Cell adhesion signals regulate RANK expression in osteoclast precursors.

细胞粘附信号调节破骨细胞前体中的 RANK 表达。

• 批准号: 20791362
• 负责人: MOCHIZUKI Ayako
• 金额: $ 2.66万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20791362/
• 关键词: 破骨細胞; 分化; 接着シグナル; RANK; マクロファージ; 細胞接着; 遺伝子発現

The cells of monocyte/macrophage lineage differentiated into osteoclasts following the stimulation of cells with RANKL. It has been reported that cell adhesion signals are required for osteoclast differentiation from their precursors. However, details of the mechanism by which cell adhesion signals induce osteoclast differentiation have not been examined yet. In the present study, we investigated that cell adhesion signals participate in RANK expression in osteoclast precursors. Mouse bone marrow-derived macrophages (BMMs) were cultured on the culture dishes (the adherent condition) or on the methylcellulose gel (the non-adherent condition), and then examined osteoclast differentiation, activation of intracellular signals, and changes in gene expression. When BMMs were cultured under adherent condition, almost all BMMs differentiated into osteoclasts in response to RANKL stimulation. However, under non-adherent condition, the efficiency of osteoclast differentiation was markedly reduced even in the presence of RANKL. Although LPS or TNF-alpha activated the NF-kappa B-mediated signaling pathways under both conditions, RANKL failed to activate these pathways under non-adherent condition. We elucidated that mRNA and protein of RANK are highly expressed under adherent condition, and then accelerated by stimulation of RANKL. The inhibition of differentiation under non-adherent condition was recovered by overexpression of RANK or TRAF6. These results suggest that cell adhesion signals play an important role in regulating RANK expression in osteoclast precursors.

单核/巨噬细胞系细胞在RANKL刺激下向破骨细胞分化。据报道，细胞粘附信号是破骨细胞从其前体分化所必需的。然而，细胞粘附信号诱导破骨细胞分化的机制细节尚未被研究。在本研究中，我们研究了细胞粘附信号参与破骨细胞前体中RANK的表达。将小鼠骨髓源性巨噬细胞（BMMs）分别培养在培养皿（贴壁条件）和甲基纤维素凝胶（非贴壁条件）上，观察破骨细胞分化、细胞内信号激活和基因表达的变化。在贴壁条件下培养bmm时，几乎所有bmm在RANKL刺激下都分化为破骨细胞。然而，在非贴壁条件下，即使有RANKL存在，破骨细胞的分化效率也明显降低。尽管LPS或tnf - α在两种条件下都激活了NF-kappa b介导的信号通路，但在非贴壁条件下，RANKL未能激活这些通路。我们发现RANK的mRNA和蛋白在贴壁条件下高度表达，然后在RANKL的刺激下加速表达。非贴壁条件下的分化抑制通过过表达RANK或TRAF6恢复。这些结果表明，细胞粘附信号在调节破骨细胞前体的RANK表达中起重要作用。

项目成果

TGF-βはBMP-2による異所性骨形成を協力に促進する

TGF-β通过BMP-2协同促进异位骨形成

• 发表时间: 2009
• 作者: 舘慶太;高見正道;佐藤華;本田義知;宮本阿礼;望月文子;井上富雄;新谷悟;中村雅典;鈴木治;馬場一美;上條竜太郎
• 通讯作者: 上條竜太郎

Osteoclast differentiation induced by synthetic octacalcium phosphate through receptor activator of NF- kappa B ligand expression in osteoblasts

合成磷酸八钙通过成骨细胞中 NF-κ B 配体表达的受体激活剂诱导破骨细胞分化

• 发表时间: 2009
• 期刊: Tissue Engineering, Part A 15
• 作者: Takami M;Mochizuki A;Yamada A;Tachi K;Zhao B;Miyamoto Y;Anada T;Honda Y;Inoue T;Nakamura M;Suzuki O;Kamijo R:(T.M.;A.M. contributed equally to this work. )
• 通讯作者: A.M. contributed equally to this work. )

rigeminal sensory neurons in developing rats

发育中的大鼠的边缘感觉神经元

• 发表时间: 2009
• 作者: Inoue T;Nakayama K;Mochizuki A;Nakamura S;Shioda S
• 通讯作者: Shioda S

ラットにおける顔面神経核背側網様体から三叉神経運動ニューロンへのシナプス入力

大鼠面核背侧网状结构到三叉神经运动神经元的突触输入

• 发表时间: 2008
• 作者: 玄番晶子;中村史朗;望月文子;井上富雄
• 通讯作者: 井上富雄

PROPERTIES OF SYNAPTIC TRANSMISSION FROM THE RETICULAR FORMATION DORSAL TO THE FACIAL NUCLEUS TO TRIGEMINAL MOTONEURONS DURING EARLY POSTNATAL DEVELOPMENT IN RATS

• DOI: 10.1016/j.neuroscience.2009.12.065
• 发表时间: 2010-03-31
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Gemba-Nishimura, A.;Inoue, T.;Yoshimura, S.
• 通讯作者: Yoshimura, S.