Use of Salivary Markers to Heralding the Onset of Periodontal Disorders

There is an urgent need for an efficient system to diagnose periodontal disease in its early stages. A recent investigation on the prevalence of periodontitis in adults living in the USA revealed that almost 50% of the assayed individuals had periodontal disease. Research on the economic burden of oral diseases estimated that productivity losses due to severe periodontitis and, consequently, due to tooth loss in North America (US and Canada) amounted US$ 116 billion yearly. This pervasiveness of periodontitis can be attributed to the conventional method of diagnosis, which is entirely based upon recognizing observable signs - an assessment of the disease's history.

A crucial restraint of these observable parameters is that they do not detect present disease activity and, therefore, cannot provide a real-time evaluation of the disease status. The lack of evidence-based knowledge regarding periodontal diseases activity and level of progression may ultimately lead to unintentional clinical mismanagement [6]. Accordingly, there is an unmet requisite for easy and readily available methods to herald the periodontium health condition prior to the manifestation of disease clinical signs [7].

Periodontal diseases are identified as being resultant from an inflammatory, host-mediated response, associated with dysbiotic plaque biofilms. Within the inflammatory host response of periodontal diseases there is a group of enzymes that are key, the matrix metalloproteinases (MMP). The abundance of MMPs, more specifically MMP-8, in saliva of individuals with severe periodontitis has shown to be high. In physiological conditions, the activity of MMPs is tightly controlled by changes in the balance between their expression and the expression of their major tissue endogenous inhibitors, called TIMPs. In addition, the catalytic competence of MMPs is highly dependent on the concentration of specific metal ions, zinc and calcium, which justifies the use of the prefix "metal" to classify and group this proteinase superfamily. As MMP-inhibitory medication has been shown to reduce the levels of MMPs in oral fluids, we hypothesize that collection of oral fluid samples (i.e., saliva and/or gingival crevicular fluid) from individuals appertaining to different stages of periodontal diseases can identify a shift in the balance between MMPs and their tissue-regulatory factors.

The overall objective of this proposal is to contribute to enhance the predictability of periodontitis and identify a method to heralding its onset. We hypothesize that the levels of salivary MMPs and other factors modulating these enzymes activity relate with different clinical stages of periodontal disease. The questions this research will address are: Do the level of MMPs vary as a function of periodontium health state? Is there a quantifiable relationship between salivary MMPs and other markers, such as MMP-Tissue Inhibitors (TIMPs) and metal ions, in the context of periodontitis?

Thus, the specific aims of this purposed study are: