In the last few decades, circulating cell-free DNA (cfDNA) has been shown to have an important role in cell apoptosis or necrosis, including in the development and evolution of several tumors and inflammatory diseases in humans. In this regard, periodontitis, a chronic inflammatory disease that can induce the destruction of supporting components of the teeth, could represent a chronic inflammatory stimulus linked to a various range of systemic inflammatory diseases. Recently, a possible correlation between periodontal disease and cfDNA has been shown, representing new important diagnostic–therapeutic perspectives. During the development of periodontitis, cfDNA is released in biological fluids such as blood, saliva, urine and other body fluids and represents an important index of inflammation. Due to the possibility of withdrawing some of these liquids in a non-invasive way, cfDNA could be used as a possible biomarker for periodontal disease. In addition, discovering a proportional relationship between cfDNA levels and the severity of periodontitis, expressed through the disease extent, could open the prospect of using cfDNA as a possible therapeutic target. The aim of this article is to report what researchers have discovered in recent years about circulating cfDNA in the development, evolution and therapy of periodontitis. The analyzed literature review shows that cfDNA has considerable potential as a diagnostic, therapeutic biomarker and therapeutic target in periodontal disease; however, further studies are needed for cfDNA to be used in clinical practice.
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