Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes
Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes
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DOI：
10.1242/dev.052324
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发表时间：
2011-01-15
期刊：
影响因子：
4.6
通讯作者：
Dudley, Andrew T.
中科院分区：
文献类型：
--
作者：
Li, Yuwei;Ahrens, Molly J.;Dudley, Andrew T.
对于在整个胚胎发生过程中发育并进入出生后生命的组织，产生分化细胞以促进组织生长与维持干细胞/祖细胞群体以保持未来生长潜力的要求不一致。在生长板软骨中，这种平衡部分是通过建立增殖期来实现的，该增殖期在终末分化成肥大软骨细胞之前扩增祖细胞的数量。在这里，我们表明，内源性钙/钙调蛋白依赖性蛋白激酶II（CamkII，也称为Camk 2）的活性上调前肥大和CamkII功能的损失基本上阻止从增殖到肥大的过渡。Wnt信号和Pthrp诱导的磷酸酶活性负调控CamkII活性。这种抑制的释放导致多种效应子途径的激活，包括Runx 2和β-连环蛋白依赖性途径。我们提出了一个综合模型的调节增殖潜力的CamkII活性，具有重要意义的生长控制和成人祖细胞/干细胞群体的研究。
For tissues that develop throughout embryogenesis and into postnatal life, the generation of differentiated cells to promote tissue growth is at odds with the requirement to maintain the stem cell/progenitor cell population to preserve future growth potential. In the growth plate cartilage, this balance is achieved in part by establishing a proliferative phase that amplifies the number of progenitor cells prior to terminal differentiation into hypertrophic chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein kinase II (CamkII, also known as Camk2) activity is upregulated prior to hypertrophy and that loss of CamkII function substantially blocks the transition from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase activity negatively regulate CamkII activity. Release of this repression results in activation of multiple effector pathways, including Runx2- and beta-catenin-dependent pathways. We present an integrated model for the regulation of proliferation potential by CamkII activity that has important implications for studies of growth control and adult progenitor/stem cell populations.