Tunneling nanotube formation is essential for the regulation of osteoclastogenesis
Tunneling nanotube formation is essential for the regulation of osteoclastogenesis
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DOI：
10.1002/jcb.24433
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发表时间：
2013-06
影响因子：
4
通讯作者：
Akira Takahashi;A. Kukita;Yin-Ji Li;Jingqi Zhang;H. Nomiyama;T. Yamaza;Y. Ayukawa;K. Koyano
中科院分区：
文献类型：
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作者：
Akira Takahashi;A. Kukita;Yin-Ji Li;Jingqi Zhang;H. Nomiyama;T. Yamaza;Y. Ayukawa;K. Koyano
破骨细胞是单核破骨细胞前体细胞融合形成的多核巨细胞。尽管发现了几种涉及DC - STAMP的膜蛋白作为破骨细胞前体融合所需的调节蛋白，但有关这一过程的细胞和分子事件仍然不明确。在这里，我们发现隧道纳米管（TNTs）是细胞融合之前破骨细胞前体之间细胞间通信的基本细胞结构，它是直径小的长细胞间桥。TNT的形成与破骨细胞的形成高度相关，并伴随着M - Sec基因的显著诱导，该基因是TNT形成的重要基因。在破骨细胞前体细胞中，RANKL可显著上调M - Sec基因的表达。用Latrunclin B或M - Sec siRNA阻断TNT的形成可显著抑制破骨细胞的发生。我们不仅发现了DiI标记的膜磷脂，还发现了DC - STAMP - GFP融合蛋白在破骨细胞发生过程中通过在破骨细胞前体中形成的tnt快速细胞间转运。这种调节分子通过tnt的运输对于破骨细胞前体之间的特异性细胞融合过程至关重要。j .细胞。中国生物医学工程学报，2014,31(2):387 - 398。©2012 Wiley期刊公司
Osteoclasts are the multinucleated giant cells formed by cell fusion of mononuclear osteoclast precursors. Despite the finding of several membrane proteins involving DC‐STAMP as regulatory proteins required for fusion among osteoclast precursors, cellular and molecular events concerning this process are still ambiguous. Here we identified Tunneling Nanotubes (TNTs), long intercellular bridges with small diameters, as the essential cellular structure for intercellular communication among osteoclast precursors in prior to cell fusion. Formation of TNTs was highly associated with osteoclastogenesis and it was accompanied with the significant induction of the M‐Sec gene, an essential gene for TNT formation. M‐Sec gene expression was significantly upregulated by RANKL‐treatment in osteoclast precursor cell line. Blockage of TNT formation by Latrunclin B or by M‐Sec siRNA significantly suppressed osteoclastogenesis. We have detected the rapid intercellular transport of not only the membrane phospholipids labeled with DiI but also the DC‐STAMP‐GFP fusion protein through TNTs formed among osteoclast precursors during osteoclastogenesis. Transportation of such regulatory molecules through TNTs would be essential for the process of the specific cell fusion among osteoclast precursors. J. Cell. Biochem. 114: 1238–1247, 2013. © 2012 Wiley Periodicals, Inc.