Physiological function of Integrin in mechanical response of bone

整合素在骨机械反应中的生理作用

• 批准号: 24790398
• 负责人: KANEKO Keiko
• 金额: $ 2.83万
• 依托单位: National Center for Geriatrics and Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790398/
• 关键词: 骨代謝; 骨芽細胞; 骨細胞; インテグリン; 遺伝子改変マウス; シグナル伝達; 細胞骨格; シアストレス; ノックアウトマウス; YAP; ずり応力

Osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone. However, the identity of the mechano-receptor and downstream mechno signaling pathways remain largely unknown. Using primary osteoblastic cells mechanically stimulated with fluid shear stress, an intracellular kinase cascade involving c-Src, p130Cas and JNK was identified the downstream of integrin alpha-v. Mice deficient in integrin alpha-v in the osteoblast lineage exhibited an impaired skeletal response to ulnar loading, in terms of Sost expression, pointing to the role of integrin alpha-v in mechano-sensing in vivo. Thus, integirn alpha-v may be integral to a mechanosensing machinery in osteoblast lineage cells and involved in the activation of a Src-JNK-YAP/TAZ pathway in response to mechanical stimulation.

成骨细胞系细胞，尤其是骨细胞，被认为是骨中最主要的机械感觉细胞。然而，机械受体和下游机制信号通路的特性在很大程度上仍然不清楚。利用流体剪切力机械刺激原代成骨细胞，在整合素α-v下游发现了一个涉及c-Src、p130Cas和JNK的细胞内激酶级联。在成骨细胞系中，整合素α-v缺乏的小鼠表现出对尺骨负荷的骨骼反应受损，在SOST表达方面，表明整合素α-v在体内的机械感觉中的作用。因此，整合素α-v可能是成骨细胞系细胞机械传感机制的组成部分，并参与机械刺激下Src-JNK-YAP/TAZ通路的激活。

项目成果

Integrin αv in the mechanical response of osteoblast lineage cells.

• DOI: 10.1016/j.bbrc.2014.04.006
• 发表时间: 2014-05-02
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Kaneko, Keiko;Ito, Masako;Naoe, Yoshinori;Lacy-Hulbert, Adam;Ikeda, Kyoji
• 通讯作者: Ikeda, Kyoji

Integrin alpha-v and mechano signal transduction in osteoblast lineage cells

成骨细胞谱系细胞中的整合素α-V和机械信号转导

• 发表时间: 2013
• 作者: Keiko Kaneko;Masako Ito;Adam Lacy-Hulbert;Kyoji Ikeda
• 通讯作者: Kyoji Ikeda

Integrinαv and mechano signal transduction in osteoblast lineage cells

成骨细胞谱系细胞中的整合素αv和机械信号转导

• 发表时间: 2013
• 作者: Keiko Kaneko;Masako Ito;Adam Lacy-Hulbert;Kyoji Ikeda
• 通讯作者: Kyoji Ikeda