Wu Zhiwu, Yang Hui, Duan Shaoying, Su Qianqian, Cheng Ran, Hu Tao
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People's Republic of China.
School of Stomatology, Zhejiang Chinese Medical University, The Stomatology Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China.
Stem Cells Transl Med. 2025 Jun 25;14(7). doi: 10.1093/stcltm/szaf022.
Appropriate dental pulp repair is based on effective control of inflammation and involves the regeneration of dental pulp nerves, blood vessels (soft tissue), and dentin (hard tissue). Limited evidence has shown how to modulate the uncertainty due to individual variability in dental pulp repair. NRG1, a cytokine modulating nerve injury and repair, was intricately associated with the outcome of pulp repair. Yet, its mobilization in spontaneous pulp repair had individual variability. The study further explored the role of NRG1 during pulp repair as well as an epigenetic way to modulate NRG1 through histone acetylation to enhance pulp repair. Overexpression of NRG1 exhibited the effects of anti-inflammation and integrated regeneration of soft and hard tissue, by inhibiting pro-inflammatory factors IL-1β, IL-8, and promoting the expressions of DSPP, DMP1 (dentin regeneration), and nestin (nerve regeneration). Moreover, restricted H3K9 and H3K27 acetylation correlated with NRG1 expression in pulp repair both temporally and spatially, showing individual variability as well. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, enhanced H3K9ac and H3K27ac, which dramatically activated NRG1, suppressed pulp inflammation, and facilitated soft and hard tissue regeneration. In summary, targeting histone acetylation with HDAC inhibitors may be an effective approach to promote pulp repair by activating NRG1.
适当的牙髓修复基于对炎症的有效控制，涉及牙髓神经、血管（软组织）和牙本质（硬组织）的再生。有限的证据表明如何调节由于牙髓修复中个体差异导致的不确定性。NRG1是一种调节神经损伤和修复的细胞因子，与牙髓修复的结果密切相关。然而，其在自发性牙髓修复中的动员存在个体差异。该研究进一步探讨了NRG1在牙髓修复过程中的作用，以及通过组蛋白乙酰化调节NRG1以增强牙髓修复的表观遗传方式。NRG1的过表达通过抑制促炎因子IL-1β、IL-8，并促进DSPP、DMP1（牙本质再生）和巢蛋白（神经再生）的表达，表现出抗炎和软硬组织整合再生的作用。此外，在牙髓修复中，H3K9和H3K27的乙酰化受限在时间和空间上均与NRG1表达相关，也表现出个体差异。伏立诺他（SAHA）是一种组蛋白去乙酰化酶（HDAC）抑制剂，可增强H3K9ac和H3K27ac，从而显著激活NRG1，抑制牙髓炎症，并促进软硬组织再生。总之，用HDAC抑制剂靶向组蛋白乙酰化可能是通过激活NRG1促进牙髓修复的有效方法。
