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

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.

Heparan Sulfate Glycosaminoglycan Is Predicted to Stabilize Inflammatory Infiltrate Formation and RANKL/OPG Ratio in Severe Periodontitis in Humans

“…The predictions of our model do not fully support the results of studies on the efficacy of supplementing degraded native HS GAG with its synthetic derivative (HS GAG mimetic) performed on experimental rodent models of periodontitis [ 16 , 48 , 49 , 50 ]. As reported, the administration of synthetic HS GAG was well tolerated by the animals, and the inflammation of soft periodontal tissues was significantly reduced.…”

“…Because chronically inflamed periodontal tissues exhibit persistent degradation of the ECM, the alternative to standard treatment is to rebuild the ECM using synthetic derivatives of ECM components. In a series of in vivo studies in rodent models of periodontitis, a synthetic HS GAG based on dextran polymers was administered to diseased animals by multiple subcutaneous injections [ 16 ]. In addition to the resolution of gingival tissue inflammation, regeneration of alveolar bone, periodontal ligament, and cementum was also reported.…”

ReGeneraTing Agents (rgta®) technology combined with antibiotics improves outcomes for infections in the upper limb

“…This indicates that the presence of bacteria does not necessarily inhibit healing from taking place and that once in motion, the healing process can overcome the infection. This has been shown in two models of periodontitis where partially destroyed maxillary bone and gingival tissues (including cementum) regenerated under treatment with OTR4120 in the presence of an ongoing infection 30,31 …”

“…This has been shown in two models of periodontitis where partially destroyed maxillary bone and gingival tissues (including cementum) regenerated under treatment with OTR4120 in the presence of an ongoing infection. 30,31 It is important for all healthcare practitioners who wish to use this product to be aware that thorough debridement of the wound is a prerequisite. Additionally, approximation of tissue aided by supportive tape enhances the process.…”

Simultaneous Quantitative Analysis of Ginsenosides Isolated from the Fruit of Panax ginseng C.A. Meyer and Regulation of HO-1 Expression through EGFR Signaling Has Anti-Inflammatory and Osteogenic Induction Effects in HPDL Cells

“…These Gram-negative bacteria are involved in several stages such as inflammation and alveolar bone loss due to the fact of periodontitis, tooth loss, and periodontal tissue destruction. The model for induction of periodontitis using Porphyromonas gingivalis (PG)-lipopolysaccharide (LPS) belonging to Gram-negative bacteria is known as a representative model in typical experimental periodontitis studies [ 6 ].…”