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.

Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study

“…This is in line with previous studies that showed clinical attachment loss occurring due to the RT [5,28,30]. MMP-8 is the most prevalent collagenolytic protease in the diseased periodontium and aMMP-8 the major mediator of periodontitis [15]. As the aMMP-8 levels stayed elevated after RT, it is possible that collagenolytic activity and the burden of aMMP-8 predisposes tissue for further periodontal damage.…”

“…With periodontal disease being increasingly recognized as a contributor in the pathophysiology of several systemic diseases, cancers, as well as risk factor for osteoradionecrosis, it is important to monitor and recognize worsened periodontal status after RT [31,32]. Periodontitis can be detected in real time with chairside/point-of-care aMMP-8 immunotest visually (−/+) and/or quantitatively in 5 min [15].…”

“…MMP-8 and -9 are the most abundant MMPs in periodontal tissues and oral fluids and when activated, they are responsible for the breakdown and remodeling of the extracellular matrix, such as collagen, elastin, and basement membranes. aMMP-8 (i.e., collagenase-2/neutrophil collagenase) is a catalytically competent collagenolytic protease and a major mediator of irreversible tissue destruction in periodontitis and can be utilized as a biomarker of periodontitis [15,16]. An increase in the expression of aMMP-8 in oral fluid diagnostic biomarker analysis shows the onset of the periodontal diseases and is related to the active progression of the disease.…”

Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

“…A chairside/point-of-care oral fluid test is an immunofluorescent or immunochromatographic assay employing different antibodies to detect both PMN and non-PMN-type MMP-8 isoforms, which may or not recognize different epitopes of the two isoforms [ 264 , 270 ]. This tool can be used for early disease detection as well as monitoring progression and evaluating therapeutic effects [ 271 ]. The current grading parameters allow us only to predict whether it is likely that the periodontal breakdown would occur in the future, but not the exact time when it would occur [ 272 ].…”

Point-of-care diagnostic devices for periodontitis – current trends and urgent need

“…For example, matrix metalloproteinases, namely MMP-8 and MMP-9, are significantly elevated in the GCF of periodontitis patients. [35][36][37] They are markers of collagen degradation, a classic symptom of periodontal disease. 35 However, it has been shown that it is the active form of MMP-8 (aMMP-8) that is a relevant biomarker for periodontitis and periimplantitis rather than the total or latent proMMP-8.…”