exenatide and Periodontitis

With the impaired regenerative potential in patients with diabetes mellitus (DM), Periodontal ligament stem cells (PDLSCs) are regarded as an attractive source of stem cells for periodontal cytotherapy. Recent studies have shown that Exendin-4 (Ex-4) exerts cell-protective effects and bone remodeling ability on many types of cells. The aim of this study was to investigate whether Ex-4 alleviates the inhibition of high glucose on the proliferation and osteogenic differentiation of PDLSCs.. PDLSCs were incubated in medium supplemented with 5.5 mM d-glucose (NG), 30 mM d-glucose (HG), NG plus Ex-4, and HG plus different concentration (1, 10, 20, 100 nM) of Ex-4 respectively. Cell proliferation was detected by CCK-8 assay and cell cycle analysis. Osteogenesis was assessed by Alizarin Red S staining and evaluation of the mRNA expression of Runx2, ALP and Osx at day 7, 14 and 21. Intracellular level of reactive oxygen species (ROS) was detected using 5-(and-6)-chloromethyl-2',7'-dichlorodihydro-fluorescein diacetate (CMH2DCF-DA).. The proliferation ability, mineralized nodules forming capacity and the mRNA expression of Runx2, ALP and Osx of PDLSCs in HG group were decreased, the ROS level was increased compared to NG group. With the treatment of Ex-4, the HG-inhibited proliferation ability and osteogenic differentiation ability of PDLSCs were significantly reversed, the HG-increased ROS level could be down-regulated. Moreover, Ex-4 enhanced the osteogenic differentiation of normal PDLSCs.. Ex-4 alleviates the inhibitory effect of HG on the proliferation and osteoblastic differentiation of PDLSCs, and has a significant enhance in the osteoblastic differentiation of normal PDLSCs, giving new insights into the possible therapeutic method of diabetic periodontitis.

Topics: Cell Cycle; Cell Differentiation; Cell Proliferation; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Exenatide; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucose; Humans; Osteoblasts; Osteogenesis; Peptides; Periodontal Ligament; Periodontitis; Reactive Oxygen Species; Sp7 Transcription Factor; Stem Cells; Transcription Factors; Venoms

New drugs for the treatment of diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists and inhibitors of dipeptidyl peptidase-4 (DPP-4) have shown pleiotropic effects on bone metabolism and anti-inflammatory properties. The aim of this study is to evaluate the effects of exenatide (GLP-1 agonist) and sitagliptin (DPP-4 inhibitor) during periodontitis induction by ligature insertion in rats.. Forty rats were divided into four groups: 1) animals with induced periodontitis that received exenatide (EG); 2) animals with induced periodontitis that received sitagliptin (SG); 3) animals with induced periodontitis and without drug treatment (LG); and 4) animals without induced periodontitis and without drug treatment (controls). The drugs were administered for 28 days. On the day the animals were sacrificed, blood was collected for analysis of glucose and DPP-4 levels. The gene expressions of prostaglandin-endoperoxide synthase 2, tissue inhibitor of metalloproteinase 1, Dpp4, nitric oxide synthase 2 (Nos2), interleukin 1β (Il1b), and matrix metalloproteinase 9 (Mmp9) in the gingiva; support and alveolar bone loss; connective tissue attachment; and the quantity of gingival collagen were evaluated.. Exenatide and sitagliptin treatments have led to a lower percentage of weight gain but did not influence glycemia. Sitagliptin reduced the serum concentration of DPP-4. Interestingly, although the gene expression profile has revealed a downregulation of Mmp9, Nos2, and Il1b in both EG and SG compared to LG, a significant protective effect was not observed on alveolar bone and collagen tissue in this model.. Regardless of the reduction of the expression of Il1b, Nos2, and Mmp9, the drugs were not effective in the stabilization or reduction of alveolar bone loss and collagen degradation in rats.

Topics: Alveolar Bone Loss; Animals; Exenatide; Hypoglycemic Agents; Interleukin-1beta; Matrix Metalloproteinase 9; Nitric Oxide Synthase Type II; Peptides; Periodontitis; Rats; Sitagliptin Phosphate; Tissue Inhibitor of Metalloproteinase-1; Venoms