2. • Doxycycline via MMP-inhibition was found to be useful therapeutic agent for COVID-19 cases.

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    2. •• aMMP-8 POCT can be linked to oral dysbiotic periodontopathogens microbial proteolysis.

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    2. •• Periodontitis can be regarded as a risk disease for COVID-19 infection.

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