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LncRNA Nron 抑制牙周炎中的骨吸收。

LncRNA Nron Inhibits Bone Resorption in Periodontitis.

机构信息

Department of Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.

Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, China.

出版信息

J Dent Res. 2022 Feb;101(2):187-195. doi: 10.1177/00220345211019689. Epub 2021 Jun 22.

Abstract

Periodontitis is the most common chronic oral disease and is characterized by active osteoclast activity and significant alveolar bone resorption. However, the key regulatory factors of periodontal bone loss have yet to be determined, and reasonable intervention methods for periodontitis have not been developed. Currently, long noncoding RNAs (lncRNAs) have shown a remarkable ability to maintain normal cell and tissue homeostasis. Interestingly, we recently found that the lncRNA Nron is negatively correlated with alveolar bone resorption in periodontitis model. To explore the role of Nron in periodontal bone loss, osteoclastic-specific Nron knockout mice and osteoclastic-specific Nron transgenic mice were generated. Nron effectively inhibited osteoclastogenesis and alveolar bone resorption. Mechanistically, Nron was found to effectively promote the nuclear transport of NF-κb repressing factor (NKRF). In addition, NKRF in the nucleus significantly repressed the transcription of Nfatc1, which is a major NF-κb signaling molecule. Importantly, local injection of the Nron overexpression vector significantly inhibited osteoclastogenesis and alveolar bone resorption, which indicated the translational application potential of lncRNAs in the treatment of bone resorption in periodontitis.

摘要

牙周炎是最常见的慢性口腔疾病,其特征为破骨细胞活性活跃和明显的牙槽骨吸收。然而,牙周炎骨丢失的关键调节因子尚未确定,也尚未开发出针对牙周炎的合理干预方法。目前,长链非编码 RNA(lncRNA)在维持正常细胞和组织稳态方面表现出显著的能力。有趣的是,我们最近发现 lncRNA Nron 与牙周炎模型中的牙槽骨吸收呈负相关。为了探讨 Nron 在牙周炎骨丢失中的作用,我们生成了破骨细胞特异性 Nron 敲除小鼠和破骨细胞特异性 Nron 转基因小鼠。Nron 有效抑制破骨细胞生成和牙槽骨吸收。从机制上讲,发现 Nron 可有效促进核因子 κB 抑制因子(NKRF)的核转运。此外,核内的 NKRF 显著抑制 NF-κB 信号通路中的主要分子 NFATC1 的转录。重要的是,Nron 过表达载体的局部注射显著抑制了破骨细胞生成和牙槽骨吸收,这表明 lncRNA 在牙周炎骨吸收治疗中的转化应用潜力。

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