Conditioned Medium of Wnt/β-Catenin Signaling-Activated Olfactory Ensheathing Cells Promotes Synaptogenesis and Neurite Growth In Vitro
Conditioned Medium of Wnt/β-Catenin Signaling-Activated Olfactory Ensheathing Cells Promotes Synaptogenesis and Neurite Growth In Vitro
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DOI：
10.1007/s10571-013-9966-z
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发表时间：
2013-07
影响因子：
4
通讯作者：
Zhenyu Yang;Yin Wu;Lianhe Zheng;Chen Zhang;Jialei Yang;Ming Shi;Dongyun Feng;Zhong-liang Wu;Ya-zhou Wang
中科院分区：
文献类型：
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作者：
Zhenyu Yang;Yin Wu;Lianhe Zheng;Chen Zhang;Jialei Yang;Ming Shi;Dongyun Feng;Zhong-liang Wu;Ya-zhou Wang
嗅鞘细胞（OEC）是嗅觉系统中的主要神经胶质细胞，因其促进轴突生长和再生的能力而被广泛研究。它是否可以促进突触发生是一个重要的问题，但仍然是一个悬而未决的问题。我们已经鉴定出 Wnt 信号激活的 OEC 亚群，其在嗅球中的时空分布表明这些细胞在轴突生长和突触发生中发挥作用。在本研究中，我们在体外探索了这种可能性。主要培养 OEC，其中 Wnt 信号传导通过过度表达 β-catenin 激活，并通过显性失活 TCF4 抑制。通过将神经元与对照 OEC (cOECs CM)、Wnt/β-连环蛋白信号激活 OEC (wOECs CM) 或 Wnt 信号抑制 OEC (wiOEC) 的条件培养基共培养来评估神经突生长和突触发生。结果表明，虽然cOECs CM促进轴突生长，但wOECs CM表现出比cOECs CM更强的轴突生长促进作用。更重要的是，wOECs CM 刺激突触发生，突触素的表达和全细胞膜片钳记录证明了这一点。相反，cOEC CM 和 wiOEC CM 都不影响突触发生。我们的数据首次证明，与常规培养的 OEC 相比，wOEC CM 在增强轴突生长方面更有效，并且可能通过分泌因子促进突触发生。这些结果表明 wOEC 在治疗脊髓损伤方面具有潜在的应用。
Olfactory ensheathing cells (OECs), the major glia cells in the olfactory system, have been extensively studied because of their ability to promote axonal growth and regeneration. Whether it could facilitate synaptogenesis is an important, but remains as yet an unanswered question. We have identified a subgroup of Wnt signaling-activated OECs, spatiotemporal distribution of which in the olfactory bulb suggests a role for these cells in both axonal growth and synaptogenesis. In the present study, we explored this possibility in vitro. OECs were primarily cultured, in which Wnt signaling was activated by overexpressing β-catenin, and inhibited by dominant negative TCF4. Neurite growth and synaptogenesis were assessed by co-culturing neurons with conditioned medium from control OECs (cOECs CM), Wnt/β-catenin signaling-activated OECs (wOECs CM), or Wnt signaling-inhibited OECs (wiOECs). The results showed that although cOECs CM enhances axonal growth, wOECs CM exhibited a stronger axonal growth-promoting effect, than cOECs CM. More importantly, wOECs CM stimulates synatpogenesis, demonstrated by the expression of Synaptophysin and whole-cell patch clamp recording. In contrast, both cOECs CM and wiOECs CM do not affect synaptogenesis. Our data, for the first time, demonstrated that, in comparison with regularly cultured OECs, wOECs CM are more effective in enhancing axonal growth, and can promote synaptogenesis, probably by secreting factors. These results suggest a potential application of wOECs for treating spinal cord injury.