Hu Meijun, Fan Zhipeng
Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China.
Int J Oral Sci. 2025 Mar 26;17(1):24. doi: 10.1038/s41368-025-00353-z.
Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability. The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques. These methods can influence the cellular microenvironment, activate disparate signaling pathways, and induce different biological effects. "Epigenetic regulation" refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages. The most important sites of histone methylation in tooth organization were found to be H3K4, H3K9, and H3K27. Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications. A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation. Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4, H3K9, and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments. This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
牙间充质干细胞（DMSCs）对于牙齿发育和牙周组织健康至关重要，由于其多向分化潜能和自我更新能力，在组织工程和再生医学中发挥着重要作用。细胞微环境调节干细胞的命运，并且可以使用各种优化技术进行修饰。这些方法可以影响细胞微环境，激活不同的信号通路，并诱导不同的生物学效应。“表观遗传调控”是指在不改变DNA序列的情况下影响基因表达和调节细胞命运的过程，例如组蛋白甲基化。组蛋白甲基化修饰调节控制DMSCs向成骨/牙源性谱系分化的关键转录因子。发现在牙齿组织中组蛋白甲基化的最重要位点是H3K4、H3K9和H3K27。组蛋白甲基化通过在主要三甲基化位点之间维持微妙的平衡来影响基因表达并调节干细胞分化，产生与特定下游转录状态相关的不同染色质结构。与成骨分化相关的几个关键信号通路易受组蛋白甲基化修饰的调节。深入了解控制DMSCs成骨/牙源性分化和免疫炎症反应中组蛋白甲基化修饰的调控机制，将有助于进一步研究DMSC介导的组织再生和炎症中组蛋白甲基化的表观遗传调控。以下是对H3K4、H3K9和H3K27位点的表观遗传组蛋白甲基化在非炎症和炎症微环境中调节DMSCs成骨/牙源性分化和更新的关键功能的简要概述。本综述总结了在组织再生和治疗干预背景下对这些过程的当前研究。
