DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells.
DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells.
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DOI：
10.1084/jem.20050645
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发表时间：
2005-08-01
期刊：
影响因子：
--
通讯作者：
Suda T
中科院分区：
文献类型：
--
作者：
Yagi M;Miyamoto T;Sawatani Y;Iwamoto K;Hosogane N;Fujita N;Morita K;Ninomiya K;Suzuki T;Miyamoto K;Oike Y;Takeya M;Toyama Y;Suda T
破骨细胞是骨吸收细胞，在骨重塑中发挥关键作用。破骨细胞通过单核破骨细胞的融合形成大的多核巨细胞。然而，细胞融合是如何介导的尚不清楚。我们通过多核破骨细胞和单核巨噬细胞之间的 DNA 减法筛选，鉴定了树突状细胞特异性跨膜蛋白 (DC-STAMP)，一种假定的七次跨膜蛋白。 DC-STAMP 在破骨细胞中高表达，但在巨噬细胞中不表达。产生了 DC-STAMP 缺陷小鼠，尽管破骨细胞标记物和细胞骨架结构表达正常，但纯合子中的破骨细胞细胞融合完全被消除。由于破骨细胞多核通过逆转录病毒引入 DC-STAMP 得以恢复，细胞融合的丧失直接归因于 DC-STAMP 的缺乏。破骨细胞多核缺陷会降低骨吸收活性，导致石骨症。与破骨细胞类似，巨噬细胞融合形成的异物巨细胞在 DC-STAMP 缺陷小鼠中也被完全消除。因此，我们确定了破骨细胞和巨噬细胞融合的重要调节剂 DC-STAMP，以及破骨细胞多核在骨稳态中的重要作用。
Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell–specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP–deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP–deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.
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影响因子：
4
作者：
de Vries, TJ;Schoenmaker, T;Everts, V
通讯作者：
Everts, V
DOI：
10.1084/jem.190.12.1741
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
通讯作者：
Suda T
影响因子：
4
作者：
Faccio, R;Zou, W;Ross, FP
通讯作者：
Ross, FP
影响因子：
5.3
作者：
Saginario, C;Sterling, H;Vignery, A
通讯作者：
Vignery, A
影响因子：
4.8
作者：
Han, X;Sterling, H;Vignery, A
通讯作者：
Vignery, A