Affiliated Stomatological Hospital of Xuzhou Medical University, No. 130 Huaihai West Road, Xuzhou, 221000, Jiangsu, China.
Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, 999077, China.
Stem Cell Res Ther. 2020 Jan 29;11(1):40. doi: 10.1186/s13287-019-1540-2.
Alveolar bone loss is a frequent occurrence. Dental pulp stem cells (DPSCs) which have invasive accessibility and high osteogenic potential is a promising source for cell-based bone regeneration. EphrinB2 is involved in bone homeostasis and osteogenesis. The aim of this study was to investigate the effect and mechanism of ephrinB2 overexpression on osteogenic differentiation of DPSCs and bone defect repair.
EphrinB2 expression was analyzed during osteogenic induction of human DPSCs (hDPSCs). Endogenous ephrinB2 expression in hDPSCs was then upregulated using EfnB2 lentiviral vectors. The effect of ephrinB2 overexpression on osteogenic differentiation capacity of hDPSCs was investigated in vitro, and activation of ephrinB2-EphB4 bidirectional signaling in ephrinB2-overexpressing hDPSCs was detected. In vivo, a canine alveolar bone defect model was established and canine DPSCs (cDPSCs) were cultured, characterized, EfnB2-tranfected, and combined with a PuraMatrix scaffold. Micro-CT analysis was performed to evaluate the therapeutic effect of ephrinB2-overexpressing cDPSCs on bone defect repair.
EphrinB2 was upregulated after osteogenic induction of hDPSCs. EphrinB2 overexpression enhanced osteogenic differentiation capacity of hDPSCs in vitro. Moreover, p-ephrinB2 instead of p-EphB4 was upregulated by ephrinB2 overexpression, and activation of ephrinB2-mediated reverse signaling promoted osteogenic differentiation of hDPSCs. In a canine bone defect model, ephrinB2 overexpression in cDPSCs significantly improved trabecular bone volume per tissue volume (BV/TV) and trabecular thickness, as demonstrated by radiographic analysis.
EphrinB2 overexpression enhanced osteogenic potential of DPSCs partially via upregulation of ephrinB2-mediated reverse signaling and effectively promoted alveolar bone defect repair.
牙槽骨丧失是一种常见现象。牙髓干细胞（DPSCs）具有侵袭性和高成骨潜能，是细胞骨再生的有前途的来源。EphrinB2 参与骨稳态和成骨作用。本研究旨在探讨 EphrinB2 过表达对 DPSCs 成骨分化和骨缺损修复的影响及其机制。
分析人牙髓干细胞（hDPSCs）成骨诱导过程中 EphrinB2 的表达。使用 EfnB2 慢病毒载体上调 hDPSCs 中内源性 EphrinB2 的表达。体外研究 EphrinB2 过表达对 hDPSCs 成骨分化能力的影响，并检测 EphrinB2 过表达 hDPSCs 中 EphrinB2-EphB4 双向信号的激活。体内，建立犬牙槽骨缺损模型，培养犬牙髓干细胞（cDPSCs），转染 EfnB2，与 PuraMatrix 支架结合。进行微 CT 分析以评估 EphrinB2 过表达 cDPSCs 对骨缺损修复的治疗效果。
hDPSCs 成骨诱导后 EphrinB2 上调。EphrinB2 过表达增强了 hDPSCs 的体外成骨分化能力。此外，EphrinB2 过表达上调了 p-ephrinB2 而不是 p-EphB4，EphrinB2 介导的反向信号的激活促进了 hDPSCs 的成骨分化。在犬骨缺损模型中，cDPSCs 中的 EphrinB2 过表达通过放射分析显示明显提高了组织体积中的小梁骨体积比（BV/TV）和小梁厚度。
EphrinB2 过表达通过上调 EphrinB2 介导的反向信号部分增强了 DPSCs 的成骨潜能，并有效促进了牙槽骨缺损修复。
