Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
Diabetes mellitus (DM) increases the destruction of periodontal tissue and impairs osteogenesis differentiation. Exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analogue, can be used for treating DM and promotes bone regeneration. The aim of this study was to explore the effect and mechanism of...
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| Format: | Article |
| Language: | English |
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De Gruyter
2023-04-01
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| Series: | Open Medicine |
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| Online Access: | https://doi.org/10.1515/med-2023-0692 |
| _version_ | 1797832503827890176 |
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| author | Wang Min Liu Min Zheng Jiawen Xiong Li Wang Ping |
| author_facet | Wang Min Liu Min Zheng Jiawen Xiong Li Wang Ping |
| author_sort | Wang Min |
| collection | DOAJ |
| description | Diabetes mellitus (DM) increases the destruction of periodontal tissue and impairs osteogenesis differentiation. Exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analogue, can be used for treating DM and promotes bone regeneration. The aim of this study was to explore the effect and mechanism of Ex-4 on improving the osteogenesis of periodontal ligament stem cells (PDLSCs) in a high glucose environment. Alkaline phosphatase staining and alizarin red staining were used to detect the osteogenic differentiation of PDLSCs. The results showed that 10 nM Ex-4 could reduce the osteogenesis inhibition of PDLSCs induced by high glucose. RT-PCR and western blot results showed that Ex-4 increased the osteogenesis-related gene expression of ALP, Runx2, and Osx, and upregulated the phosphorylation of P38, JNK, and ERK1/2; the peak effect was observed in the range 0.5–1.0 h. Mitogen-activated protein kinase (MAPK) inhibitors PD98059, SB203580, and SP600125 blocked the effects of Ex-4 on MAPK activation and decreased the expression of ALP, Runx2, and Osx in PDLSCs. Moreover, after Ex-4 treatment, the total β-catenin, p-GSK3β, LEF, and Runx2 protein levels increased under normal or high glucose environments. In conclusion, our results indicated that Ex-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of PDLSCs in a high glucose environment. |
| first_indexed | 2024-04-09T14:10:02Z |
| format | Article |
| id | doaj.art-92d4d237a54a4cbebb93f177de3181ed |
| institution | Directory Open Access Journal |
| issn | 2391-5463 |
| language | English |
| last_indexed | 2024-04-09T14:10:02Z |
| publishDate | 2023-04-01 |
| publisher | De Gruyter |
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| series | Open Medicine |
| spelling | doaj.art-92d4d237a54a4cbebb93f177de3181ed2023-05-06T15:31:53ZengDe GruyterOpen Medicine2391-54632023-04-01181170382010.1515/med-2023-0692Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environmentWang Min0Liu Min1Zheng Jiawen2Xiong Li3Wang Ping4Department of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Stomatology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400016, ChinaDiabetes mellitus (DM) increases the destruction of periodontal tissue and impairs osteogenesis differentiation. Exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analogue, can be used for treating DM and promotes bone regeneration. The aim of this study was to explore the effect and mechanism of Ex-4 on improving the osteogenesis of periodontal ligament stem cells (PDLSCs) in a high glucose environment. Alkaline phosphatase staining and alizarin red staining were used to detect the osteogenic differentiation of PDLSCs. The results showed that 10 nM Ex-4 could reduce the osteogenesis inhibition of PDLSCs induced by high glucose. RT-PCR and western blot results showed that Ex-4 increased the osteogenesis-related gene expression of ALP, Runx2, and Osx, and upregulated the phosphorylation of P38, JNK, and ERK1/2; the peak effect was observed in the range 0.5–1.0 h. Mitogen-activated protein kinase (MAPK) inhibitors PD98059, SB203580, and SP600125 blocked the effects of Ex-4 on MAPK activation and decreased the expression of ALP, Runx2, and Osx in PDLSCs. Moreover, after Ex-4 treatment, the total β-catenin, p-GSK3β, LEF, and Runx2 protein levels increased under normal or high glucose environments. In conclusion, our results indicated that Ex-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of PDLSCs in a high glucose environment.https://doi.org/10.1515/med-2023-0692exendin-4osteogenic differentiationpdlscshigh glucosemapk signalingwnt signaling |
| spellingShingle | Wang Min Liu Min Zheng Jiawen Xiong Li Wang Ping Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment Open Medicine exendin-4 osteogenic differentiation pdlscs high glucose mapk signaling wnt signaling |
| title | Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment |
| title_full | Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment |
| title_fullStr | Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment |
| title_full_unstemmed | Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment |
| title_short | Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment |
| title_sort | exendin 4 regulates the mapk and wnt signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment |
| topic | exendin-4 osteogenic differentiation pdlscs high glucose mapk signaling wnt signaling |
| url | https://doi.org/10.1515/med-2023-0692 |
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