Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Division of Oral Science for Health Promotion, Department of Oral Health and Welfare, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Sci Rep. 2023 Jan 23;13(1):1251. doi: 10.1038/s41598-023-28197-9.
Ascorbic acid (AA; vitamin C) plays a crucial role in the biosynthesis and secretion of collagen to produce the organic matrix of hard tissues. Nevertheless, the detailed mechanism by which AA induces reparative dentinogenesis is still unknown. This study aimed to investigate the pathway and function of AA during wound healing in a rat pulpotomy model. Sodium-dependent vitamin C transporter (SVCT) 2 and glucose transporter (GLUT) 1 were detected in odontoblasts, endothelial cells, and nerve fibers in normal pulp tissues. SVCT2 and GLUT1 were also expressed in odontoblast-like cells in pulpotomized tissues of Wistar rats, and immunopositive cells of SVCT2 were significantly increased at 5 days after pulpotomy (p < 0.05). By contrast, osteogenic disorder Shionogi (ODS) rats, which cannot generate AA, also expressed SVCT2 and GLUT1 in normal and wound healing conditions. However, in ODS rats, when compared with the AA-addition group, the formation of dentin bridges in the AA-loss group was not evident, a layer of osteopontin was significantly increased beneath the wound surface (p < 0.05), and alpha smooth muscle actin at the odontoblast-like cells observed along this layer was significantly increased (p < 0.05), but not Nestin. Moreover, the amounts of type 1 collagen generated in the reparative dentin and beneath the wound healing site were significantly diminished (p < 0.05). Macrophages expressing CD68 and CD206 increased beneath the wound site. Hence, AA may be involved in odontoblast-like cell differentiation and anti-inflammatory response during dental pulp wound healing. Our results provide new insights into the function of AA through SVCT2 and GLUT1 in reparative dentinogenesis and may help in developing new therapeutic targets for dental pulpal disease.
抗坏血酸（AA；维生素 C）在胶原蛋白的生物合成和分泌中发挥着至关重要的作用，以产生硬组织的有机基质。然而，AA 诱导修复性牙本质形成的详细机制尚不清楚。本研究旨在通过大鼠盖髓模型研究 AA 在创伤愈合过程中的途径和功能。钠依赖性维生素 C 转运体（SVCT）2 和葡萄糖转运体（GLUT）1 在正常牙髓组织的成牙本质细胞、内皮细胞和神经纤维中被检测到。SVCT2 和 GLUT1 也在 Wistar 大鼠盖髓组织的成牙本质样细胞中表达，SVCT2 免疫阳性细胞在盖髓后 5 天显著增加（p<0.05）。相比之下，不能产生 AA 的 Shionogi 骨病（ODS）大鼠在正常和创伤愈合条件下也表达 SVCT2 和 GLUT1。然而，在 ODS 大鼠中，与 AA 添加组相比，AA 缺失组牙本质桥的形成不明显，在创面下明显增加了一层骨桥蛋白（p<0.05），并且沿着该层观察到的成牙本质样细胞中的α平滑肌肌动蛋白显著增加（p<0.05），但巢蛋白没有增加。此外，在修复性牙本质和创伤愈合部位下方产生的 I 型胶原的量明显减少（p<0.05）。在创面下表达 CD68 和 CD206 的巨噬细胞增加。因此，AA 可能参与牙髓创伤愈合过程中成牙本质样细胞的分化和抗炎反应。我们的结果通过 SVCT2 和 GLUT1 提供了 AA 在修复性牙本质形成中的功能的新见解，并可能有助于为牙髓疾病开发新的治疗靶点。
