Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through both extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways
Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through both extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways
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DOI：
10.1111/j.1742-4658.2006.05240.x
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发表时间：
2006-05-01
期刊：
影响因子：
5.4
通讯作者：
Maeda, T
中科院分区：
文献类型：
--
作者：
Akiyama, H;Furukawa, S;Maeda, T
Cartducin是Acrp 30/adiponectin的副产物，是软骨形成前体和增殖软骨细胞产生的分泌蛋白，属于C1 q蛋白家族。我们最近发现cartducin在体外促进间充质软骨祖细胞和软骨肉瘤衍生的软骨细胞的生长。然而，负责调节细胞增殖的cartducin信号通路尚未被记录。在这项研究中，我们检查了cartducin是否存在于血清中，并进一步研究了cartducin在间充质软骨祖细胞中刺激的细胞内信号通路。蛋白质印迹分析表明，与Acrp 30/脂联素不同，cartducin在小鼠血清中检测不到。接下来，用cartducin刺激间充质软骨祖细胞N1511细胞，并检查三组主要的促分裂原活化蛋白激酶（MAPK）通路和磷脂酰肌醇3-激酶（PI 3 K）/Akt信号通路。Cartducin激活细胞外信号调节激酶1/2（ERK 1/2）和Akt，但不激活c-jun N-末端激酶（JNK）和p38 MAPK。MEK 1/2抑制剂U 0126可阻断cartducin诱导的N1511细胞ERK 1/2磷酸化，抑制cartducin诱导的DNA合成。PI 3 K抑制剂LY 294002阻断了N1511细胞中cartducin刺激的Akt磷酸化，并观察到cartducin诱导的DNA合成减少。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。
Cartducin, a paralog of Acrp30/adiponectin, is a secretory protein produced by both chondrogenic precursors and proliferating chondrocytes, and belongs to a novel C1q family of proteins. We have recently shown that cartducin promotes the growth of both mesenchymal chondroprogenitor cells and chondrosarcoma-derived chondrocytic cells in vitro. However, the cartducin-signaling pathways responsible for the regulation of cell proliferation have not been documented. In this study, we examined whether cartducin exists in serum and further investigated the intracellular signaling pathways stimulated by cartducin in mesenchymal chondroprogenitor cells. Western blot analysis showed that, unlike Acrp30/adiponectin, cartducin was undetectable in mouse serum. Next, mesenchymal chondroprogenitor N1511 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, but not c-jun N-terminal kinase (JNK) nor p38 MAPK. The MEK1/2 inhibitor, U0126, blocked cartducin-stimulated ERK1/2 phosphorylation and suppressed the DNA synthesis induced by cartducin in N1511 cells. The PI3K inhibitor, LY294002, blocked cartducin-stimulated Akt phosphorylation and a decrease in cartducin-induced DNA synthesis in N1511 cells was also observed. These data suggest that cartducin is a peripheral skeletal growth factor, and that the proliferation of mesenchymal chondroprogenitor cells stimulated by cartducin is associated with activations of the ERK1/2 and PI3K/Akt signaling pathways.