牙周炎是一种高度流行的慢性炎症性疾病，宿主免疫反应过度，导致牙周组织破坏和潜在的牙齿脱落。长非编码 RNA LncR-ANRIL 位于人类染色体 9p21 上，被认为是多种疾病的遗传风险因素，包括动脉粥样硬化、牙周炎、糖尿病和癌症。 LncR-APDC 是位于小鼠基因组 chr4 上的 ANRIL 的直系同源物。本研究旨在了解 lncR-APDC 在牙周炎进展中的调节作用。我们的实验结果是从诱发实验性牙周炎 (EP) 的 lncR-APDC 基因敲除 (KO) 小鼠中获得的，结果表明骨质流失加剧并破坏了促炎细胞因子的调节。从 lncR-APDC-KO 小鼠中采集的骨髓干细胞中发生成骨分化下调。此外，牙周炎牙龈组织的单细胞 RNA 测序显示，由于 lncR-APDC 沉默，免疫细胞（包括 T 细胞和 B 细胞、巨噬细胞和中性粒细胞）的比例和功能发生了变化。我们的研究结果还揭示了先前未识别的上皮细胞亚群，该亚群在 lncR-APDC-KO 组中独特存在。该上皮亚群的特征是 Krt8 和 Krt18 的阳性表达，通过各种配体-受体对与免疫细胞相互作用。 Tff2 的表达现在因其在慢性炎症条件下的作用而得到认可，在 lncR-APDC 缺陷小鼠的各种组织和细胞类型中表现出显着增加。此外，我们的研究揭示了 lncR-APDC 和 Tff2 之间直接结合相互作用的潜力。在 EP 模型中，牙龈内施用 AAV9-lncR-APDC 具有治疗效果。总之，我们的结果表明lncR-APDC在牙周病的进展中发挥着关键作用，并具有治疗牙周炎的潜力。此外，lncR-APDC沉默的EP模型中独特的上皮亚群的存在和显着升高的Tff2水平为牙周炎发病机制的表观遗传调控提供了新的视角。©作者。

Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of ANRIL located on mouse genome chr4. This study aims to comprehend the regulatory role of lncR-APDC in periodontitis progression. Our experimental findings, obtained from lncR-APDC gene knockout (KO) mice with induced experimental periodontitis (EP), revealed exacerbated bone loss and disrupted pro-inflammatory cytokine regulation. Downregulation of osteogenic differentiation occurred in bone marrow stem cells harvested from lncR-APDC-KO mice. Furthermore, single-cell RNA sequencing of periodontitis gingival tissue revealed alterations in the proportion and function of immune cells, including T and B cells, macrophages, and neutrophils, due to lncR-APDC silencing. Our findings also unveiled a previously unidentified epithelial cell subset that is distinctively presenting in the lncR-APDC-KO group. This epithelial subset, characterized by the positive expression of Krt8 and Krt18, engages in interactions with immune cells through a variety of ligand-receptor pairs. The expression of Tff2, now recognized for its role in chronic inflammatory conditions, exhibited a notable increase across various tissue and cell types in lncR-APDC deficient mice. Additionally, our investigation revealed the potential for a direct binding interaction between lncR-APDC and Tff2. Intra-gingival administration of AAV9-lncR-APDC was shown to have therapeutic effects in the EP model. In conclusion, our results suggest that lncR-APDC plays a critical role in the progression of periodontal disease and holds therapeutic potential for periodontitis. Furthermore, the presence of the distinctive epithelial subpopulation and significantly elevated Tff2 levels in the lncR-APDC-silenced EP model offer new perspectives on the epigenetic regulation of periodontitis pathogenesis.© The author(s).