RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis
RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis
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DOI：
10.1006/bbrc.1998.9788
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发表时间：
1998-12-18
影响因子：
3.1
通讯作者：
Higashio, K
中科院分区：
文献类型：
--
作者：
Nakagawa, N;Kinosaki, M;Higashio, K
破骨细胞分化因子（ODF）是破骨细胞生成抑制因子/骨保护素（OCIF/OPG）的配体，介导破骨细胞生成的重要信号。可溶性ODF直接与破骨细胞祖细胞结合，表明细胞上存在ODF的膜结合受体（ODFR）。为了了解ODF介导的破骨细胞发生的信号转导机制，我们从小鼠巨噬细胞样破骨细胞祖细胞系C7中克隆了ODF受体。核苷酸序列分析显示ODFR与RANK相同，RANK是最近鉴定的肿瘤坏死因子受体（TNFR）家族的成员，其参与树突状细胞功能的调节。相比之下;基因工程的可溶性RANK和抗体的Fab片段都阻断ODF与RANK的结合和ODF介导的破骨细胞生成。这些结果表明，RANK是ODF介导的破骨细胞生成所必需的信号受体。(C)北京：科学出版社.
Osteoclast differentiation factor (ODF) is a ligand for osteoclastogenesis-inhibitory factor/osteoprotegerin (OCIF/OPG), and mediates an essential signal for osteoclastogenesis. Soluble-form ODF binds directly to osteoclast progenitors, suggesting the presence of a membrane-bound receptor for ODF (ODFR) on the cells. To understand the ODF-mediated signal transduction mechanism in osteoclastogenesis, we molecularly cloned ODFR from a mouse macrophage-like osteoclast progenitor cell line, C7. Nucleotide sequence analysis revealed that ODFR is identical to RANK, a recently identified member of the tumor necrosis factor receptor (TNFR) family, which is involved in the regulation of dendritic cell function, A polyclonal antibody against the extracellular domain of RANK induced osteoclastogenesis in the presence of macrophage colony-stimulating factor (M-CSF). In contrast; both a genetically engineered soluble RANK and Fab fragment of the antibody blocked the binding of ODF to RANK and ODF-mediated osteoclastogenesis. These results indicate that RANK is the signaling receptor essential for ODF-mediated osteoclastogenesis. (C) 1998 Academic Press.