Diagnostic potential and future directions of matrix metalloproteinases as biomarkers in gingival crevicular fluid of oral and systemic diseases

Gingival crevicular fluid (GCF) is a physiological fluid and an inflammatory serum exudate derived from the gingival plexus of blood vessels and mixed with host tissues and subgingival plaque flows. In addition to proteins, GCF contains a diverse population of cells, including desquamated epithelial cells, cytokines, electrolytes, and bacteria from adjacent plaques. Recently, matrix metalloproteinases(MMPs), which are endopeptidases that are active against extracellular macromolecules, in GCF have been revealed as potential utility biomarkers for the diagnosis and follow-up of oral and systemic diseases, thereby facilitating the early evaluation of malignancy risk and the monitoring of disease progression and treatment response. Tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of matrixins that participate in the regulation of local activities of MMPs in tissues. This review provides an overview of the latest findings on the diagnostic and prognostic values of MMPs and TIMPs in GCF of oral and systemic diseases, including periodontal disease, pulpitis, peri-implantitis and cardiovascular disease as well as the extraction, detection and analytical methods for GCF.