Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, 639 Zhizaoju Road, Shanghai, China.
Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai, China.
J Dent Res. 2023 Jan;102(1):72-81. doi: 10.1177/00220345221116927. Epub 2022 Aug 18.
Nuclear receptor corepressor 1 () has been reported to regulate different transcription factors in different biological processes, including metabolism, inflammation, and circadian rhythms. However, the role of in periodontitis has not been elucidated. The aims of the present study were to investigate the role of in experimental periodontitis and to explore the underlying mechanisms through an experimental periodontitis model in myeloid cell-specific -deficient mice. Myeloid cell-specific knockout (MNKO) mice were generated, and experimental periodontitis induced by ligation using 5-0 silk sutures was established. 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 on myeloid cells. RNA sequencing was used to explore the differentially targeted genes in osteoclastogenesis in the absence of . Coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) experiments, and dual luciferase assays were performed to explore the relationship between 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 () 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 . In conclusion, deficiency promoted osteoclast and neutrophil formation in mice with experimental periodontitis. It regulated the transcription of via PPARγ to promote osteoclast differentiation.
核受体辅助抑制因子 1 (Nuclear receptor corepressor 1, ) 已被报道在不同的生物学过程中调节不同的转录因子，包括代谢、炎症和昼夜节律。然而，在牙周炎中 的作用尚未阐明。本研究旨在探讨 在实验性牙周炎中的作用，并通过髓样细胞特异性 - 缺陷小鼠的实验性牙周炎模型来探索潜在的机制。生成了髓样细胞特异性 敲除 (Myeloid cell-specific knockout, MNKO) 小鼠，并通过用 5-0 丝线结扎建立实验性牙周炎。用 基因敲入 (flox/flox) 小鼠作为同窝对照 (Littermate controls, LC)。通过组织学染色和微计算机断层扫描评估破骨细胞生成和牙槽骨吸收。通过流式细胞术观察 对髓样细胞的影响。通过 RNA 测序探索在破骨细胞生成中缺乏 时的差异靶向基因。通过共免疫沉淀 (Co-immunoprecipitation, Co-IP)、染色质免疫沉淀 (Chromatin immunoprecipitation, ChIP) 实验和双荧光素酶测定来探索 与靶向基因之间的关系。牙周炎诱导后和体外破骨细胞生成中，MNKO 小鼠的牙槽骨吸收明显大于 LC 小鼠。MNKO 小鼠牙龈组织中 CD11b+细胞，特别是 CD11b+Ly6G+中性粒细胞的比例明显高于 LC 小鼠。RNA 测序结果表明，CCAAT 增强子结合蛋白α (CCAAT enhancer binding protein α, ) 是 MNKO 和 LC 组之间差异表达最明显的基因之一。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 (Peroxisome proliferator-activated receptor gamma, PPARγ) 相互作用，并与组蛋白去乙酰化酶 3 (Histone deacetylase 3, HDAC3) 合作控制 的转录。总之，在实验性牙周炎小鼠中， 缺乏促进破骨细胞和中性粒细胞的形成。它通过 PPARγ 调节 的转录，以促进破骨细胞分化。
