Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, People's Republic of China.
Stem Cells. 2024 Feb 8;42(2):116-127. doi: 10.1093/stmcls/sxad083.
Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.
人牙髓干细胞（hDPSCs）在牙髓病后牙髓-牙本质复合体的再生中起着至关重要的作用。虽然再生效率依赖于 hDPSCs 的成牙本质细胞分化能力，但在牙髓腔内很难调节。尽管烟酰胺核糖（NR）已被发现可促进组织再生，但它在牙髓-牙本质复合体再生中的具体作用尚未完全了解。在这里，我们旨在探讨 NR 在 hDPSCs 成牙本质细胞分化中的作用及其潜在的分子机制。结果发现，NR 通过提高 NAD+/NADH 水平来增强 hDPSCs 的活力并延缓衰老。与 NR 的持续作用相反，NR 预处理增强了 hDPSCs 的多向分化。此外，在裸鼠异位牙髓再生实验中，NR 预处理的 hDPSCs 移植可促进由细胞阳性表达 DMP-1 和 DSPP 所包围的牙本质样结构的形成。RNA-Seq 显示 NR 预处理抑制了 hDPSCs 中的 HIF-1 信号通路。NR 预处理的 hDPSCs 中 HIF-1α 阳性细胞的数量明显减少。同样，NR 也显著下调了体外 hDPSCs 中 HIF-1α 的表达。这些发现表明，NR 可能调节 hDPSC 成牙本质细胞分化并促进创新的牙髓修复策略的发展。
