Abstract
BackgroundPeriodontitis is a set of chronic inflammatory diseases affecting the supporting structures of the teeth, during which a persistent release of lytic enzymes and inflammatory mediators causes a self-perpetuating vicious cycle of tissue destruction and repair. A matrix-based therapy using a heparan sulfate (HS) analogue called ReGeneraTing Agent (RGTA) replaces destroyed HS by binding to available heparin-binding sites of structural molecules, leading to restoration of tissue homeostasis in several inflammatory tissue injuries, including a hamster periodontitis model. MethodsThe ability of RGTA to restore the periodontium was tested in a model of Porphyromonas gingivalis-infected Balb/cByJ mice. After 12 weeks of disease induction, mice were treated weekly with saline or RGTA (1.5 mg/kg) for 8 weeks. Data were analyzed by histomorphometry. ResultsRGTA treatment restored macroscopic bone loss. This was related to (1) a significant reduction in gingival inflammation assessed by a decrease in infiltrated connective tissue, particularly in cells expressing interleukin 1ß, an inflammatory mediator selected as a marker of inflammation; (2) a normalization of bone resorption parameters, i.e. number, activation and activity of osteoclasts, and number of preosteoclasts; (3) a powerful bone formation reaction. The Sharpey's fibers of the periodontal ligament recovered their alkaline phosphatase coating. This was obtained while P. gingivalis infection was maintained throughout the treatment period. ConclusionsRGTA treatment was able to control the chronic inflammation characteristic of periodontitis and blocked destruction of periodontal structures. It ensured tissue regeneration with recovery of the periodontium's anatomy.
Highlights
Periodontitis is a set of chronic inflammatory diseases characterized by gingival inflammation, pocket formation, alveolar bone loss, and attachment apparatus destruction [1]
In this study, using a model of Porphyromonas gingivalis (P. gingivalis)-infected mice, our aim was to test the effectiveness of ReGeneraTing Agent (RGTA) treatment on (1) the bone metabolism, i.e. bone resorption and formation, with an emphasis on the recruitment and activity of the osteoclastic lineage, and (2) the inflammatory response, by evaluating the recruitment of cells expressing interleukin 1ß (IL-1ß) which we used as marker of inflammation, as it is the main cytokine expressed in the gingival tissues during periodontitis [15]
The two P. gingivalis-infected groups had elevated serum antibodies against the bacteria
Summary
Periodontitis is a set of chronic inflammatory diseases characterized by gingival inflammation, pocket formation, alveolar bone loss, and attachment apparatus destruction [1]. Local stimuli, such as pocket bacteria in the case of periodontitis, and products of matrix degradation prolong the inflammatory reaction, causing a persistent release of lytic enzymes and inflammatory mediators [3, 4, 5, 6, 7]. This exacerbates ECM destruction and causes sustained degradation of structure and repair-promoting molecules.
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