Regulation of osteoclastogenesis by transcriptional repressor Blimp1 via epigenetic regulation

转录抑制因子 Blimp1 通过表观遗传调控破骨细胞生成

• 批准号: 23592231
• 负责人: MIYAUCHI Yoshiteru
• 金额: $ 3.24万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592231/
• 关键词: 破骨細胞; 骨粗鬆症; 骨代謝; 転写因子

Osteoclasts are unique bone resorbing cells, and thus are therapeutic targets to treat bone diseases such as osteoporosis. We found that B lymphocyte induced maturation protein 1 (Blimp1), a transcriptional repressor, was required for osteoclastogenesis. Although Blimp1-null mutant mice are embryonic lethal, Blimp1 conditional knockout at an adult stage by a Cre/loxP system did not promote lethal adverse effects in mice, while resulted in significant inhibition of osteoclast formation with increased bone mass. Thus, Blimp1 was considered as a therapeutic target to treat skeletal diseases such as osteoporosis (J Biol Chem 2012).

破骨细胞是独特的骨吸收细胞，因此是治疗骨疾病如骨质疏松症的治疗靶点。我们发现，B淋巴细胞诱导成熟蛋白1（Blimp 1），一个转录抑制因子，是破骨细胞生成所必需的。虽然Blimp 1-null突变小鼠是胚胎致死的，但通过Cre/loxP系统在成年阶段敲除Blimp 1条件性基因不会促进小鼠的致死性不良反应，同时导致破骨细胞形成的显著抑制和骨量增加。因此，Blimp 1被认为是治疗骨质疏松症等骨骼疾病的治疗靶点（J Biol Chem 2012）。

项目成果

Matrix metalloproteinase 13 in the ligamentum flavum from lumbar spinal canal stenosis patients with and without diabetes mellitus

• DOI: 10.1007/s00776-011-0135-2
• 发表时间: 2011-11-01
• 期刊: JOURNAL OF ORTHOPAEDIC SCIENCE
• 影响因子: 1.7
• 作者: Cui, Guanyu;Watanabe, Kota;Matsumoto, Morio
• 通讯作者: Matsumoto, Morio

Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis

• DOI: 10.1002/jbmr.1634
• 发表时间: 2012-09-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Hoshi, Hiroko;Hao, Wu;Miyamoto, Takeshi
• 通讯作者: Miyamoto, Takeshi

An Essential Role for STAT6-STAT1 Protein Signaling in Promoting Macrophage Cell-Cell Fusion

• DOI: 10.1074/jbc.m112.358226
• 发表时间: 2012-09-21
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Miyamoto, Hiroya;Katsuyama, Eri;Miyamoto, Takeshi
• 通讯作者: Miyamoto, Takeshi

Suppressive effects for osteoclastogenesis regulated by RANKL signal.

RANKL 信号调节的破骨细胞生成的抑制作用。

• 发表时间: 2011
• 期刊: Clin Calcium.
• 作者: Miyauchi Y;Miyamoto T.
• 通讯作者: Miyamoto T.

転写抑制因子Blimp1は骨代謝制御の分子標的である

转录抑制因子 Blimp1 是调节骨代谢的分子靶标

• 发表时间: 2011
• 作者: 宮内芳輝;戸山芳昭;宮本健史
• 通讯作者: 宮本健史