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Apatite-mediated actin dynamics in resorbing osteoclasts

机译:磷灰石介导的肌动蛋白动力学在破骨细胞吸收中的作用

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摘要

The actin cytoskeleton is essential for osteoclasts main function, bone resorption. Two different organizations of actin have been described in osteoclasts, the podosomes belt corresponding to numerous F-actin columns arranged at the cell periphery, and the sealing zone defined as a unique large band of actin. To compare the role of these two different actin organizations, we imaged osteoclasts on various substrata: glass, dentin, and apatite. Using primary osteoclasts expressing GFP-actin, we found that podosome belts and sealing zones, both very dynamic actin structures, were present in mature osteoclasts; podosome belts were observed only in spread osteoclasts adhering onto glass, whereas sealing zone were seen in apico-basal polarized osteoclasts adherent on mineralized matrix. Dynamic observations of several resorption cycles of osteoclasts seeded on apatite revealed that 1) podosomes do not fuse together to form the sealing zone; 2) osteoclasts alternate successive stationary polarized resorption phases with a sealing zone and migration, nonresorption phases without any specific actin structure; and 3) apatite itself promotes sealing zone formation though c-src and Rho signaling. Finally, our work suggests that apatite-mediated sealing zone formation is dependent on both c-src and Rho whereas apico-basal polarization requires only Rho.
机译:肌动蛋白的细胞骨架对于破骨细胞的主要功能,骨吸收至关重要。破骨细胞中已经描述了两种不同的肌动蛋白组织:足小体带对应于排列在细胞外围的许多F-肌动蛋白柱,密封区域定义为独特的肌动蛋白大带。为了比较这两种不同的肌动蛋白组织的作用,我们对破骨细胞成像在各种基质上:玻璃,牙本质和磷灰石。使用表达GFP-肌动蛋白的原代破骨细胞,我们发现成熟的破骨细胞中存在足突带和密封区,它们都是非常动态的肌动蛋白结构。仅在附着在玻璃上的散布破骨细胞中观察到了足突带,而在粘附在矿化基质上的apico基底极化的破骨细胞中观察到了密封区。动态观察观察接种在磷灰石上的破骨细胞的几个吸收周期,发现:1)囊泡不融合在一起形成密封区; 2)破骨细胞交替的连续的固定极化吸收相具有密封区域,而迁移,非吸收相没有任何特定的肌动蛋白结构; 3)磷灰石本身通过c-src和Rho信号促进密封区域的形成。最后,我们的工作表明,磷灰石介导的密封带的形成取决于c-src和Rho,而apico-基础极化仅需要Rho。

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