The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity
The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity
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DOI：
10.3109/s10165-006-0524-0
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发表时间：
2006-12
影响因子：
2.2
通讯作者：
T. Miyamoto
中科院分区：
文献类型：
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作者：
T. Miyamoto
破骨细胞是骨吸收细胞，在类风湿性关节炎的骨破坏中起关键作用。众所周知，破骨细胞通过单核破骨细胞的细胞-细胞融合形成多核细胞;然而，破骨细胞细胞-细胞融合需要哪些分子，以及多核化的作用仍然没有得到表征。我们确定了树突状细胞特异性跨膜蛋白DC-STAMP，一个假定的七个跨膜蛋白，并产生DC-STAMP缺陷小鼠。在DC-STAMP缺陷小鼠中，破骨细胞的细胞融合被完全废除，而破骨细胞分化或破骨细胞成熟标志物所需的转录因子被诱导为野生型破骨细胞。有趣的是，与野生型破骨细胞相比，DC-STAMP缺陷型破骨细胞的骨吸收活性降低，DC-STAMP缺陷型小鼠表现出骨硬化症。因此，我们确定DC-STAMP作为破骨细胞-细胞融合的必要分子，并发现多核破骨细胞具有比DC-STAMP缺陷小鼠中所见的单核破骨细胞更高的骨吸收活性。
Osteoclasts are bone-resorbing cells that play a critical role for bone destruction in rheumatoid arthritis. It is well known that osteoclasts form multinuclear cells by cell–cell fusion of mononuclear osteoclasts; however, what molecules are required for osteoclast cell–cell fusion, and the role of multinucleation remain uncharacterized. We identified the dendritic cell-specific transmembrane protein DC-STAMP, a putative seven transmembrane protein, and generated DC-STAMP-deficient mice. The cell fusion of osteoclasts was completely abrogated in DC-STAMP-deficient mice, while the transcription factors required for osteoclast differentiation or osteoclast maturation markers were induced as wild type osteoclasts. Interestingly, bone-resorbing activity was reduced in DC-STAMP-deficient osteoclasts compared with wild-type osteoclasts, and DC-STAMP-deficient mice showed osteopetrosis. Thus, we identified DC-STAMP as an essential molecule for osteoclast cell–cell fusion, and found that multinuclear osteoclasts have a higher bone-resorbing activity than mononuclear osteoclastic cells seen in DC-STAMP-deficient mice.