Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Hangzhou Stomatological Hospital, Hangzhou, China.
J Periodontal Res. 2023 Apr;58(2):444-455. doi: 10.1111/jre.13105. Epub 2023 Feb 2.
To investigate the changes in the m6A methylation modification profile of human periodontal ligament cells (hPDLCs) in response to inflammatory conditions.
Periodontitis is an infectious disease of the periodontal support tissue that leads to the loss of alveolar bone. HPDLCs are primary cells that can repair periodontal tissue defects caused by periodontitis. However, the inflammatory conditions induce inflammatory damage and decrease ossification of hPDLCs. This inflammatory response depends on genetic and epigenetic mechanisms, including m6A methylation.
HPDLCs were cultured with osteogenic induction medium (NC group), while TNF-α (10 ng/mL) and IL-1β (5 ng/mL) were added to simulate inflammatory conditions (Inflam group). Then RNA-seq and MeRIP-seq analyses were performed to identify m6A methylation modification in the transcriptome range of hPDLCs.
The results showed that the osteogenic differentiation of hPDLCs was inhibited under inflammatory conditions. RNA-seq analysis also revealed that the decreased genes in response to inflammatory conditions were primarily annotated in processes associated with ossification. Compared with the NC group, differentially m6A-methylated genes were primarily enriched in histone modification processes. Among 145 histone modification genes, 25 genes have been reported to be involved in the regulation of osteogenic differentiation, and they include KAT6B, EP300, BMI1, and KDMs (KDM1A, KDM2A, KDM3A, KDM4B, and KDM5A).
This study demonstrated that the m6A landscape of hPDLCs was changed in response to inflammation. M6A methylation differences among histone modification genes may act on the osteogenic differentiation of hPDLCs.
研究人牙周膜细胞（hPDLCs）在炎症条件下 m6A 甲基化修饰谱的变化。
牙周炎是一种感染性牙周支持组织疾病，可导致牙槽骨丧失。hPDLCs 是一种主要的细胞，可修复由牙周炎引起的牙周组织缺损。然而，炎症条件会诱导炎症损伤并减少 hPDLCs 的成骨作用。这种炎症反应取决于遗传和表观遗传机制，包括 m6A 甲基化。
用成骨诱导培养基培养 hPDLCs（NC 组），同时加入 TNF-α（10ng/mL）和 IL-1β（5ng/mL）模拟炎症条件（Inflam 组）。然后进行 RNA-seq 和 MeRIP-seq 分析，以鉴定 hPDLCs 转录组范围内的 m6A 甲基化修饰。
结果表明，炎症条件下 hPDLCs 的成骨分化受到抑制。RNA-seq 分析还表明，对炎症条件反应降低的基因主要注释在与成骨相关的过程中。与 NC 组相比，差异 m6A 甲基化基因主要富集在组蛋白修饰过程中。在 145 个组蛋白修饰基因中，有 25 个基因已被报道参与成骨分化的调节，其中包括 KAT6B、EP300、BMI1 和 KDMs（KDM1A、KDM2A、KDM3A、KDM4B 和 KDM5A）。
本研究表明，hPDLCs 的 m6A 图谱在炎症反应中发生改变。组蛋白修饰基因之间的 m6A 甲基化差异可能作用于 hPDLCs 的成骨分化。
