Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Department of Prosthodontics, The First Clinical Division, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Front Immunol. 2024 Jul 16;15:1423378. doi: 10.3389/fimmu.2024.1423378. eCollection 2024.
Periodontitis, delineated by the destruction of structures that support teeth, is predominantly propelled by intricate immune responses. Immunomodulatory treatments offer considerable promise for the management of this ailment; however, the modulation of the periodontal immune microenvironment to facilitate tissue regeneration presents a substantial biomedical challenge. Herein, our study investigates the role of Wilms' tumor 1-associating protein (WTAP), a critical mA methyltransferase, in the immunomodulation of periodontitis and assesses its viability as a therapeutic target. We observed heightened expression of WTAP in macrophages extracted from gingival tissues impacted by periodontitis, with a strong association with M1 polarization. Via loss-of-function experiments, we demonstrated that diminishing WTAP expression precipitates a transition from M1 to M2 macrophage phenotypes amidst inflammatory conditions, thus improving the periodontal immune landscape. Further, RNA sequencing and indirect co-culture assays indicated that suppressing of WTAP expression modulates osteoimmune responses and enhances the osteogenic differentiation of bone marrow stromal cells. The local deployment of adeno-associated virus-shWTAP in murine models of periodontitis robustly validated the therapeutic promise of targeting WTAP in this disease. Collectively, our findings highlight the crucial role of WTAP in orchestrating macrophage-mediated osteoimmune responses and tissue regeneration in periodontitis, proposing novel avenues for immunotherapeutic interventions in its treatment.
牙周炎是由支持牙齿的结构破坏引起的，主要是由复杂的免疫反应推动的。免疫调节治疗为这种疾病的治疗提供了很大的希望；然而，调节牙周免疫微环境以促进组织再生是一个重大的生物医学挑战。在本研究中，我们研究了 Wilms 肿瘤 1 相关蛋白（WTAP）在牙周炎免疫调节中的作用，WTAP 是一种关键的 mA 甲基转移酶，并评估了其作为治疗靶点的可行性。我们观察到，在受牙周炎影响的牙龈组织中提取的巨噬细胞中，WTAP 的表达水平升高，与 M1 极化有很强的相关性。通过功能丧失实验，我们证明在炎症条件下，WTAP 表达的减少会促使巨噬细胞从 M1 向 M2 表型转变，从而改善牙周免疫状况。此外，RNA 测序和间接共培养实验表明，抑制 WTAP 表达可调节骨免疫反应，并增强骨髓基质细胞的成骨分化。在牙周炎的小鼠模型中局部应用腺相关病毒-shWTAP ，有力地验证了针对 WTAP 治疗这种疾病的治疗潜力。总的来说，我们的研究结果强调了 WTAP 在调节巨噬细胞介导的骨免疫反应和牙周炎组织再生中的关键作用，为该疾病的免疫治疗干预提供了新的途径。
