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Heliyon. 2018 Aug 6;4(8):e00719. doi: 10.1016/j.heliyon.2018.e00719. eCollection 2018 Aug.

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

Author information

1
EA2496 Laboratoire Pathologies, Imagerie et Biothérapies oro-faciales, Faculté de Chirurgie Dentaire, Université Paris Descartes, Sorbonne Paris Cité, Montrouge, France.
2
Assistance Publique - Hôpitaux de Paris, Paris, France.
3
Private Practice in Periodontics, Paris, France.
4
U-1241 Inserm - U-1341 Inra, Université de Rennes 1, Rennes, France.
5
OTR3, Paris, France.

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 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.

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 P. gingivalis 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.

KEYWORDS:

Bioengineering; Biotechnology; Cell biology; Dentistry; Immunology; Physiology

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