Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway
Background/purpose: Glycogen synthase kinase-3β (GSK3β) inhibitor enhances bone formation, while dental pulp stem cells (DPSC) are potentially used to repair bone defects. The present study aimed to investigate the effect of AR-A014418 (AR, a specific glycogen synthase kinase-3β inhibitor) on the mi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Journal of Dental Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1991790221002452 |
| _version_ | 1819174065017978880 |
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| author | Huilan Xie Yi Lin Fang Fang |
| author_facet | Huilan Xie Yi Lin Fang Fang |
| author_sort | Huilan Xie |
| collection | DOAJ |
| description | Background/purpose: Glycogen synthase kinase-3β (GSK3β) inhibitor enhances bone formation, while dental pulp stem cells (DPSC) are potentially used to repair bone defects. The present study aimed to investigate the effect of AR-A014418 (AR, a specific glycogen synthase kinase-3β inhibitor) on the migration and osteogenic differentiation of rat-derived dental pulp stem cells (rDPSCs), and further explore the underlying mechanism. Materials and methods: rDPSCs were isolated from rats, and then cultured with different concentrations of AR with or without LY294002 (a PI3K inhibitor). Then, cell viability, migration, osteogenic differentiation, and the involvement of PI3K pathway were detected by CCK-8 assay, Transwell assay, Alizarin Red S Staining, Alkaline phosphatase (ALP) assay, Western blot, and RT-PCR, respectively. Results: Our present study demonstrated that AR of various concentrations (1 μM, 2.5 μM, and 5 μM) not only promoted the rDPSC proliferation and migration, but also increased calcium deposition, the activity of alkaline phosphatase (ALP), and levels of osteogenic markers (RUNX2, OPN, OCN, and OSX) in rDPSCs. It was also found that the administration of AR resulted in an increase in the expression level of p-GSK3β (Ser), β-catenin, p-PI3K, and p-Akt, and a reduction in p-GSK3β (Tyr216). Furthermore, PI3K inhibitor LY294002 abrogated the enhanced cell migration and osteogenic differentiation of rDPSCs induced by AR. Conclusion: Our results provide evidence that AR significantly promotes migration and osteogenic differentiation of rDPSCs by activating β-catenin/PI3K/Akt signaling pathway. |
| first_indexed | 2024-12-22T20:33:02Z |
| format | Article |
| id | doaj.art-6bb8757bf380436a8d4aa26633ad0993 |
| institution | Directory Open Access Journal |
| issn | 1991-7902 |
| language | English |
| last_indexed | 2024-12-22T20:33:02Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Dental Sciences |
| spelling | doaj.art-6bb8757bf380436a8d4aa26633ad09932022-12-21T18:13:33ZengElsevierJournal of Dental Sciences1991-79022022-04-01172802810Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathwayHuilan Xie0Yi Lin1Fang Fang2Corresponding author. Department of Stomatology, Fujian Provincial Hospital, No. 134, East Street, Gulou District, Fuzhou, 350001, Fujian, China.; Department of Stomatology, Fujian Provincial Hospital, Fuzhou, Fujian, ChinaDepartment of Stomatology, Fujian Provincial Hospital, Fuzhou, Fujian, ChinaDepartment of Stomatology, Fujian Provincial Hospital, Fuzhou, Fujian, ChinaBackground/purpose: Glycogen synthase kinase-3β (GSK3β) inhibitor enhances bone formation, while dental pulp stem cells (DPSC) are potentially used to repair bone defects. The present study aimed to investigate the effect of AR-A014418 (AR, a specific glycogen synthase kinase-3β inhibitor) on the migration and osteogenic differentiation of rat-derived dental pulp stem cells (rDPSCs), and further explore the underlying mechanism. Materials and methods: rDPSCs were isolated from rats, and then cultured with different concentrations of AR with or without LY294002 (a PI3K inhibitor). Then, cell viability, migration, osteogenic differentiation, and the involvement of PI3K pathway were detected by CCK-8 assay, Transwell assay, Alizarin Red S Staining, Alkaline phosphatase (ALP) assay, Western blot, and RT-PCR, respectively. Results: Our present study demonstrated that AR of various concentrations (1 μM, 2.5 μM, and 5 μM) not only promoted the rDPSC proliferation and migration, but also increased calcium deposition, the activity of alkaline phosphatase (ALP), and levels of osteogenic markers (RUNX2, OPN, OCN, and OSX) in rDPSCs. It was also found that the administration of AR resulted in an increase in the expression level of p-GSK3β (Ser), β-catenin, p-PI3K, and p-Akt, and a reduction in p-GSK3β (Tyr216). Furthermore, PI3K inhibitor LY294002 abrogated the enhanced cell migration and osteogenic differentiation of rDPSCs induced by AR. Conclusion: Our results provide evidence that AR significantly promotes migration and osteogenic differentiation of rDPSCs by activating β-catenin/PI3K/Akt signaling pathway.http://www.sciencedirect.com/science/article/pii/S1991790221002452Glycogen synthase kinase-3β inhibitorDental pulp stem cellsMigrationOsteogenic differentiationPI3K |
| spellingShingle | Huilan Xie Yi Lin Fang Fang Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway Journal of Dental Sciences Glycogen synthase kinase-3β inhibitor Dental pulp stem cells Migration Osteogenic differentiation PI3K |
| title | Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway |
| title_full | Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway |
| title_fullStr | Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway |
| title_full_unstemmed | Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway |
| title_short | Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway |
| title_sort | glycogen synthase kinase 3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β catenin pi3k akt signaling pathway |
| topic | Glycogen synthase kinase-3β inhibitor Dental pulp stem cells Migration Osteogenic differentiation PI3K |
| url | http://www.sciencedirect.com/science/article/pii/S1991790221002452 |
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