Role of osteopoutin in homeostasis of bone tissue

骨连接蛋白在骨组织稳态中的作用

• 批准号: 10470058
• 负责人: NOMURA Shintaro
• 金额: $ 7.49万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470058/
• 关键词: osteopontin; homeostasis; bone resorption; bone tissue; osteocyte; transcription; integrin; osleoclact; メカニカルストレス; 遺伝子発現; 骨芽細胞; 転写因子; プロモーター

Molecular mechanism of bone remodeling caused by mechanical stress is unknown. In this project, we identified osteopontin (Opn) as the trigger of bone remodeling. Experimental bone remodeling system developed by Waldo et al was used for the study. A 0.5mm diameter of elastic band was inserted interproximally among the upper first and second molar on both side. After 12 hours of treatment, Opn expression was detected in the osteocytes on the pressure side, and gradually spread to those on the tension side. Only 3% of the osteocytes located on the pressure side expressed Opn in the control rats. In contrast, the value was increased to 88% at 48 hoturs. Following the increased expression of Opn, a 17-fold greater number of osteoclasts compared with the control and numerous resorption pits were observed on the pressure side of the alveolar bone. Injection of RGDS-peptide strongly inhibited the increase in the number of osteoclasts. The results indicate that Opn is an important factor triggering bone remodeling caused by mechanical stress. Furthermore, Opn was identified as the crucial factor of the homeostasis of bone.

机械应力引起骨重塑的分子机制尚不清楚。在这个项目中，我们发现骨桥蛋白（Opn）是骨重塑的触发因子。本研究采用Waldo等人开发的实验性骨重塑系统。在双侧第一磨牙和第二磨牙近端间插入直径0.5mm的弹力带。治疗12小时后，在压力侧骨细胞中检测到Opn表达，并逐渐向张力侧骨细胞扩散。在对照大鼠中，位于压力侧的骨细胞中只有3%表达Opn。相比之下，在48小时时，该值增加到88%。Opn表达增加后，破骨细胞数量比对照增加了17倍，在牙槽骨受压侧观察到大量的吸收凹坑。注射rgds肽可明显抑制破骨细胞数量的增加。结果表明，Opn是引发机械应力引起骨重塑的重要因素。此外，Opn被认为是骨稳态的关键因素。

项目成果

T.Maekawa, Nomura S. et al: "Mouse ATF2 null mutants display features of severe type of meconium aspiration syndrome"J.Biol.Chem.. 274. 17813-17819 (1999)

T.Maekawa、Nomura S. 等人：“小鼠 ATF2 无效突变体表现出严重胎粪吸入综合征的特征”J.Biol.Chem.. 274. 17813-17819 (1999)

M.Sato, T.Ochi, T.Nakase, S.Hirota, Y.Kitamura, S.Nomura and N.Yasui: "Mechanical tension-stress induces expression of BMP-2 and -4, butnot BMP-6, -7 and GDF-5 mRNA, during distraction osteogenesis."J.Bone and Mineral Research.. 14. 1084-1095 (1999)

M.Sato、T.Ochi、T.Nakase、S.Hirota、Y.Kitamura、S.Nomura 和 N.Yasui：“机械张力应激诱导 BMP-2 和 -4 的表达，但不诱导 BMP-6、-7 的表达

Terai K,, Nomura S. et al.: "The role of osteopontin in the bone remodeling caused by mechanical stress"J.Bone and Mineral Res.. 14. 839-849 (1999)

Terai K,, Nomura S.等：“骨桥蛋白在机械应力引起的骨重塑中的作用”J.Bone and Mineral Res.. 14. 839-849 (1999)

K.Terai, T.Takano-Yamamoto, Y.Ohba, K.Hiura, M.Sugimoto, M.Sato, H.Kawahata, N.Inagura, Y.Kitamura and S.Nomura.: "The role of osteopontin in the bone remodeling caused by mechanical stress."J.Bone and Mineral Research.. 14. 839-849 (1999)

K.Terai、T.Takano-Yamamoto、Y.Ohba、K.Hiura、M.Sugimoto、M.Sato、H.Kawahata、N.Inagura、Y.Kitamura 和 S.Nomura。：“骨桥蛋白在

H.Ogihara, T.Kannno, E.Morii, D-K.Kim, Y-M.Lee, M.Sato, W-Y.Kim, S.Nomura, Y.Ito and Y.Kitamura: "Synergy of PEBP2/CBF with mi transcription factor (MITF) for transactivation of mouse mast cell protease 6 gene."Oncogene. 18. 4632-4639 (1999)

H.Ogihara、T.Kannno、E.Morii、D-K.Kim、Y-M.Lee、M.Sato、W-Y.Kim、S.Nomura、Y.Ito 和 Y.Kitamura：“PEBP2/CBF 与 mi 转录因子的协同作用