State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, People's Republic of China.
Department of Stomatology, No.969 Hospital, Joint Logistics Support Force of the Chinese People's Liberation Army, Hohhot, Inner Mongolia, 010000, People's Republic of China.
Stem Cell Rev Rep. 2024 May;20(4):1060-1077. doi: 10.1007/s12015-024-10695-6. Epub 2024 Feb 28.
Dental pulp regeneration therapy is a challenge to achieve early vascularization during treatment. Studying the regulatory mechanisms of vascular formation during human dental pulp development may provide insights for related therapies. In this study, we utilized single-cell sequencing analysis to compare the gene expression of dental pulp stem cells (DPSCs) and vascular endothelial cells (ECs) from developing and mature dental pulps.
Immunohistochemistry, Western blot, and real-time polymerase chain reaction (RT-PCR) were used to detect fibronectin 1 (FN1) expression and molecules, such as PI3K/AKT. Cell proliferation assay, scratch assay, tube formation assay and were used to investigate the effects of DPSCs on the vasculogenetic capability of ECs. Additionally, animal experiments involving mice were conducted.
The results revealed that DPSCs exist around dental pulp vasculature. FN1 expression was significantly higher in DPSCs from young permanent pulps than mature pulps, promoting HUVEC proliferation, migration, and tube formation via ITGA5 and the downstream PI3K/AKT signaling pathway.
Our data indicate that intercellular communication between DPSCs and ECs mediated by FN1-ITGA5 signaling is crucial for vascularizationduring dental pulp development, laying an experimental foundation for future clinical studies.
牙髓再生治疗的一个挑战是在治疗过程中实现早期血管化。研究人牙髓发育过程中血管形成的调控机制，可能为相关治疗提供思路。本研究利用单细胞测序分析比较了来自发育中和成熟牙髓的牙髓干细胞（DPSC）和血管内皮细胞（EC）的基因表达。
免疫组织化学、Western blot 和实时聚合酶链反应（RT-PCR）用于检测纤连蛋白 1（FN1）表达和 PI3K/AKT 等分子。细胞增殖试验、划痕试验、管形成试验用于研究 DPSC 对 EC 血管生成能力的影响。此外，还进行了涉及小鼠的动物实验。
结果表明 DPSC 存在于牙髓血管周围。年轻恒牙牙髓中的 DPSC 的 FN1 表达明显高于成熟牙髓，通过 ITGA5 和下游的 PI3K/AKT 信号通路促进 HUVEC 的增殖、迁移和管形成。
我们的数据表明，FN1-ITGA5 信号介导的 DPSC 和 EC 之间的细胞间通讯对于牙髓发育过程中的血管化至关重要，为未来的临床研究奠定了实验基础。
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