单位：[1]Department ofOrthodontics, School and Hospital of Stomatology, Shandong University&Shandong Provincial Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, China[2]Department of Stomatology, Linyi People's Hospital, Linyi, Shandong Province, China[3]Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Shandong University & Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, China[4]Department of Orthodontics, Faculty of Stomatology, Liaocheng People's Hospital of Shandong Province, Liaocheng, Shandong Province, China[5]Dental Medical Center, China–Japan Friendship Hospital, Beijing 100029, China
Background and objective: Advanced glycation end products (AGEs) have been hypothesized as the etiologic factors of diabetic periodontitis. The discovery of incretins (including GLP-1 and GIP) provides a novel therapy for the treatment of diabetes. Recent reports have shown that glucagon-like peptide-1 (GLP-1) is an important modulator of bone growth and remodeling. The aim of this study was to clarify the mechanism of how GLP-1 weakens/inhibits the effect of AGEs in hPDLSCs (human periodontal ligament stem cells). Materials and methods: The hPDLSCs were cultured under simulated conditions of osteogenic culture, AGES, AGEs + GLP-1, AGEs + GLP-1 + PMA and AGEs + GLP-1 + LY333531. The phenomenon and related mechanism of cell osteogenesis under different microenvironments were evaluated by Alizarin red staining, ALP staining and quantitative activity measurement, RT-qPCR, western blotting and immunofluorescence staining. Results: RT-qPCR showed that AGEs negatively regulated the expression of osteogenic differentiation markers (ALP, BSP, OPN, and Runx2); in contrast, GLP-1 increased the expression of these markers. Furthermore, the expression of RAGE and pPKC beta (PKC phosphorylation) in the AGE group was upregulated, while the expression of RAGE and pPKC beta was decreased in the GLP-1 group compared with the AGE group. Conclusions: AGES impaired the osteogenic potential of hPDLSCs via PKC beta 2. Our phenomenon showed that GLP-1 could reverse the function of AGEs on osteogenic potential. In addition, the mechanism of GLP-1 weakens/inhibits the effect of AGEs in hPDLSCs, possibly by inhibiting PKC beta 2 phosphorylation. (C) 2019 Elsevier Inc. All rights reserved.
基金：
Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81371180]; International Scientific and Technological Cooperation and Exchange [2014DFA31520]
第一作者单位：[1]Department ofOrthodontics, School and Hospital of Stomatology, Shandong University&Shandong Provincial Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, China[2]Department of Stomatology, Linyi People's Hospital, Linyi, Shandong Province, China
通讯作者：
通讯机构：[1]Department ofOrthodontics, School and Hospital of Stomatology, Shandong University&Shandong Provincial Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, China[5]Dental Medical Center, China–Japan Friendship Hospital, Beijing 100029, China[*1]No. 44-1, Wenhua Road West, Jinan city, Shandong province 250012, China
推荐引用方式(GB/T 7714)：
Wang Zhi,Wang Xuxia,Zhang Lina,et al.GLP-1 inhibits PKC beta 2 phosphorylation to improve the osteogenic differentiation potential of hPDLSCs in the AGE microenvironment[J].JOURNAL of DIABETES and ITS COMPLICATIONS.2020,34(3):doi:10.1016/j.jdiacomp.2019.107495.
APA：
Wang, Zhi,Wang, Xuxia,Zhang, Lina,Wang, Baoliang,Xu, Baohua&Zhang, Jun.(2020).GLP-1 inhibits PKC beta 2 phosphorylation to improve the osteogenic differentiation potential of hPDLSCs in the AGE microenvironment.JOURNAL of DIABETES and ITS COMPLICATIONS,34,(3)
MLA：
Wang, Zhi,et al."GLP-1 inhibits PKC beta 2 phosphorylation to improve the osteogenic differentiation potential of hPDLSCs in the AGE microenvironment".JOURNAL of DIABETES and ITS COMPLICATIONS 34..3(2020)
