The study on orthodontic tooth movement and regulation of root resorption by Cathepsin L and Cathepsin L inhibitor.

组织蛋白酶L及组织蛋白酶L抑制剂对正畸牙移动及牙根吸收调节的研究。

• 批准号: 08672371
• 负责人: OHBA Tomoko
• 金额: $ 1.47万
• 依托单位: THE UNIVERSITY OF TOKUSHIMA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672371/
• 关键词: CATHEPSIN L; OSTEOCLAST; BONE RESORPTION; CATHEPSIN L INHIBITOR; EPOXYSUCCINYL PEPTIDE DERIVATIVES

In this study we evaluated a series of new synthetic epoxysuccinyl peptide derivatives. Inhibitory effects of these compounds on purified cathepsin L,B,H and J were tested using peptide substrates in vitro and five selected compounds (CLIK-1,63,65,88 and 90) were demonstrated that they were potent inhibitors for cathepsin L.Then, pit formation assay was employed to comfirm inhibitory effects of five compounds on rat osteoclast-mediated bone resorption. CLIK-1 inhibited cathepsin L activity at a concentration of 10^<-6> M,whereas no inhibition of cathepsin B was shown, and at this concentration CLIK-1 significantly suppressed pit formation stimulated by parathyroid hormone. 10^<-7> M of CLIK-63 inhibited cathepsin L activity completely and suppressed pit formation, and remaining activities of cathepsin J was shown but did not inhibit cathepsins B and H at concentrations of 10^<-7> and 10^<-6> M,respectively. CLIK-65 reduced pit formation at concentration of 10^<-7> M at which cathepsin L was inhibited completely and cathepsin J was suppressed moderately, but cathepsin B and H activities were not affected. CLIK-88 and 90 suppressed pit formation at concentrations of 10^<-5> and 10^<-4> M,respectively. At these concentrations, CLIK-88 and 90 completely blocked cathepsin L activity showing no inhibion for cathepsins B and H and weak suppression of cathepsin J.These data indicate that inhibition of cathepsin L in osteoclasts resulted in reduction of osteoclastic bone resorption and inhibitors of cathepsin L are effective at reducing osteoclast-mediated bone resorption. We are going to investigate bone remodeling mechanisms in alveolar bone during orthodintic tooth movement and regulation of root resorption using these new synthetic inhibitors of cathepsin L.

在这项研究中，我们评估了一系列新的合成环氧酸酯肽衍生物。这些化合物对纯化的组织蛋白酶L，B，H和J的抑制作用在体外使用肽底物进行了测试，并证明了五种选定的化合物（CLIK-1,63,65,88和90），证明它们对calterpsin l是有效的抑制剂。然后，使用坑形成测定五种化合物对大鼠破骨细胞介导的骨吸收的抑制作用。 CLIK-1在10^<-6> m的浓度下抑制了组织蛋白酶L活性，而没有抑制组织蛋白酶B的抑制作用，并且在这种浓度下，CLIK-1在甲状旁腺激素刺激的坑中显着抑制了凹坑形成。 10^<-7> m的Clik-63完全抑制了组织蛋白酶L活性并抑制了凹坑的形成，并且显示了组织蛋白酶J的剩余活性，但并未以10^<-7>的浓度抑制组织蛋白酶B和H -6> m，分别。 Clik-65在完全抑制组织蛋白酶L的10^<-7> m的浓度下降低了凹坑的形成，并且在中度抑制了组织蛋白酶J，但降低了组织蛋白酶J，但组织蛋白酶B和H活性受到影响。 Clik-88和90分别以10^<-5>和10^<-4> m的浓度抑制坑形成。在这些浓度下，Clik-88和90完全阻断了组织蛋白酶L活性，表现出对组织蛋白酶B和H的抑制作用，以及弱抑制组织蛋白酶。这些数据表明，这些数据抑制了骨质细胞中的骨蛋白酶L，从而导致骨质塑性骨吸收和抑制骨s骨的抑制作用。 L可有效减少破骨细胞介导的骨吸收。我们将使用这些新的组织蛋白酶L的新合成抑制剂来研究牙槽牙齿运动和根部吸收的牙槽骨骼的骨重塑机制。

项目成果

大庭 知子、大庭 康雄、他: "ラット軟骨におけるカテプシンLの免疫組織学的局在について" 第56回 日本矯正歯科学会大会 抄録集. 135 (1997)

Tomoko Ohba、Yasuo Ohba 等人：“大鼠软骨中组织蛋白酶 L 的免疫组织学定位”日本正畸学会第 56 届年会论文集 135（1997）。

Nobuhiko Katunuma, et al: "Molecular mechanisms of bone collagen degradation in bone resorption" Journal of Bone and Mineral Metabolism. 15. 1-8 (1997)

Nobuhiko Katunuma 等人：“骨吸收中骨胶原降解的分子机制”《骨与矿物质代谢杂志》。

Tomoko Ohba, Yasuo Ohba, Kenji Hiura, Teruko Takano-Yamamoto: "Immunocytochemical localization of cathepsin L in the rat cartilage" The 56th Annual Meeting of Japan Orthodontic Society. 135 (1997)

Tomoko Ohba、Yasuo Ohba、Kenji Hiura、Teruko Takano-Yamamoto：“组织蛋白酶 L 在大鼠软骨中的免疫细胞化学定位”日本正畸学会第 56 届年会。

Yasuo Ohba,Tomoko Ohba,et al: "Inhibitory mechanisms of H^+-ATPase inhibitor bafilomycin Al and carbonic anhydrase II inhibitor acetazolamide" FEBS Letters. 387. 175-178 (1996)

Yasuo Ohba，Tomoko Ohba，等人：“H 2 -ATP酶抑制剂巴弗洛霉素A1和碳酸酐酶II抑制剂乙酰唑胺的抑制机制”FEBS快报。

N.katsumuma, et al: "Molecular mechanisms of bone collagen degradation in bone resorption" Journal of Bone and Mineral Metabolism. 15. 1-8 (1997)

N.katsumuma 等人：“骨吸收中骨胶原降解的分子机制”《骨与矿物质代谢杂志》。