Ni Zihan, Cai Luhui, Tsai I-Chen, Ding Wenqian, Tian Cheng, Li Di, Xu Qiong
Hospital of Stomatology, Sun Yat-sen University, 56# Lingyuan West Road, Guangzhou 510055, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.
Int J Mol Sci. 2025 May 2;26(9):4325. doi: 10.3390/ijms26094325.
Severe dental pulp inflammation can lead to tissue lysis and destruction, underscoring the necessity for effective treatment of pulpitis. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (acC) modification has recently emerged as a key regulator in inflammatory processes. However, whether NAT10 affects the inflammatory response in human dental pulp stem cells (hDPSCs) remains unelucidated. In this study, elevated NAT10 expression was observed in pulpitis tissues and LPS-stimulated hDPSCs. Knockdown of NAT10 led to reduced inflammatory gene expression and lower reactive oxygen species (ROS) production in LPS-stimulated hDPSCs, while the chemotactic migration of macrophages was also suppressed. Similar results were observed when hDPSCs were treated with Remodelin, an inhibitor of NAT10. Differentially expressed genes identified through RNA sequencing were significantly enriched in inflammatory signaling pathways after NAT10 depletion. Among the differential genes, pentraxins 3 (PTX3) was identified as the potential target gene due to the presence of the acC modification site and its known ability to regulate dental pulp inflammation. The mRNA and protein levels of PTX3 were reduced in NAT10-deficient cells, along with a decrease in its mRNA stability. Exogenous PTX3 supplementation partially reversed the inflammatory inhibition induced by NAT10 knockdown. Further evidence in vivo revealed that Remodelin treatment attenuated the severity of dental pulp inflammation in rats with pulpitis. In summary, these data indicated that NAT10 deficiency inhibited the stability of PTX3 mRNA and further inhibited hDPSC inflammation, while Remodelin might be a potential therapeutic agent for pulp capping.
严重的牙髓炎症可导致组织溶解和破坏，凸显了有效治疗牙髓炎的必要性。N-乙酰转移酶10（NAT10）介导的N4-乙酰胞苷（acC）修饰最近已成为炎症过程中的关键调节因子。然而，NAT10是否影响人牙髓干细胞（hDPSC）的炎症反应仍不清楚。在本研究中，在牙髓炎组织和脂多糖（LPS）刺激的hDPSC中观察到NAT10表达升高。敲低NAT10导致LPS刺激的hDPSC中炎症基因表达降低和活性氧（ROS）产生减少，同时巨噬细胞的趋化迁移也受到抑制。当用NAT10抑制剂Remodelin处理hDPSC时，观察到类似的结果。通过RNA测序鉴定的差异表达基因在NAT10缺失后显著富集于炎症信号通路中。在差异基因中，由于存在acC修饰位点及其调节牙髓炎症的已知能力，五聚素3（PTX3）被确定为潜在的靶基因。PTX3的mRNA和蛋白水平在NAT10缺陷细胞中降低，同时其mRNA稳定性也降低。外源性补充PTX3部分逆转了NAT10敲低诱导的炎症抑制。体内进一步的证据表明，Remodelin治疗减轻了牙髓炎大鼠牙髓炎症的严重程度。总之，这些数据表明，NAT10缺陷抑制了PTX3 mRNA的稳定性，并进一步抑制了hDPSC炎症，而Remodelin可能是一种潜在的盖髓治疗剂。
