Analysis of osteoclast niche regulated by Wnt signals.

Wnt信号调控的破骨细胞生态位分析。

• 批准号: 22390351
• 负责人: TAKAHASHI Naoyuki
• 金额: $ 12.31万
• 依托单位: Matsumoto Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-22390351/
• 关键词: 口腔生化学; 破骨細胞; 骨芽細胞; Ｗｎｔ; IL-34; 破骨細胞前駆細胞; 破骨細胞ニッチ; Wnt5a; Ror2; Wnt非古典経路; OPG; RANKL; M-CSF

We examined the role of Wnt signaling for the formation of osteoclast niche, and the results as follows. (1) The osteoclast niche was analyzed and characteristics of osteoclast precursors (quiescent osteoclast precursors, QOP) were clarified. (2) The role of noncanonical Wnt signaling in osteoclastogenesis was examined. Noncanonical Wnt signals (Wnt5a-Ror2 signals) were shown to play important roles in osteoclastogenesis. (3) Wnt5a-Ror2 signals enhanced RANKexpression in QOPs. Canonical Wnt signals did not appear to play a role in osteoclastogenesis. (4) GeneChip analysis was performed on QOPs to identify specific markers of QOPs. But we failed to isolate specific markers of QOPs. However, we found that osteoclasts specifically express Wnt5a.(5) IL-34 was identified as an important cytokine for generation of QOP in hematopoietic tissues. (6) Alveolar bone loss was examined in OPG-deficient (OPG?/?) mice and RANKL-overexpressing transgenic mice. OPG?/? mice were shown to be a use l model of periodontitis. (7) Administration of soluble form of Ror2 into collagen-induced arthritis mice effectively suppressed bone destruction.

我们检测了Wnt信号在破骨细胞龛形成中的作用，结果如下。(1)分析破骨细胞生态位，明确破骨细胞前体细胞（静止破骨细胞前体细胞，QOP）特征。(2)研究了非经典Wnt信号在破骨细胞生成中的作用。非经典Wnt信号（Wnt 5a-Ror 2信号）在破骨细胞发生中起重要作用。(3)Wnt 5a-Ror 2信号增强QOP中的RANK表达。典型的Wnt信号似乎在破骨细胞生成中没有发挥作用。(4)对QOP进行基因芯片分析以鉴定QOP的特异性标志物。但我们未能分离出QOP的特定标记。然而，我们发现破骨细胞特异性表达Wnt 5a。(5)IL-34被鉴定为造血组织中产生QOP的重要细胞因子。(6)在OPG缺乏（OPG？/？）小鼠和RANKL过表达转基因小鼠。OPG？/？小鼠被证明是牙周炎的有用模型。(7)将可溶性形式的Ror 2给予胶原诱导的关节炎小鼠有效地抑制了骨破坏。

项目成果

Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis

成骨细胞和破骨细胞前体之间的 Wnt5a-Ror2 信号传导增强破骨细胞生成

• 发表时间: 2012
• 期刊: Nat. Med
• 作者: Maeda;K.;Kobayashi;Y.;Udagawa;N.;(省略7名);Nishita;M.;Marumo;K.;Martin;T. J.;Minami;Y.;Takahashi;N.
• 通讯作者: N.

Noncanonical Wnt signaling and osteoclastogenesis

非经典 Wnt 信号传导和破骨细胞生成

• 发表时间: 2010
• 作者: Kobayashi Y;Maeda K;Uehara S;Yamashita T;Takahashi N;高橋直之;高橋直之;高橋直之;高橋直之;Naoyuki Takahashi;Naoyuki Takahashi;高橋直之;高橋直之;高橋直之;高橋直之;高橋直之;Naoyuki Takahashi;Naoyuki Takahashi;高橋直之;高橋直之;Naoyuki Takahashi;Naoyuki Takahashi
• 通讯作者: Naoyuki Takahashi

破骨細胞の分化を調節する骨芽 細胞の新しい役割

成骨细胞在调节破骨细胞分化中的新作用

• 发表时间: 2012
• 作者: Kobayashi Y;Maeda K;Uehara S;Yamashita T;Takahashi N;高橋直之;高橋直之
• 通讯作者: 高橋直之

破骨細胞形成を調節する骨芽細 胞の新しい役割

成骨细胞在调节破骨细胞形成中的新作用

• 发表时间: 2010
• 作者: Kobayashi Y;Maeda K;Uehara S;Yamashita T;Takahashi N;高橋直之;高橋直之;高橋直之;高橋直之;Naoyuki Takahashi;Naoyuki Takahashi;高橋直之;高橋直之;高橋直之;高橋直之;高橋直之;Naoyuki Takahashi;Naoyuki Takahashi;高橋直之;高橋直之
• 通讯作者: 高橋直之

Function of OPG as a Traffic Regulator for RANKL Is Crucial for Controlled Osteoclastogenesis

• DOI: 10.1002/jbmr.89
• 发表时间: 2010-09-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Aoki, Shigeki;Honma, Masashi;Suzuki, Hiroshi
• 通讯作者: Suzuki, Hiroshi