Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways
Abstract Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic d...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-04-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-022-00173-5 |
| _version_ | 1828347490303213568 |
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| author | Bongkun Choi Ji-Eun Kim Si-On Park Eun-Young Kim Soyoon Oh Hyuksu Choi Dohee Yoon Hyo-Jin Min Hyung-Ryong Kim Eun-Ju Chang |
| author_facet | Bongkun Choi Ji-Eun Kim Si-On Park Eun-Young Kim Soyoon Oh Hyuksu Choi Dohee Yoon Hyo-Jin Min Hyung-Ryong Kim Eun-Ju Chang |
| author_sort | Bongkun Choi |
| collection | DOAJ |
| description | Abstract Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics. |
| first_indexed | 2024-04-14T00:40:36Z |
| format | Article |
| id | doaj.art-84f9e2108aef44f99a50fa22984154bb |
| institution | Directory Open Access Journal |
| issn | 1674-2818 2049-3169 |
| language | English |
| last_indexed | 2024-04-14T00:40:36Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj.art-84f9e2108aef44f99a50fa22984154bb2022-12-22T02:22:11ZengNature Publishing GroupInternational Journal of Oral Science1674-28182049-31692022-04-011411910.1038/s41368-022-00173-5Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathwaysBongkun Choi0Ji-Eun Kim1Si-On Park2Eun-Young Kim3Soyoon Oh4Hyuksu Choi5Dohee Yoon6Hyo-Jin Min7Hyung-Ryong Kim8Eun-Ju Chang9Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Pharmacology, College of Dentistry, Jeonbuk National UniversityDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of MedicineAbstract Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.https://doi.org/10.1038/s41368-022-00173-5 |
| spellingShingle | Bongkun Choi Ji-Eun Kim Si-On Park Eun-Young Kim Soyoon Oh Hyuksu Choi Dohee Yoon Hyo-Jin Min Hyung-Ryong Kim Eun-Ju Chang Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways International Journal of Oral Science |
| title | Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways |
| title_full | Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways |
| title_fullStr | Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways |
| title_full_unstemmed | Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways |
| title_short | Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways |
| title_sort | sphingosine 1 phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with akt signaling pathways |
| url | https://doi.org/10.1038/s41368-022-00173-5 |
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