Active Matrix Metalloproteinase-8 (aMMP-8) Versus Total MMP-8 in Periodontal and Peri-Implant Disease Point-of-Care Diagnostics

Abstract

Active matrix metalloproteinase-8 (aMMP-8) is a promising biomarker candidate for the modern periodontal and peri-implant disease diagnostics utilizing the chairside/point-of-care oral fluid technologies. These rapid biomarker analysis technologies utilize gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), or mouth rinse as the oral fluid matrices that can be collected patient-friendly and non-invasively without causing bacteremia. aMMP-8, but not total or latent proMMP-8, has been shown to be a relevant biomarker to be implemented to the latest 2017 classification system of periodontitis and peri-implantitis. Thus, aMMP-8 point-of-care-testing (POCT)-but not total or latent proMMP-8-can be conveniently used as an adjunctive and preventive diagnostic tool to identify and screen the developing and ongoing periodontal and peri-implant breakdown and disease as well as predict its episodic progression. Similarly, aMMP-8 POCT provides an important tool to monitor the treatment effect of these diseases, but also other diseases such as head and neck cancer, where it can identify and predict the rapid tissue destructive oral side-effects during and after the radiotherapy. Additionally, recent studies support aMMP-8 POCT benefitting the identification of periodontitis and diabetes as the escalating risk diseases for COVID-19 infection. Overall, aMMP-8 POCT has launched a new clinical field in oral medicine and dentistry, i.e., oral clinical chemistry.

Keywords: aMMP-8; biomarker; matrix metalloproteinase; oral fluid; peri-implantitis; periodontitis; point-of-care diagnostics.

Figure 1

Graphical conclusion: mouth rinse, gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF) aMMP-8 levels utilized as the biomarker of periodontitis and peri-implantitis.

Figure 2

The association between the stage of periodontitis and (a) active matrix metalloproteinase (aMMP)-8 PoC test per the number of teeth present (aMMP-8/NTP), (b) aMMP-8 PoC test, and (c) total MMP-8 (ELISA) in 150 Greek adults as described in Sorsa et al. (2020) and Gupta et al. (2023) [26,42]. Kruskal–Wallis test was significant (p < 0.001) for aMMP-8 and aMMP-8/NTP, but not for total MMP-8 (p = 0.180). All significant (p < 0.05) pairwise post hoc comparisons (Dunn–Bonferroni test) are marked in the plots. The asterisk (*) indicates an extreme outlier (1.5× interquartile range) in the data. (b,c) reproduced from Sorsa et al. (2020) and Gupta et al. (2023), respectively [26,42] under the terms and conditions of the Creative Commons Attribution (CC BY) license https://creativecommons.org/licenses/by/4.0/, accessed on 28 August 2023.

Figure 3

Receiver operating characteristic (ROC) analysis presenting the diagnostic ability of aMMP-8 versus other biomarker candidates to discriminate peri-implantitis from healthy implant among (A) 26 peri-implantitis and 26 healthy dental implant patients as described in Lähteenmäki et al. (2020) [45] and (B) 26 peri-implantitis and 42 healthy dental implants as described in Lähteenmäki et al. (2022) [44]. Performance of a biomarker in ROC analysis is measured by the area under the individual ROC curves. (A,B) reproduced from Lähteenmäki et al. (2020) and Lähteenmäki et al. (2022) [44,45] under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/, accessed on 28 August 2023).

Figure 4

(A) Active matrix metalloproteinase (aMMP)-8 and (B) total MMP-8 levels in 150 Greek adults with 0–1 and ≥2 periodontal probing depths of ≥4 mm, aMMP-8 by point-of-care testing and total MMP-8 by ELISA were measured as described in Sorsa et al. (2020) and Gupta et al. (2023) [26,42]. The asterisk (*) indicates an extreme outlier (1.5× interquartile range) in the data.