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Periodontal reconstruction by heparan sulfate mimetic-based matrix therapy in Porphyromonas gingivalis-infected mice

Abstract : Background - Periodontitis 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. Methods - The ability of RGTA to restore the periodontium was tested in a model of -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. Results - RGTA 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 infection was maintained throughout the treatment period. Conclusions - RGTA 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.
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Submitted on : Friday, July 19, 2019 - 1:12:14 PM
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Benjamin R Coyac, Laurent Detzen, Philippe Doucet, Brigitte Baroukh, Annie Llorens, et al.. Periodontal reconstruction by heparan sulfate mimetic-based matrix therapy in Porphyromonas gingivalis-infected mice. Heliyon, Elsevier 2018, 4 (8), pp.e00719. ⟨10.1016/j.heliyon.2018.e00719⟩. ⟨hal-01862580⟩

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