Periodontitis is the sixth most prevalent diseases around the globe, which is closely related to many systemic diseases and affects general health. As the leading cause of tooth loss, periodontitis is characterized by irreversible alveolar bone loss and activated osteoclastogenic process, which might be closely related to the activated intracellular reactive oxygen species (ROS) in osteoclasts. Here, we demonstrated triggering receptor expressed on myeloid cells 2 (Trem2) as a key regulator of osteoclastogenesis with the regulation of intracellular ROS signals in periodontitis. In the present study, the expression of Trem2 was significantly upregulated in human alveolar bones diagnosed with chronic periodontitis, as assessed by RNA-seq. In the mice model of periodontitis, the alveolar bone resorption was impeded in the presence of the conditional knockout of Trem2 in osteoclasts. Furthermore, we identified Trem2/DAP12/Syk-dependent cascade as a vital intracellular signaling for the amplification of reactive oxygen species (ROS) signals in osteoclastogenesis, while the accumulation of soluble Aβ₄₂ oligomers (Aβo) in periodontitis microenvironment further strengthened the signals and enhanced osteoclastogenesis through direct interactions with Trem2. Collectively, Trem2 mediated ROS signal amplification cascade was crucial in the process of osteoclastogenesis in periodontitis, suggesting the potential of Trem2 as a target for the prevention and treatment of bone destruction in periodontitis.

牙周炎是全球第六大流行疾病，与许多全身性疾病密切相关，影响整体健康。作为牙齿脱落的主要原因，牙周炎的特点是不可逆的牙槽骨丢失和活化的破骨细胞生成过程，这可能与破骨细胞中活化的细胞内活性氧（ROS）密切相关。在这里，我们证明了骨髓细胞 2 (Trem2) 上表达的触发受体是破骨细胞生成的关键调节因子，可调节牙周炎中的细胞内 ROS 信号。在本研究中，Trem2的表达通过 RNA-seq 评估，在诊断为慢性牙周炎的人牙槽骨中显着上调。在牙周炎小鼠模型中，在条件性敲除破骨细胞中的Trem2的情况下，牙槽骨吸收受到阻碍。此外，我们确定 Trem2/DAP12/Syk 依赖性级联是重要的细胞内信号传导，用于在破骨细胞生成过程中扩增活性氧 (ROS) 信号，而可溶性 Aβ _42的积累牙周炎微环境中的寡聚体 (Aβo) 通过与 Trem2 的直接相互作用进一步增强信号并增强破骨细胞生成。总的来说，Trem2 介导的 ROS 信号放大级联在牙周炎破骨细胞生成过程中至关重要，这表明 Trem2 作为预防和治疗牙周炎骨破坏的靶点的潜力。