Periodontitis destructions are restored by synthetic glycosaminoglycan mimetic

Abstract

Periodontitis are bacterium-driven inflammatory diseases that destroy tooth-supporting tissues whose complete restoration is not currently possible. RGTA, a new class of agents, have this capacity in an animal model. Periodontitis was induced in hamsters and, starting 8 weeks later, injected RG1503, a glycosaminoglycan synthesized from a 40 kDa dextran behaving like a heparan sulfate mimetic (1.5 mg kg(-1) w(-1)) or saline for 8 weeks. The three periodontium compartments were evaluated by immunohistochemistry and morphometry. The gingival extracellular matrix disorganized by inflammation was restoring under treatment. The collagen network was repaired and resumed its previous organization. Fibrillin-1 expression was restored so that the elastic network rebuilt at a distance from the pocket and began to reconstruct near the pocket. Apoptotic cell numbers were decreased in the pocket epithelium, and more so in the infiltrated connective tissue. The continuity and the thickness of the basement membrane were restored and testified normalization of epithelium connective tissue interaction. The amount of alveolar bone increased around the first molar, and the interradicular bone was rebuilt. The root cementum was thickened and the number of proliferating cells in the periodontal ligament was increased close to the cementum. RG1503 treatment induces potent anabolic reactions in the extracellular matrices of the different tissues of the periodontium and recruitment of progenitors. In particular, the cell proliferation close to the root surface suggests the reformation of a functional attachment apparatus. These results demonstrate that RG1503 reverses the degenerative changes induced by inflammation and favors the conditions of a regenerative process. Thus, RGTA, a known matrix component mimetic and protector, may be considered as a new therapeutic tool to regenerate the tissues destroyed by periodontitis.

Insights on a new path of pre-mitochondrial apoptosis regulation by a glycosaminoglycan mimetic

“…11,[15][16][17] RGTAs are characterized by their capacity to surrogate natural GAGs destroyed by glycanase activities during stress. As expected, the GAG-mimetic decreased lipid peroxidation of cell membranes and restored the activity of aconitase close to control level (Figure 1) indicating that, at low concentrations, L929 were used for their sensitivity to TNF-a mediated cytotoxicity.…”

“…[14][15][16][17] Therefore they were also named RGTA s for ReGeneraTing Agents. Here, we postulate that GAG-mimetics can participate to regulation of apoptosis in a mechanism implicating cathepsins activation and lysosomal membrane permeabilization.…”

RGTA® or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine: from concept to curing patients

“…[33] Periodontitis-Restoration of gingival ECM.-Restoration of basement membrane.-Restoration of alveolar bone and interradicular bone.Lallam-Laroye et al . [34] Periodontitis-Restoration of alveolar bone.-Restoration of periodontal attachment.Lallam-Laroye et al . [35] Ethanol-induced gastric lesion and acetic acid induced colitis-Decreased severity of lesions.Meddahi et al .…”

Experimental Animal Models in Periodontology: A Review

“…Experimental periodontitis is easily obtained by feeding animals with a carbohydrate-rich diet. In this model, research focuses on microbiology and immunology [10]. …”