Analysi of the role of cartducin, a novel growth factor secreted from cartilage, on bone development

软骨分泌的新型生长因子cartducin对骨发育的作用分析

• 批准号: 18592062
• 负责人: MAEDA Takashi
• 金额: $ 2.43万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592062/
• 关键词: cartducin; growth factor; chondrocytes; chondroprogenitor cells; bone development; MAP kinase; PI3 kinase; endothelial cells; PI3・キナーゼ

Several growth factors and hormones regulate bone development. However, the molecular mechanisms are not thoroughly understood. We previously identified novel secretory protein from cartilage, and named it "cartducin". Our recent studies cleared that cartducin promotes proliferation of chondroprogenitor cells and chondrocytes. In this project, we first examined whether cartducin exists in serum and further investigated the intracellular signaling pathways stimulated by cartducin in mesenchymal chondroprogenitor cells. Our first analysis showed that cartducin was undetectable in mouse serum. Next, chondroprogenitor cells were stimulated with cartducin, and three major groups of mitogen-activated protein kinase (MAPK) pathways and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway were examined. Cartducin activated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt, and inhibition of these pathways by specific inhibitors blocked cartducin-induced DNA synthesis in chon … More droprogenitor cells. These data suggest that cartducin is a peripheral skeletal growth factor, and the proliferation of mesenchymal chondroprogenitor cells stimulated by cartducin is associated with activations of the ERK1/2 and PI3K/Akt signaling pathways. Furthermore, we hypothesized that cartducin is an anti-angiogenic factor because cartducin was expressed in avascular zone of cartilage. Our further analysis showed that cartducin promoted proliferation and migration of mouse endothelial cells. Stimulation of these cells by cartducin led to activation of ERK1/2 and p38 MAPK. Inhibition of ERK1/2 or p38 MAPK pathways by specific inhibitors blocked the cartducin-induced endothelial cell proliferation, and migration was blocked by inhibition of ERK1/2, but not p38 MAPK pathway. These results suggest that cartducin may be involved as a novel angiogenic factor in bone development. Taken together, our study indicates that cartducin plays important roles in regulating bone development as both a growth factor and an angiogenic factor through specific signaling pathways. Less

几种生长因子和激素调节骨发育。然而，其分子机制尚未完全了解。我们以前从软骨中鉴定了一种新的分泌蛋白，并将其命名为“cartducin”。我们最近的研究表明，cartducin促进软骨祖细胞和软骨细胞的增殖。在本项目中，我们首先检测cartducin是否存在于血清中，并进一步研究cartducin在间充质软骨祖细胞中刺激的细胞内信号通路。我们的第一次分析表明，在小鼠血清中检测不到cartducin。接下来，用cartducin刺激软骨祖细胞，并检查三组主要的促分裂原活化蛋白激酶（MAPK）途径和磷脂酰肌醇3-激酶（PI 3 K）/Akt信号传导途径。Cartducin激活细胞外信号调节激酶1/2（ERK 1/2）和Akt，通过特异性抑制剂抑制这些途径可阻断Cartducin诱导的chon细胞DNA合成。 ...更多信息 前体细胞这些数据表明，cartducin是一种外周骨骼生长因子，并且由cartducin刺激的间充质软骨祖细胞的增殖与ERK 1/2和PI 3 K/Akt信号通路的激活相关。此外，我们假设cartducin是一种抗血管生成因子，因为cartducin在软骨的无血管区表达。我们的进一步分析表明，cartducin促进小鼠内皮细胞的增殖和迁移。cartducin刺激这些细胞导致ERK 1/2和p38 MAPK的激活。特异性抑制剂抑制ERK 1/2或p38 MAPK通路可阻断cartducin诱导的内皮细胞增殖，抑制ERK 1/2可阻断内皮细胞迁移，而抑制p38 MAPK通路则无作用。这些结果表明，cartducin可能参与作为一种新的血管生成因子在骨发育。总之，我们的研究表明，cartducin通过特定的信号通路作为生长因子和血管生成因子在调节骨发育中起重要作用。少

项目成果

CTRP3/cartducin promotes proliferation and migration of endothelial cells

• DOI: 10.1007/s11010-007-9506-6
• 发表时间: 2007-10-01
• 期刊: MOLECULAR AND CELLULAR BIOCHEMISTRY
• 影响因子: 4.3
• 作者: Akiyama, Hironori;Furukawa, Souhei;Maeda, Takashi
• 通讯作者: Maeda, Takashi

Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through both extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways

• DOI: 10.1111/j.1742-4658.2006.05240.x
• 发表时间: 2006-05-01
• 期刊: FEBS JOURNAL
• 影响因子: 5.4
• 作者: Akiyama, H;Furukawa, S;Maeda, T
• 通讯作者: Maeda, T

ClqTNFファミリー分泌蛋白CTRP3/cartducinの血管内皮細胞に対する増殖および遊走促進作用

ClqTNF家族分泌蛋白CTRP3/cartducin对血管内皮细胞增殖和迁移的促进作用

• 发表时间: 2007
• 作者: ○前田 隆史;脇坂 聡
• 通讯作者: 脇坂 聡

C1qTNFファミリー分泌蛋白CTRP3/cartducinの血管内皮細胞に対する増殖および遊走促進作用

C1qTNF家族分泌蛋白CTRP3/cartducin对血管内皮细胞增殖和迁移的促进作用

• 发表时间: 2007
• 作者: ○前田 隆史;脇坂 聡
• 通讯作者: 脇坂 聡

C1qTNF-related protein-3 (CTRP3)/cartducin promotes proliferation and Association migration of endothelial cells

C1qTNF 相关蛋白 3 (CTRP3)/cartducin 促进内皮细胞增殖和联合迁移

• 发表时间: 2007
• 作者: Maeda;T;Wakisaka;S
• 通讯作者: S