Abstract
Periodontitis, a destructive periodontal inflammatory disease, negatively impacts oral-health related quality of life. It's characterized by the generation of inflammatory mediators and the excess-production of collagenolytic tissue-destructive enzymes (especially matrix metalloproteinases, MMPs). Many biomarkers can be used to define/diagnose disease progression. However, there is still a critical lack of specific, fast, and reliable biomarkers that correlate well with early response to treatment, which can be used to predict/monitor disease. Here, we report that an early marker, MMP-9, was found to be sensitive in response to a 1-month systemic therapy of CMC2.24, a novel chemically-modified curcumin, in beagle dogs with naturally-occurring periodontitis. In brief, eight adult female dogs with generalized periodontitis were distributed into placebo and treatment groups (n = 4/group). After a 1-h full-mouth scaling and root planing at time 0, placebo or CMC2.24 (10 mg/kg) capsules were orally-administered once/day for 1-month. Clinical periodontal parameters were measured at time 0 and 1-month; in addition, peripheral blood samples from these dogs were collected and analyzed for the pro-, activated-, and total-forms of MMP-9 by gelatin zymography. Interestingly, we found that the 1-month systemic therapy of CMC2.24 did appear to significantly reduce both pro- and activated-MMP-9 in peripheral blood at this early stage compared to placebo, prior to apparent clinical improvements seen at a later stage in a previous study (3-months). Thus, MMP-9 may serve as an early/sensitive biomarker that can precede/predict future clinical changes in disease severity and response to treatment which we observed in the long-term study in this dog model of natural periodontitis.
Highlights
Periodontitis is comprised of a broad range of chronic inflammatory events that destroy the supporting tissue structures of the teeth, leading to tooth loss, and contributes to systemic inflammation [1]
There was a slight trend of 4% reduction in probing depth (PD) measurements in the CMC2.24 treatment group at the 1-month time period, but this reduction was not statistically different at this time point, compared to placebotreated control group (p > 0.05, data not shown)
It should be noted that the severity of clinical parameters of periodontitis was significantly reduced at the 3-month timeperiod with this regimen of host modulation therapy (HMT) [p < 0.05, data already published [24]]
Summary
Periodontitis (periodontal disease) is comprised of a broad range of chronic inflammatory events that destroy the supporting tissue structures of the teeth (the gingiva, periodontal ligament and alveolar bone), leading to tooth loss, and contributes to systemic inflammation [1]. This concept has generally been referred to as “host modulation therapy (HMT),” meaning that the aim of treatment is to modify the host response by reducing those damaging aspects of the inflammatory/collagenolytic response that lead to tissue and bone destruction; HMT is an adjunct to the essential control of the microbial biofilm (dental plaque) To this purpose, the development of novel NON-antibiotic “formulations” of tetracyclines as a first generation of HMT (based on the mechanisms of action previously unrecognized in the medical and dental fields), and NON-antibiotic “compositions” of tetracyclines as the second generation of HMT, were introduced and developed for the management of periodontitis and various related and/or relevant systemic diseases [3, 4]. We determined whether biochemical markers at an early stage, i.e., destructive MMP9, are affected by CMC2.24 treatment before clinical changes become apparent months later
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