Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Sciences, Kyushu University Graduate School of Dental Science, Fukuoka, Japan.
Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Sci Rep. 2018 Feb 21;8(1):3419. doi: 10.1038/s41598-018-21183-6.
Nitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp tissues under both physiological and pathological conditions. However, little is known about the NO functions in dental pulp stem cells (DPSCs). We examined the direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the odontogenic capacity of rat DPSCs (rDPSCs). In the presence of NOC-18, rDPSCs were transformed into odontoblast-like cells with long cytoplasmic processes and a polarized nucleus. NOC-18 treatment increased alkaline phosphatase activity and enhanced dentin-like mineralized tissue formation and the expression levels of several odontoblast-specific genes, such as runt related factor 2, dentin matrix protein 1 and dentin sialophosphoprotein, in rDPSCs. In contrast, carboxy-PTIO, a NO scavenger, completely suppressed the odontogenic capacity of rDPSCs. This NO-promoted odontogenic differentiation was activated by tumor necrosis factor-NF-κB axis in rDPSCs. Further in vivo study demonstrated that NOC-18-application in a tooth cavity accelerated tertiary dentin formation, which was associated with early nitrotyrosine expression in the dental pulp tissues beneath the cavity. Taken together, the present findings indicate that exogenous NO directly induces the odontogenic capacity of rDPSCs, suggesting that NO donors might offer a novel host DPSC-targeting alternative to current pulp capping agents in endodontics.
一氧化氮（NO）被认为在生理和病理条件下在牙髓组织中发挥关键的调节作用。然而，对于牙髓干细胞（DPSCs）中的 NO 功能知之甚少。我们研究了自发释放 NO 气体供体 NOC-18 对大鼠 DPSCs（rDPSCs）成牙本质能力的直接作用。在 NOC-18 的存在下，rDPSCs 被转化为具有长细胞质突起和极化核的成牙本质细胞样细胞。NOC-18 处理增加碱性磷酸酶活性，并增强牙本质样矿化组织形成和几种成牙本质细胞特异性基因的表达水平，如 runt 相关因子 2、牙本质基质蛋白 1 和牙本质涎磷蛋白在 rDPSCs 中。相比之下，NO 清除剂羧基-PTIO 完全抑制了 rDPSCs 的成牙本质能力。这种 NO 促进的成牙本质分化在 rDPSCs 中被肿瘤坏死因子-NF-κB 轴激活。进一步的体内研究表明，NOC-18 在牙腔中的应用加速了第三期牙本质的形成，这与牙腔下方牙髓组织中早期硝基酪氨酸的表达有关。综上所述，这些发现表明外源性 NO 直接诱导 rDPSCs 的成牙本质能力，表明 NO 供体可能为牙髓治疗中的现有牙髓盖髓剂提供一种新的宿主 DPSC 靶向替代方案。
