Identification creation of bioactive sites of enamel proteins for developing a new therapy of periodontal tissue regeneration.

鉴定牙釉质蛋白生物活性位点的创建，以开发牙周组织再生的新疗法。

• 批准号: 14370583
• 负责人: TAKATA Takashi
• 金额: $ 8.83万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370583/
• 关键词: enamel proteins; ameloblastin; periodontal tissue; tissue regeneration; peptide; periodontal ligament; calcification; cementum; 歯周靭帯細胞; 骨芽細胞; シグナル伝達

To identify the bioactive components and sites in Emdogain (EMD), which is widely used as a periodontal regenerative therapy, and to explore the possibility of developing new medicament using the synthetic peptide of the active sites for periodontal tissue regeneration, we achieved the following studies. 1.Cellular and molecular mechanism of stimulative effects of EMD on proliferation and differentiation of periodontal cells such as periodontal ligament cells (PDLC), gingival epithelial cells, gingival fibroblasts and osteoblasts. 2.Signal pathways and receptors of EMD, 3.Determination of active components and sites of EMD, and 4.Effects of the synthetic peptide of the active site on PDLC proliferation and differentiation in vitro and periodontal tissue regeneration in vivo. The results of the studies were 1.EMD stimulated proliferation and differentiation of PDLC and osteoblasts and inhibited those of gingival epithelial cells and fibroblasts, 2.RTK-ERK 1/2 pathway was possibly involved in mitogenic response of PDLC to EMD, 3.An anti-ameloblastin antibody suppressed stimulatory effects of EMD on PDLC proliferation and differentiation, and 4.The synthetic peptide of the active site of ameloblastin stimulated proliferation and differentiation of PDLC and periodontal tissue regeneration. In conclusions, EMD has suitable bioactivities to periodontal tissue regeneration and the synthetic peptide determined in the present study could be used as a new periodontal tissue regeneration therapy.

为了鉴定广泛用于牙周再生治疗的Emdogain（EMD）的生物活性成分和位点，并探索利用活性位点的合成肽开发用于牙周组织再生的新药物的可能性，我们进行了以下研究。 1.EMD促进牙周膜细胞（PDLC）、牙龈上皮细胞、牙龈成纤维细胞和成骨细胞等牙周细胞增殖和分化的细胞和分子机制。 2.EMD信号通路及受体，3.EMD活性成分及位点的测定，4.活性位点合成肽对PDLC体外增殖分化及体内牙周组织再生的影响。研究结果为：1.EMD刺激PDLC和成骨细胞的增殖和分化，抑制牙龈上皮细胞和成纤维细胞的增殖和分化；2.RTK-ERK 1/2通路可能参与PDLC对EMD的有丝分裂反应；3.An抗成釉素抗体抑制EMD对PDLC增殖和分化的刺激作用，4.成釉素活性位点的合成肽刺激增殖和分化PDLC 和牙周组织再生。综上所述，EMD对牙周组织再生具有合适的生物活性，本研究确定的合成肽可作为一种新的牙周组织再生疗法。

项目成果

Establishment of cementoblast cell lines from rat cementum lining cells by transfection with temperature-sensitive simian virus-40 T-antigen gene.

通过转染温度敏感的猿猴病毒 40 T 抗原基因，从大鼠牙骨质衬里细胞中建立成牙骨质细胞系。

• 发表时间: 2005
• 期刊: Bone 37
• 作者: Kitagawa;M.;et al.
• 通讯作者: et al.

北川尚嗣他: "歯周組織細胞の増殖分化に対するアメロブラスチン断片合成ペプチドの影響"広島大学歯学雑誌. 35. 226 (2003)

Naoji Kitakawa 等：“成釉素片段合成肽对牙周组织细胞增殖和分化的影响”广岛大学牙科杂志 35. 226 (2003)。

歯周組織とエナメルタンパク

牙周组织和牙釉质蛋白

• 发表时间: 2002
• 作者: 高田 隆

Matsuda N.: "Possible involvement of extracellular signal-related ilnase 1/2 in mitogenic response of periodontal ligament cells to enamel matrix delivative"European Journal of Oral Sciences. 110. 439-444 (2002)

Matsuda N.：“细胞外信号相关的伊恩酶 1/2 可能参与牙周膜细胞对牙釉质基质衍生物的有丝分裂反应”欧洲口腔科学杂志。

Enhanced DNA synthesis accompanied by constitutive phosphorylation of the ERK pathway in human fibroblasts cultured on a polyelectrolyte complex.

• DOI: 10.1016/s0142-9612(03)00375-2
• 发表时间: 2003-11
• 期刊: Biomaterials
• 影响因子: 14
• 作者: N. Matsuda;M. Horikawa;Masahiro Yoshida;M. Watanabe;M. Nagahata;A. Teramoto;K. Abe