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

有几种生长因子和激素调节骨骼发育。然而，其分子机制尚不完全清楚。我们以前从软骨中发现了新的分泌蛋白，并将其命名为Cartducin。我们最近的研究表明，Cartducin促进软骨前体细胞和软骨细胞的增殖。在这个项目中，我们首先检测了血清中是否存在Cartducin，并进一步研究了Cartducin刺激间充质软骨前体细胞的细胞内信号通路。我们的第一个分析表明，在小鼠血清中检测不到Cartducin。接下来，用Cartducin刺激软骨前体细胞，检测三组主要的丝裂原活化蛋白激酶(MAPK)通路和磷脂酰肌醇3-激酶(PI3K)/Akt信号通路。Cartducin激活细胞外信号调节激酶1/2和Akt，并用特异性抑制剂抑制这些通路，阻断Cartducin诱导的…的DNA合成更多的直系祖细胞。这些结果提示Cartducin是一种外周骨骼生长因子，Cartducin刺激间充质软骨前体细胞增殖与ERK1/2和PI3K/Akt信号通路的激活有关。此外，我们假设Cartducin是一种抗血管生成因子，因为Cartducin在软骨无血管区表达。我们的进一步分析表明，Cartducin促进了小鼠内皮细胞的增殖和迁移。Cartducin刺激这些细胞后，ERK1/2和p38MAPK被激活。特异性抑制剂抑制ERK1/2或p38MAPK通路可阻断Cartducin诱导的内皮细胞增殖，并通过抑制ERK1/2而不是p38MAPK通路阻止迁移。这些结果提示Cartducin可能作为一种新的血管生成因子参与骨发育。综上所述，我们的研究表明，Cartducin作为一种生长因子和一种血管生成因子，通过特定的信号通路在调节骨骼发育中发挥着重要作用。较少

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