Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an Axin2Cre-Dox;Ai14 genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato+ cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato+ cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases.

中文翻译：

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RvE1 促进 Axin2+ 细胞再生并减少细菌侵袭。

活体牙髓治疗和根管治疗（RCT）是不可逆牙髓炎的主要治疗方法。虽然这些手术的成功率很高，但它们也有一些局限性。例如，RCT 会导致牙齿冠部三分之一处的显着牙本质被去除，从而增加牙根骨折的风险，从而迫使牙齿被拔除。理想的治疗目标是牙髓再生，这是随机对照试验无法实现的。专门的促消退介质（SPM）因炎症消退而闻名。炎症的消退和组织的恢复或再生是一个动态且连续的过程。SPM不仅具有强大的免疫调节功能，还能有效促进组织稳态和再生。消解素已被证明可以促进牙髓再生。本研究的目的是进一步探讨 Resolvin E1 (RvE1) 治疗在牙髓再生中的细胞靶点以及 RvE1 对感染牙髓的影响。我们在 Axin2Cre-Dox;Ai14 基因定义的小鼠模型中研究了 RvE1 对实验暴露的有或没有微生物感染的牙髓的作用。我们的结果显示，在小鼠直接盖髓后，RvE1 促进 Axin2-tdTomato+ 细胞扩增和成牙本质细胞分化，我们用它来模拟临床中的可逆性牙髓炎病例。在培养的小鼠牙髓干细胞 (mDPSC) 中，RvE1 促进 Axin2-tdTomato+ 细胞增殖和成牙本质细胞分化，并挽救脂多糖刺激后受损的功能。在暴露于口腔环境24小时的感染牙髓中，RvE1抑制了炎症浸润，减少了根管中的细菌侵入，并阻止了根尖周炎的发展，但其再生作用有限。总的来说，RvE1 的局部治疗通过促进表达 Axin2 的细胞增殖和分化来促进牙髓再生。它还调节炎症的消退、降低感染的严重程度并预防根尖周炎，使 RvE1 成为治疗牙髓疾病的新型疗法。