Nuclear receptor corepressor 1 (Ncor1) has been reported to regulate different transcription factors in different biological processes, including metabolism, inflammation, and circadian rhythms. However, the role of Ncor1 in periodontitis has not been elucidated. The aims of the present study were to investigate the role of Ncor1 in experimental periodontitis and to explore the underlying mechanisms through an experimental periodontitis model in myeloid cell–specific Ncor1-deficient mice. Myeloid cell–specific Ncor1 knockout (MNKO) mice were generated, and experimental periodontitis induced by ligation using 5-0 silk sutures was established. Ncor1 flox/flox mice were used as littermate controls (LC). Histological staining and micro–computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. Flow cytometry was conducted to observe the effect of Ncor1 on myeloid cells. RNA sequencing was used to explore the differentially targeted genes in osteoclastogenesis in the absence of Ncor1. Coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) experiments, and dual luciferase assays were performed to explore the relationship between NCoR1 and the targeted gene. Alveolar bone resorption in the MNKO mice was significantly greater than that in the LC mice after periodontitis induction and osteoclastogenesis in vitro. The percentage of CD11b+ cells, particularly CD11b+ Ly6G+ neutrophils, was substantially higher in gingival tissues in the MNKO mice than in the LC mice. Results of RNA sequencing demonstrated that CCAAT enhancer binding protein α (Cebpα) was one of the most differentially expressed genes between the MNKO and LC groups. Mechanistically, Co-IP assays, ChIP experiments, and dual luciferase assays revealed that NCOR1 interacted with peroxisome proliferator-activated receptor gamma (PPARγ) and cooperated with HDAC3 to control the transcription of Cebpα. In conclusion, Ncor1 deficiency promoted osteoclast and neutrophil formation in mice with experimental periodontitis. It regulated the transcription of Cebpα via PPARγ to promote osteoclast differentiation.

据报道，核受体辅抑制因子 1 ( Ncor1 ) 在不同的生物过程中调节不同的转录因子，包括新陈代谢、炎症和昼夜节律。然而， Ncor1在牙周炎中的作用尚未阐明。本研究的目的是研究Ncor1在实验性牙周炎中的作用，并通过骨髓细胞特异性Ncor1缺陷小鼠的实验性牙周炎模型探索其潜在机制。生成了骨髓细胞特异性Ncor1敲除 (MNKO) 小鼠，并建立了使用 5-0 丝线结扎诱导的实验性牙周炎。Ncor1flox/flox 小鼠用作同窝对照 (LC)。组织学染色和显微计算机断层扫描用于评估破骨细胞生成和牙槽骨吸收。流式细胞术观察Ncor1对髓系细胞的影响。在没有Ncor1的情况下，RNA 测序用于探索破骨细胞生成中的差异靶向基因。进行免疫共沉淀 (Co-IP)、染色质免疫沉淀 (ChIP) 实验和双荧光素酶测定以探索NCoR1与 NCoR1 之间的关系和目标基因。在体外诱导牙周炎和破骨细胞生成后，MNKO 小鼠的牙槽骨吸收明显高于 LC 小鼠。MNKO 小鼠牙龈组织中 CD11b+ 细胞（尤其是 CD11b+ Ly6G+ 中性粒细胞）的百分比明显高于 LC 小鼠。RNA 测序结果表明，CCAAT 增强子结合蛋白 α ( Cebpα ) 是 MNKO 和 LC 组之间表达差异最大的基因之一。从机制上讲，Co-IP 测定、ChIP 实验和双荧光素酶测定表明 NCOR1 与过氧化物酶体增殖物激活受体 γ (PPARγ) 相互作用，并与 HDAC3 协同控制 Cebpα 的转录。总之，Ncor1缺乏促进实验性牙周炎小鼠的破骨细胞和中性粒细胞形成。它通过 PPARγ 调节Cebpα的转录以促进破骨细胞分化。