Expression and function of RANKL in gingival epithelialum

牙龈上皮中RANKL的表达及功能

• 批准号: 23792487
• 负责人: USUI Michihiko
• 金额: $ 2.66万
• 依托单位: Kyushu Dental College (2012)Showa University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23792487/
• 关键词: 歯肉上皮細胞; RANKL; PKA signaling; 破骨細胞形成; 歯肉上皮; ＲＡＮＫＬ

Periodontitis is a chronic inflammatory disease characterized by the destruction of alveolar bone. Receptor activator of nuclear factor kappa B ligand (RANKL) is known to be an essential factor for osteoclastogenesis. Recent clinical studies indicate that levels of RANKL in the gingival crevicular fluid are increased in periodontitis patients. Although the gingival sulcus is liend by gingival epithelial cells (GECs), RANKL expression in GECs is not fully understood. RT-PCR, western blotting and immunohistochemistry were performed to confirm RANKL expression in GECs and in gingival tissue. Ca9-22 cells, a human gingival epithelial cell line, were treated with tumor necrosis factor (TNF)-α, antibodies against TNF receptors, and an inhibitor and an activator of PKA signaling. The levels of RANKL expression were examined by real time PCR and western blotting. GECs and bone marrow-derived osteoclast precursors were co-cultured to examine the effect of GECs-produced RANKLon osteoclast formation. RANKL mRNA and protein were expressed in GECs. Immunohistochemistry also showed RANKL and TNF-α expression in gingival epithelium, but not in gingival connective tissue. TNF-α increased the levels of RANKL expression in GECs. TNF-α-induced RANKL expression was inhibited by antibody against TNF receptor type 1 (TNFR1) and an inhibitor of PKA signaling. GECs constitutively induced osteoclast formation. This effect was increased significantly by TNF-α and activator of PKA signaling, and prevented by RANK-Fc.TNF-α induces RANKL expression through PKA signaling in GECs, which regulate osteoclastogenesis. GECs may take part in progression of alveolar bone destruction by periodontitis.

牙周炎是一种慢性炎症性疾病，其特征是肺泡骨的破坏。核因子Kappa B配体（RANKL）的受体激活因素是破骨细胞生成的重要因素。最近的临床研究表明，牙周炎患者中牙龈裂纹液的RANKL水平有所增加。尽管牙龈沟是由牙龈上皮细胞（GEC）释放的，但GEC中的RANKL表达不是RT-PCR，但进行了蛋白质印迹和免疫组织化学，以确认在GEC中和牙龈组织中的RANKL表达。 CA9-22细胞是一种人类牙龈上皮细胞系，用肿瘤坏死因子（TNF）-α，针对TNF受体的抗体以及PKA信号传导的抑制剂和激活剂处理。通过实时PCR和Western印迹检查了RANKL表达的水平。将GEC和骨髓来源的破骨细胞前体共培养，以检查GEC生产的Ranklon骨骨细胞形成的作用。 RANKL mRNA和蛋白质在GEC中表达。免疫组织化学在牙龈上皮中还显示出RANKL和TNF-α的表达，但在牙龈结缔组织中却没有。 TNF-α增加了GEC中RANKL表达的水平。 TNF-α诱导的RANKL表达被抗体对TNF受体1型（TNFR1）和PKA信号传导的抑制剂抑制。 GEC组成诱导的破骨细胞形成。 TNF-α和PKA信号的激活因素显着提高了这种效果，并通过rank-fc.tnf-α预防，可通过GEC中的PKA信号传导诱导RANKL表达，从而调节骨质质构成。 GEC可能参与牙周炎肺泡骨破坏的进展。

项目成果

TNF-α induces RANKL expression・・・・

TNF-α诱导RANKL表达・・・

• 发表时间: 2011
• 作者: Usui M;Fujihara R;Yano A;Saito A;Yamamoto M.
• 通讯作者: Yamamoto M.

actinomycetemcomitans LPS Enhances Foam Cell Formation Induced

放线菌 LPS 增强诱导的泡沫细胞形成

• 发表时间: 2012
• 期刊: LDL.Journal of Dental Research
• 作者: Morishita A;Ariyoshi W;Okinaga T;Usui M;Nakashima K;Nishihara T A
• 通讯作者: Nishihara T A

Effect of titanium surface decontamination using A Newly developed ultrasonic water jet cleaner

新研制的超声波水射流清洗机对钛表面去污效果

• 发表时间: 2012
• 作者: Takiguchi T;(5名)
• 通讯作者: (5名)

The New Frontiers in Research for Oral Cancer

口腔癌研究的新前沿

• 发表时间: 2012
• 作者: Takami M;Miyamoto A;Matsumoto A;Mochizuki A;Tachi K;Baba K;Inoue T;Mijung Y;Shibuya I;Zhao B;Kamijo R
• 通讯作者: Kamijo R

超音波照射のヒト歯肉上皮細胞に対する影響について

超声照射对人牙龈上皮细胞的影响

• 发表时间: 2011
• 期刊: 日本歯科保存学会誌
• 作者: 臼井通彦;滝口尚;史春;Enkhzaya Guruudivaa;宮澤康;菅野真莉加;野瀬冬樹;斎藤彰大;菊池真理子;冨永和宏;西原達次;根岸洋一,山本松男
• 通讯作者: 根岸洋一,山本松男