Elucidation of roles and functions of cementoblasts in the destruction and regeneration of periodontal tissue

阐明成牙骨质细胞在牙周组织破坏和再生中的作用和功能

• 批准号: 15592185
• 负责人: NOGUCHI Kazuyuki
• 金额: $ 2.24万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592185/
• 关键词: mouse; cementoblast; periodontopathic bacteria; LPS; IL-6; COX-2; PGE2; IL-1; IL-1α

In the present study, we investigated whether a mouse cementoblast cell line, OC-CM 30 cells, stimulated with interleukin(IL)-1α or lipopolysaccharides (LPS) from Prophyomonas(P.) gingivalis and Actinobacillus(A.) actinomycetemcomitans produced COX-2-dependent PGE_2 and furthermore whether the produced PGE_2 affected IL-1α-induced IL-6 production. IL-1α and LPS from P.gingivalis and A.actinomycetemcomitans time-dependently induced PGE_2 production. Indomethacin (a COX-1/-2 inhibitor) and NS-398 (a COX-2 inhibitor) completely inhibited IL-1 α-and LPS-induced PGE_2 production. 17-phenyl-ω-trinor PGE_2 (an EP_1 agonist) and ONO-AE1-329 (an EP_4 agonist) mimicked PGE_2 enhancement of IL-1α-and LPS from P.gingivalis and A.actinomycetemcomitans induced IL-6 production in OC-CM 30 cells. Furthermore, we investgated the effect of PGE_2 on RANKL and OPG expression. PGE_2 did not enhance RANKL and OPG prtotein expression. From these data, we suggest that in OC-CM 30 cells IL-1α and LPS from P.gingivalis and A.actinomycetemcomitans induced PG_2 production in a COX-2-dependent manner and that the COX-2-derived PGE_2 up-regulates IL-1α-and LPS from P.gingivalis and A.actinomycetemcomitans elicited IL-6 production via EP_1 and/or EP_4 receptors. PGE_2 and IL-6 produced by cementoblasts may be involved in the pathogenesis of periodontal disease.

本研究以小鼠成牙骨质细胞系OC-CM 30细胞为研究对象，观察了白细胞介素（IL）-1α或脂多糖（LPS）对成牙骨质细胞系OC-CM 30细胞增殖的影响。gingivalis和放线杆菌（A.）放线菌共生菌产生考克斯-2依赖的PGE_2，并进一步研究所产生的PGE_2是否影响IL-1α诱导的IL-6的产生。牙龈卟啉单胞菌和伴放线菌的IL-1α和LPS诱导PGE_2的产生具有时间依赖性。考克斯1/-2抑制剂消炎痛和考克斯2抑制剂NS-398可完全抑制IL-1 α和LPS诱导的PGE_2生成。17-phenyl-ω-trinor PGE_2（EP_1激动剂）和ONO-AE 1 -329（EP_4激动剂）模拟PGE_2增强IL-1α和牙龈卟啉单胞菌和伴放线放线菌LPS诱导OC-CM 30细胞产生IL-6。进一步研究PGE_2对RANKL和OPG表达的影响。PGE_2对RANKL和OPG蛋白表达无明显影响。提示牙龈卟啉单胞菌和伴放线菌的IL-1α和LPS以考克斯-2依赖的方式诱导OC-CM 30细胞产生PG_2，而考克斯-2诱导的PGE_2通过EP_1和/或EP_4受体上调IL-1α和LPS诱导IL-6的产生。成牙骨质细胞分泌PGE_2和IL-6可能参与牙周病的发病。

项目成果

Effects of nonsurgical periodontal therapy on the microbiota.

• DOI: 10.1111/j.1600-0757.2004.03675.x
• 发表时间: 2004-10
• 期刊: Periodontology 2000
• 影响因子: 18.6
• 作者: M. Umeda;Y. Takeuchi;K. Noguchi;Yi Huang;Geena Koshy;I. Ishikawa

Cycooxygenase-2 dependent PGE_2 down-regulates MMP-3 production via EP2/EP4 subtypes of PGE_2 receptors in human PDL cells stimulated with IL-1α

在IL-1α刺激的人PDL细胞中，Cycooxygenase-2依赖性PGE_2通过PGE_2受体的EP2/EP4亚型下调MMP-3的产生

• 期刊: Journal of Periodontology (In Press)
• 作者: 根来 武史;Takefumi Negoro etc.;Miyauchi M et al.;Yan M et al.
• 通讯作者: Yan M et al.

Down-regulation of interkeukin-1a-induced matrix-metalloproteinase-13 expression via EP1 receptors by PGE_2 in human periodontal ligament cells

PGE_2 通过 EP1 受体下调人牙周膜细胞中白细胞介素 1a 诱导的基质金属蛋白酶 13 表达

• 发表时间: 2005
• 期刊: Oral Microbiol Immunol 20
• 作者: K Noguchi;SMPS Ruwanpura;M Yan;N Yoshida;I Ishikawa.
• 通讯作者: I Ishikawa.

Down-regulation of interleukin-1a-induced matrix metallopproteionase-13 expression via EP1 receptors by PGE2 in human periodontal ligament cells

PGE2 通过 EP1 受体下调人牙周膜细胞中白细胞介素 1a 诱导的基质金属蛋白酶 13 表达

• 发表时间: 2005
• 期刊: Oral Microbiology and Immunology 20(1)
• 作者: 小川清隆;丹羽健;宮澤健;青木泰樹;後藤滋巳;Noguchi K et al.
• 通讯作者: Noguchi K et al.

Down-regulation of interleukin-1α-induced matrix metallopproteionase-13 expression via EP1 receptors by PGE_2 in human periodontal ligament cells

PGE_2 通过 EP1 受体下调人牙周膜细胞中白细胞介素 1α 诱导的基质金属蛋白酶 13 表达

• 发表时间: 2005
• 期刊: Oral Microbiology and Immunology 20(1)
• 作者: Taiju Aoki;Kiyotaka Ogawa;Ken Miyazawa;Tatsushi Kawai;Shigemi Goto;荻原さつき;Noguchi K et al.
• 通讯作者: Noguchi K et al.