Molecular biological analysis of tooth germ and odontogenic tumor

牙胚和牙源性肿瘤的分子生物学分析

• 批准号: 15209060
• 负责人: NAGAI Noriyuki
• 金额: $ 30.78万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209060/
• 关键词: Odontogenic tumor; Tooth germ; Ameloblastoma; Immunohistochemistry; In situ hybridization; Cell differentiaton; Protein expression; Gene expression; ヘパラナーゼ; ヘパラン硫酸; 口腔癌; ING; Notch; Jagged; Hes; Math; 遺伝子; 基底膜; IV型コラーゲン; α鎖; 成長因子; Ame

To clarify the characteristics of odontogenic tumors and the mechanism of tooth germ development, we investigated several gene and protein expressions through molecular biological analysis.1.The expression pattern of Amelogenin gene in ameloblastoma was different from that of the tooth germ. It was suggested that epigenetic change in sex chromosomes might have some correlations in the tumorigenesis of ameloblastoma.2.The immunolocalization of type IV collagen alpha chains in benign odontogenic tumor was similar to that of the tooth germ but a different pattern was observed in malignant odontogenic tumor. The alpha chain-staining pattern in malignant odontogenic tumors was irregular.3.We examined the expressions of Notch1, HES5, Jagged2 and Math1 in molar tooth germ by using in situ hybridization. Our results suggest that Notch1 signaling pathway through Jagged2 has an important effect on Math1, regulating odontogenesis through lateral specification and inductive signaling.4.We investigated the localization of heparanase and heparan sulphate proteoglycan (HSPG) in tooth germ and odontogenic tumors. We suggest that : 1) the increase in immunolocalization of heparanase molecules may be a responsible factor for the neoplastic growth of odontogenic tissues. 2) the main function of heparanase in normal odontogenic tissue may be local modulation of HSPG and heparan sulphate-bound bioactive molecules. 3) the function of heparanase is locally and tightly regulated in normal tooth germ and to some extent in benign odontogenic tumors. 4) the change in localization of HSPG and increased immunoexpression of heparanase in neoplastic cells may represent the malignant progression of ameloblastoma to ameloblastic carcinoma.

为了阐明牙源性肿瘤的特点和牙胚发育的机制，本研究通过分子生物学分析，对几种基因和蛋白的表达进行了研究。1.釉原蛋白基因在成釉细胞瘤中的表达模式与牙胚不同。提示性染色体的表观遗传学改变可能与成釉细胞瘤的发生有关。2. Ⅳ型胶原α链在良性牙源性肿瘤中的免疫定位与牙胚相似，而在恶性牙源性肿瘤中的免疫定位与牙胚不同。牙源性恶性肿瘤中α链的染色模式不规则。3.应用原位杂交技术检测Notch1、HES5、Jagged2和Math1在磨牙牙胚中的表达。我们的研究结果表明Notch1信号通路通过Jagged2对Math1有重要影响，通过侧向特异性和诱导性信号调节牙发生。4.研究了乙酰肝素酶和硫酸乙酰肝素蛋白多糖（HSPG）在牙胚和牙源性肿瘤中的定位。我们建议：1）肝素酶分子免疫定位的增加可能是牙源性组织肿瘤生长的原因之一。2)乙酰肝素酶在正常牙源性组织中的主要功能可能是局部调节HSPG和硫酸乙酰肝素结合的生物活性分子。3)乙酰肝素酶的功能在正常牙胚中局部和紧密地调节，并且在一定程度上在良性牙源性肿瘤中调节。4)成釉细胞瘤中HSPG的定位改变和乙酰肝素酶的免疫表达增加可能代表成釉细胞瘤向成釉细胞癌的恶性进展。

项目成果

Microcystic adnexal carcinoma with mandibular bone marrow involvement : a case report with immunohistochemistry.

下颌骨骨髓受累的微囊性附件癌：免疫组织化学病例报告。

• 发表时间: 2006
• 期刊: Am J Dermatopathol. 28(6)
• 作者: T.Moriyama;T.Iida;K.Kobayashi;T.Higashi;T.Fukuoka;H.Tsumura;C.Leon;N.Suzuki;K.Inoue;C.Gachet;K.Noguchi;M.Tominaga;Nagatsuka H
• 通讯作者: Nagatsuka H

Efficacy of atelocollagen honeycomb scaffold in bone formation using KUSA/Al cells

使用 KUSA/Al 细胞进行去端肽胶原蜂窝支架在骨形成中的功效

• 发表时间: 2006
• 期刊: J Biomed Mater Res A 77(4)
• 作者: Fujimoto M.;Isobe M.;Yamaguchi S.;Amagasa T;et al.;Rodriguez AP
• 通讯作者: Rodriguez AP

Expression of Notch1 and Math1 in mandibular condyle cartilage in neonatal mice.

Notch1和Math1在新生小鼠下颌髁突软骨中的表达。

• 发表时间: 2005
• 期刊: Angle Orthod. 75(6)
• 作者: Kashiwagi;H.;Shimizu T
• 通讯作者: Shimizu T

Immunohistochemical examination of cytological differentiation in osteosarcomas.

骨肉瘤细胞学分化的免疫组织化学检查。

• 发表时间: 2005
• 期刊: Eur J Med Res. 10(11)
• 作者: 古川 桂;亀井宏行;阿児雄之;Kawakami T
• 通讯作者: Kawakami T

Expression of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in rat osteoporosis induced by immunosuppressant FK506

• DOI: 10.1016/j.bone.2003.05.003
• 发表时间: 2004-03-01
• 期刊: BONE
• 影响因子: 4.1
• 作者: Fukunaga, J;Yamaai, T;Sugahara, T
• 通讯作者: Sugahara, T