Elucidation of bone formation signal aimed at the development of medical treatment of osteoporosis induced by deterioration of bone formation

阐明骨形成信号，旨在开发骨形成恶化引起的骨质疏松症的药物治疗

• 批准号: 22590656
• 负责人: SUGIMOTO Toshitsugu
• 金额: $ 2.83万
• 依托单位: Shimane University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590656/
• 关键词: 老年医学; 骨粗鬆症; 骨形成; 骨芽細胞; 副甲状腺ホルモン; 骨形成因子; Tmem119; 小胞体ストレス; 筋芽細胞; 終末糖化産物; Smad3; Wnt; βカテニン; カルシウム感知受容体; ストロンチウム; MAPキナーゼ

We demonstrated that strontium exhibited anabolic action on bone partly through activating calcium-sensing receptor. We identified a smad3-related factor, Tmem119, which is induced by parathyroid hormone(PTH) and promotes osteoblast differentiation partly via Wnt signal and cross-talk with bone morphogenetic protein-Runx2 pathway. Endoplasmic reticulum stress pathway is involved in the differentiation of myoblasts into osteoblasts enhanced by Tmem119. Advanced glycation end-products inhibits osteoblast differentiation via the suppression of this pathway.

我们证明锶部分通过激活钙敏感受体对骨表现出合成代谢作用。我们鉴定了一个 smad3 相关因子 Tmem119，它由甲状旁腺激素 (PTH) 诱导，部分通过 Wnt 信号和与骨形态发生蛋白 Runx2 通路的串扰促进成骨细胞分化。内质网应激途径参与 Tmem119 增强的成肌细胞向成骨细胞的分化。高级糖基化终产物通过抑制该途径来抑制成骨细胞分化。

项目成果

Effects of a single injection of teriparatide on bone turnover barkers in postmenopausal women

单次注射特立帕肽对绝经后妇女骨转换指标的影响

• 发表时间: 2012
• 作者: Shiraki M; Sugimoto T; Nakamura T
• 通讯作者: Nakamura T

FAM5C is a soluble osteoblast differentiation factor linking muscle to bone

FAM5C 是一种连接肌肉和骨骼的可溶性成骨细胞分化因子

• 发表时间: 2012
• 作者: Tanaka K; Matsumoto E; Higashimaki Y; Sugimoto T; Seino S; Kaji H
• 通讯作者: Kaji H

Comparison of serum sclerostin levels among patients with postmenopausal osteoporosis, prmnary hyperparathyroidism and osteomalacia

绝经后骨质疏松症、原发性甲状旁腺功能亢进症及骨软化症患者血清硬化素水平比较

• 发表时间: 2011
• 作者: Kaji H; et al
• 通讯作者: et al

Effect of teriparatide on BMD and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture

特立帕肽对日本骨质疏松症骨折高危受试者 BMD 和骨转换标志物的影响

• 发表时间: 2010
• 影响因子: 4.1
• 作者: Miyauchi A; et al
• 通讯作者: et al

Advanced glycation end-products(AGEs), but not high glucose, inhibits the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression

晚期糖基化终末产物 (AGE)（而非高葡萄糖）通过抑制 osterix 表达来抑制小鼠基质 ST2 细胞的成骨细胞分化

• 发表时间: 2012
• 作者: Okazaki K et al