Identification and functional analysis of a novel substrate of Pdk4 in the regulation of osteoclastogenesis in the unloaded condition

空载条件下调节破骨细胞生成的 Pdk4 新型底物的鉴定和功能分析

• 批准号: 24659829
• 负责人: KOMORI Toshihisa
• 金额: $ 2.41万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 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/en/grant/KAKENHI-PROJECT-24659829/
• 关键词: 骨細胞; 破骨細胞; 廃用性骨粗鬆症; メカニカルストレス; Pdk4

Bone mass is increase by exercise and reduced by long-term bed rest, immobilization caused by nerve injury, and microgravity in the space. These non-weight bearing conditions cause disuse osteoporosis. Osteocyte network, which is embedded in bone, is responsible for the sensing of mechanical stress and the transduction of the signal to osteoblasts and osteoclasts in the bone surface, and regulates bone mass. Pdk4, which is a kinase that inhibits energy production in mitochondria, was upregulated in osteoblasts and osteocytes in the unloaded condition of adult mice. Bone loss in the unloaded condition was not caused in Pdk4 adult knockout mice, indicating that Pdk4 is involved in bone loss in the unloaded condition of adult mice.

骨量因运动而增加，因长期卧床休息、神经损伤引起的固定和空间微重力而减少。这些非负重状况会导致失用性骨质疏松症。骨细胞网络嵌入骨中，负责感知机械应力并将信号传递给骨表面的成骨细胞和破骨细胞，调节骨量。Pdk4是一种抑制线粒体能量产生的激酶，在成年小鼠的空载条件下，成骨细胞和骨细胞中的Pdk4表达上调。在Pdk4基因敲除的成年小鼠中，未出现脱载状态下的骨质流失，说明Pdk4参与了成年小鼠脱载状态下的骨质流失。

项目成果

骨細胞ネットワークによるメカニカルストレス応答

骨细胞网络的机械应力响应

• 发表时间: 2013
• 作者: Masuyama R;Mizuno A;Komori H;Kajiya H;Uekawa A;Kitaura H;Okabe K;Ohyama K;Komori T;Nambu Y;Kagawa R;Tanaka K;Masuyama R;小守壽文
• 通讯作者: 小守壽文

Roles of Cbfb in bone development during embryonic stage and after birth

Cbfb 在胚胎期和出生后骨骼发育中的作用

• 发表时间: 2013
• 作者: Masuyama R;Mizuno A;Komori H;Kajiya H;Uekawa A;Kitaura H;Okabe K;Ohyama K;Komori T;Nambu Y;Kagawa R;Tanaka K;Masuyama R;小守壽文;小守壽文
• 通讯作者: 小守壽文

Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53-dependent apoptosis without enhancing proliferation

• DOI: 10.1038/onc.2013.130
• 发表时间: 2014-04-03
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Ito, K.;Maruyama, Z.;Komori, T.
• 通讯作者: Komori, T.

Roles of Cbfb in bone development during embryonic stage and after birth.

Cbfb 在胚胎期和出生后骨骼发育中的作用。

• 发表时间: 2013
• 作者: Masuyama R;Mizuno A;Komori H;Kajiya H;Uekawa A;Kitaura H;Okabe K;Ohyama K;Komori T;Nambu Y;Kagawa R;Tanaka K;Masuyama R;小守壽文;小守壽文;小守壽文;小守壽文;Toshihisa Komori;Toshihisa Komori;Toshihisa Komori
• 通讯作者: Toshihisa Komori

Proliferation, differentiation, and apoptosis in chondrocyte.

软骨细胞的增殖、分化和凋亡。

• 发表时间: 2013
• 作者: 大橋俊夫;河合佳子;Toshihisa Komori
• 通讯作者: Toshihisa Komori