Exendin-4 Relieves the Inhibitory Effects of High Glucose on the Proliferation and Osteoblastic Differentiation of Periodontal Ligament Stem Cells

Publication date: Available online 27 March 2018
Source:Archives of Oral Biology
Author(s): Zijun Guo, Rui Chen, Fujun Zhang, Ming Ding, Ping Wang
BackgroundWith 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.MethodsPDLSCs 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).ResultsThe 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 was significantly reversed, the HG-increased ROS level could be down-regulated. Moreover, Ex-4 enhanced the osteogenic differentiation of normal PDLSCs.ConclusionsEx-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.



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