Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Division of Laboratory Animal Resources, Medical University of South Carolina, Charleston, SC 29425, USA.
Int J Mol Sci. 2023 Feb 8;24(4):3401. doi: 10.3390/ijms24043401.
Sphingosine-1-phosphate receptor 2 () is a G protein-coupled receptor that regulates various immune responses. Herein, we report the effects of a 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 . Treatment with JTE013 enhanced vascular endothelial growth factor A (), platelet derived growth factor subunit A (), and growth differentiation factor 15 () 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 , , 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 by JTE013 increased TGFβ/Smad and Akt signaling; enhanced , , and gene expression; and subsequently promoted angiogenesis and alveolar bone regeneration.
鞘氨醇-1-磷酸受体 2() 是一种 G 蛋白偶联受体，可调节各种免疫反应。在此，我们报告了一种 拮抗剂 (JTE013) 对骨再生的影响。用二甲亚砜 (DMSO) 或 JTE013 处理骨髓基质细胞 (BMSCs)，并在有或没有口腔细菌病原体感染的情况下进行处理。JTE013 处理增强了血管内皮生长因子 A()、血小板衍生生长因子亚基 A() 和生长分化因子 15() 的基因表达，并增加了转化生长因子β(TGFβ)/Smad 和 Akt 信号。将 8 周龄雄性 C57BL/6J 小鼠用结扎丝结扎左侧上颌第 2 磨牙 15 天，以诱导炎症性骨丧失。结扎去除后，将小鼠牙周组织每周用稀释的 DMSO 或 JTE013 处理 3 次，持续 3 周。还两次注射 calcein 以测量骨再生。上颌骨组织的 micro-CT 扫描和 calcein 成像显示，与对照相比，JTE013 处理增强了牙槽骨再生。与对照相比，JTE013 还增加了牙周组织中的、、骨钙素和骨形成蛋白-2 基因表达。牙周组织的组织学检查显示，与对照相比，JTE013 促进了牙周组织中的血管生成。我们的研究结果表明，JTE013 通过抑制 增加了 TGFβ/Smad 和 Akt 信号；增强了、和基因表达；并随后促进了血管生成和牙槽骨再生。
