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Sema4D/PlexinB1 promotes endothelial differentiation of dental pulp stem cells via activation of AKT and ERK1/2 signaling |
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| Authors: | Ting Zou Shan Jiang Waruna Lakmal Dissanayaka Boon Chin Heng Jianguang Xu Ting Gong Xiaojing Huang Chengfei Zhang |
| Affiliation: | 1. Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China;2. Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China Department of Endodontics and Operative Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China;3. Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China HKU Shenzhen Institute of Research and Innovation, Shenzhen, China;4. Department of Endodontics and Operative Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China |
| Abstract: | Inducing of dental pulp stem cells (DPSCs) into endothelial cells (ECs) to prevascularize pulp tissue constructs may offer a novel and viable approach for enhancing pulp regeneration. However, there are numerous challenges in current methods for the acquisition of sufficient translational ECs. It was known that Sema4D/PlexinB1 signaling exerts profound effects on enhancing vascular endothelial growth factor (VEGF) secretion and angiogenesis. Whether Sema4D/PlexinB1 could regulate endothelial differentiation of DPSCs is not yet investigated. In this study, when DPSCs were treated with Sema4D (2 μg/mL), ECs-specific (VEGFR1, VEGFR2, CD31, and vWF), and angiogenic genes and proteins were significantly upregulated. The induced ECs exhibited similar endothelial vessel formation ability to that of human umbilical vein endothelial cells (HUVECs). Furthermore, phosphorylation of AKT increased dramatically within 5 minutes (from 0.93 to 21.8), while p-ERK1/2 was moderately elevated (from 0.94 to 2.65). In summary, our results demonstrated that Sema4D/PlexinB1 signaling induces endothelial differentiation of DPSCs. The interactions of Sema4D, VEGF, ANGPTL4, ANG1, and HIF-1α may play a crucial role in mediating the differentiation process. |
| Keywords: | AKT DPSCs endothelial differentiation ERK1/2 Sema4D |