RANKL-induced DC-STAMP is essential for osteoclastogenesis.

RANKL-induced DC-STAMP is essential for osteoclastogenesis.
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DOI:
10.1084/jem.20040518
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发表时间:
2004-10-04
影响因子:
15.3
通讯作者:
Nomiyama, H
Nomiyama, H
中科院分区:
医学1区
文献类型:
--
作者:
Kukita, T;Wada, N;Kukita, A;Kakimoto, T;Sandra, F;Toh, K;Nagata, K;Iijima, T;Horiuchi, M;Matsusaki, H;Hieshima, K;Yoshie, O;Nomiyama, H

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破骨细胞是骨吸收的多核巨细胞,对骨重塑至关重要,是通过单核前体细胞的细胞融合形成的。尽管核因子κB配体受体激活剂(RANKL)已被证明是一种重要的破骨细胞因子,但参与破骨细胞形成的细胞表面分子大多未知。在这里,我们报告七次跨膜受体样分子、树突状细胞特异性跨膜蛋白(DC-STAMP)参与破骨细胞生成。 RANKL 和其他破骨细胞生成刺激可在破骨细胞前体细胞中快速诱导 DC-STAMP 的表达。小干扰RNA和特异性抗体对DC-STAMP的靶向抑制显着抑制了多核破骨细胞样细胞的形成。 DC-STAMP 的过表达在 RANKL 存在下增强破骨细胞生成。此外,DC-STAMP直接诱导破骨细胞标志物抗酒石酸酸性磷酸酶的表达。这些数据首次证明 DC-STAMP 在破骨细胞生成中具有重要作用。
Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Although receptor activator of nuclear factor–κB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the cell surface molecules involved in osteoclastogenesis are mostly unknown. Here, we report that the seven-transmembrane receptor-like molecule, dendritic cell–specific transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of DC-STAMP is rapidly induced in osteoclast precursor cells by RANKL and other osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small interfering RNAs and specific antibody markedly suppressed the formation of multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly induced the expression of the osteoclast marker tartrate-resistant acid phosphatase. These data demonstrate for the first time that DC-STAMP has an essential role in osteoclastogenesis.
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