诱饵受体3（DcR3）可诱导单核细胞/巨噬细胞谱系前体细胞形成破骨细胞。
Decoy receptor 3 (DcR3) induces osteoclast formation from monocyte/macrophage lineage precursor cells.
作者信息
Yang C R, Wang J H, Hsieh S L, Wang S M, Hsu T L, Lin W W
机构信息
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
出版信息
Cell Death Differ. 2004 Jul;11 Suppl 1:S97-107. doi: 10.1038/sj.cdd.4401403.
Recent evidence indicates that the decoy receptor 3 (DcR3) of the TNF receptor superfamily, which initially though prevents cytokine responses of FasL, LIGHT and TL1A by binding and neutralization, can modulate monocyte function through reverse signaling. We show in this work that DcR3 can induce osteoclast formation from human monocytes, murine RAW264.7 macrophages, and bone marrow cells. DcR3-differentiated cells exhibit characteristics unique for osteoclasts, including polynuclear giant morphology, bone resorption, TRAP, CD51/61, and MMP-9 expression. Consistent with the abrogation of osteoclastogenic effect of DcR3 by TNFR-Fc, DcR3 treatment can induce osteoclastogenic cytokine TNF-alpha release through ERK and p38 MAPK signaling pathways. We conclude that DcR3 via coupling reverse signaling of ERK and p38 MAPK and stimulating TNF-alpha synthesis is a critical regulator of osteoclast formation. This action of DcR3 might play an important role in significant osteoclastic activity in osteolytic bone metastases.
最近的证据表明，肿瘤坏死因子受体超家族的诱饵受体3（DcR3）最初被认为通过结合和中和来阻止FasL、LIGHT和TL1A的细胞因子反应，但它可以通过反向信号传导调节单核细胞功能。我们在这项研究中表明，DcR3可以诱导人单核细胞、小鼠RAW264.7巨噬细胞和骨髓细胞形成破骨细胞。DcR3分化的细胞表现出破骨细胞特有的特征，包括多核巨细胞形态、骨吸收、抗酒石酸酸性磷酸酶（TRAP）、CD51/61和基质金属蛋白酶-9（MMP-9）表达。与TNFR-Fc消除DcR3的破骨细胞生成作用一致，DcR3处理可通过ERK和p38丝裂原活化蛋白激酶（MAPK）信号通路诱导破骨细胞生成细胞因子肿瘤坏死因子-α（TNF-α）释放。我们得出结论，DcR3通过耦合ERK和p38 MAPK的反向信号传导并刺激TNF-α合成，是破骨细胞形成的关键调节因子。DcR3的这一作用可能在溶骨性骨转移中显著增强的破骨细胞活性中发挥重要作用。
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