Pannexin 3 Inhibits Proliferation of Osteoprogenitor Cells by Regulating Wnt and p21 Signaling
Pannexin 3 Inhibits Proliferation of Osteoprogenitor Cells by Regulating Wnt and p21 Signaling
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DOI：
10.1074/jbc.m113.523241
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发表时间：
2014-01-31
影响因子：
4.8
通讯作者：
Yamada, Yoshihiko
中科院分区：
文献类型：
--
作者：
Ishikawa, Masaki;Iwamoto, Tsutomu;Yamada, Yoshihiko
背景：骨祖细胞从增殖向分化转化的机制尚不清楚。结果：Panx 3通过阻断经典Wnt信号通路和促进p21激活抑制骨祖细胞增殖。结论：Panx 3半通道可诱导多条对细胞周期退出至关重要的Panx 3信号通路。意义：我们的研究结果表明，Panx 3是骨祖细胞从增殖到分化的一个新的调控因子，经典的Wnt信号和BMP分别促进骨祖细胞的增殖和分化。然而，从增殖到分化的过渡所涉及的调控机制尚不清楚。在这里，我们发现Panx 3（pannexin 3）通过抑制增殖和促进细胞周期退出在这一转变中起着关键作用。使用原代颅骨细胞和外植体，C3 H10 T12细胞和C2 C12细胞，我们发现Panx 3表达抑制细胞生长，而内源性Panx 3表达的抑制增加了它。我们还发现Panx 3半通道通过促进GSK 3激活的β-catenin降解来抑制细胞生长。此外，Panx 3半通道通过减少cAMP/PKA/CREB信号传导抑制细胞周期蛋白D1转录和Rb磷酸化。此外，Panx 3内质网Ca ~（2+）通道通过钙调素/Smad途径诱导p21的转录和磷酸化，从而导致细胞周期退出。我们的研究结果表明，Panx 3是一种新的调节剂，通过多种Panx 3信号通路促进骨祖细胞从增殖到分化的转变。
Background: The mechanism of the transition from osteoprogenitor cell proliferation to differentiation is unclear. Results: Panx3 inhibits osteoprogenitor proliferation by blocking canonical Wnt signaling and promoting p21 activation. Conclusion: A Panx3 hemichannel induces multiple Panx3 signaling pathways critical for the cell cycle exit. Significance: Our findings reveal that Panx3 is a new regulator to switch the stage from proliferation to differentiation in osteoprogenitor cells.Canonical Wnt signaling and BMP promote the proliferation and differentiation of osteoprogenitors, respectively. However, the regulatory mechanism involved in the transition from proliferation to differentiation is unclear. Here, we show that Panx3 (pannexin 3) plays a key role in this transition by inhibiting the proliferation and promoting the cell cycle exit. Using primary calvarial cells and explants, C3H10T1/2 cells, and C2C12 cells, we found that Panx3 expression inhibited cell growth, whereas the inhibition of endogenous Panx3 expression increased it. We also found that the Panx3 hemichannel inhibited cell growth by promoting -catenin degradation through GSK3 activation. Additionally, the Panx3 hemichannel inhibited cyclin D1 transcription and Rb phosphorylation through reduced cAMP/PKA/CREB signaling. Furthermore, the Panx3 endoplasmic reticulum Ca2+ channel induced the transcription and phosphorylation of p21, through the calmodulin/Smad pathway, and resulted in the cell cycle exit. Our results reveal that Panx3 is a new regulator that promotes the switch from proliferation to differentiation of osteoprogenitors via multiple Panx3 signaling pathways.