Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis
Sphingosine-1-phosphate receptor 2 (<i>S1PR2</i>) is a G protein-coupled receptor that regulates various immune responses. Herein, we report the effects of a <i>S1PR2</i> antagonist (JTE013) on bone regeneration. Murine bone marrow stromal cells (BMSCs) were treated with dime...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3401 |
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| author | William Lory Bridgette Wellslager Chao Sun Özlem Yilmaz Hong Yu |
| author_facet | William Lory Bridgette Wellslager Chao Sun Özlem Yilmaz Hong Yu |
| author_sort | William Lory |
| collection | DOAJ |
| description | Sphingosine-1-phosphate receptor 2 (<i>S1PR2</i>) is a G protein-coupled receptor that regulates various immune responses. Herein, we report the effects of a <i>S1PR2</i> antagonist (JTE013) on bone regeneration. Murine bone marrow stromal cells (BMSCs) were treated with dimethylsulfoxide (DMSO) or JTE013 with or without infection by an oral bacterial pathogen <i>Aggregatibacter actinomycetemcomitans</i>. Treatment with JTE013 enhanced vascular endothelial growth factor A (<i>VEGFA</i>), platelet derived growth factor subunit A (<i>PDGFA</i>), and growth differentiation factor 15 (<i>GDF15</i>) gene expression and increased transforming growth factor beta (TGFβ)/Smad and Akt signaling. Eight-week-old male C57BL/6J mice were challenged with ligatures around the left maxillary 2nd molar for 15 days to induce inflammatory bone loss. After ligature removal, mice were treated with diluted DMSO or JTE013 in the periodontal tissues 3 times per week for 3 weeks. Calcein was also injected twice to measure bone regeneration. Micro-CT scanning of maxillary bone tissues and calcein imaging revealed that treatment with JTE013 enhanced alveolar bone regeneration. JTE013 also increased <i>VEGFA</i>, <i>PDGFA</i>, osteocalcin, and osterix gene expressions in the periodontal tissues compared to control. Histological examination of periodontal tissues revealed that JTE013 promoted angiogenesis in the periodontal tissues compared to control. Our findings support that inhibition of <i>S1PR2</i> by JTE013 increased TGFβ/Smad and Akt signaling; enhanced <i>VEGFA</i>, <i>PDGFA</i>, and <i>GDF15</i> gene expression; and subsequently promoted angiogenesis and alveolar bone regeneration. |
| first_indexed | 2024-03-11T08:42:46Z |
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| language | English |
| last_indexed | 2024-03-11T08:42:46Z |
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| spelling | doaj.art-3b198bad82c54bf1b3bb0dcfb2fcea262023-11-16T20:59:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244340110.3390/ijms24043401Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting AngiogenesisWilliam Lory0Bridgette Wellslager1Chao Sun2Özlem Yilmaz3Hong Yu4Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USADivision of Laboratory Animal Resources, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USASphingosine-1-phosphate receptor 2 (<i>S1PR2</i>) is a G protein-coupled receptor that regulates various immune responses. Herein, we report the effects of a <i>S1PR2</i> antagonist (JTE013) on bone regeneration. Murine bone marrow stromal cells (BMSCs) were treated with dimethylsulfoxide (DMSO) or JTE013 with or without infection by an oral bacterial pathogen <i>Aggregatibacter actinomycetemcomitans</i>. Treatment with JTE013 enhanced vascular endothelial growth factor A (<i>VEGFA</i>), platelet derived growth factor subunit A (<i>PDGFA</i>), and growth differentiation factor 15 (<i>GDF15</i>) gene expression and increased transforming growth factor beta (TGFβ)/Smad and Akt signaling. Eight-week-old male C57BL/6J mice were challenged with ligatures around the left maxillary 2nd molar for 15 days to induce inflammatory bone loss. After ligature removal, mice were treated with diluted DMSO or JTE013 in the periodontal tissues 3 times per week for 3 weeks. Calcein was also injected twice to measure bone regeneration. Micro-CT scanning of maxillary bone tissues and calcein imaging revealed that treatment with JTE013 enhanced alveolar bone regeneration. JTE013 also increased <i>VEGFA</i>, <i>PDGFA</i>, osteocalcin, and osterix gene expressions in the periodontal tissues compared to control. Histological examination of periodontal tissues revealed that JTE013 promoted angiogenesis in the periodontal tissues compared to control. Our findings support that inhibition of <i>S1PR2</i> by JTE013 increased TGFβ/Smad and Akt signaling; enhanced <i>VEGFA</i>, <i>PDGFA</i>, and <i>GDF15</i> gene expression; and subsequently promoted angiogenesis and alveolar bone regeneration.https://www.mdpi.com/1422-0067/24/4/3401<i>S1PR2</i>JTE013<i>VEGF</i><i>PDGF</i><i>GDF15</i>angiogenesis |
| spellingShingle | William Lory Bridgette Wellslager Chao Sun Özlem Yilmaz Hong Yu Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis International Journal of Molecular Sciences <i>S1PR2</i> JTE013 <i>VEGF</i> <i>PDGF</i> <i>GDF15</i> angiogenesis |
| title | Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis |
| title_full | Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis |
| title_fullStr | Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis |
| title_full_unstemmed | Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis |
| title_short | Inhibition of Sphingosine-1-Phosphate Receptor 2 by JTE013 Enhanced Alveolar Bone Regeneration by Promoting Angiogenesis |
| title_sort | inhibition of sphingosine 1 phosphate receptor 2 by jte013 enhanced alveolar bone regeneration by promoting angiogenesis |
| topic | <i>S1PR2</i> JTE013 <i>VEGF</i> <i>PDGF</i> <i>GDF15</i> angiogenesis |
| url | https://www.mdpi.com/1422-0067/24/4/3401 |
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