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TRAF6 依赖的信号通路对于 TNF 相关凋亡诱导配体（TRAIL）诱导破骨细胞分化是必需的。

TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand (TRAIL) induces osteoclast differentiation.

机构信息

Department of General Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

PLoS One. 2012;7(6):e38048. doi: 10.1371/journal.pone.0038048. Epub 2012 Jun 14.

DOI:10.1371/journal.pone.0038048
PMID:22719861
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3375273/
Abstract

Human osteoclast formation from mononuclear phagocyte precursors involves interactions between tumor necrosis factor (TNF) ligand superfamily members and their receptors. Recent evidence indicates that in addition to triggering apoptosis, the TNF-related apoptosis-inducing ligand (TRAIL) induces osteoclast differentiation. To understand TRAIL-mediated signal transduction mechanism in osteoclastogenesis, we demonstrated that TRAIL induces osteoclast differentiation via a Tumor necrosis factor receptor-associated factor 6 (TRAF-6)-dependent signaling pathway. TRAIL-induced osteoclast differentiation was significantly inhibited by treatment with TRAF-6 siRNA and TRAF6 decoy peptides in both human monocytes and murine RAW264.7 macrophage cell lines, as evaluated in terms of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and bone resorption activity. Moreover, TRAIL-induced osteoclast differentiation was also abolished in TRAF6 knockout bone marrow macrophages. In addition to induction of NFATc1, treatment of TRAIL also induced ubiquitination of TRAF6 in osteoclast differentiation. Thus, our data demonstrate that TRAIL induces osteoclastic differentiation via a TRAF-6 dependent signaling pathway. This study suggests TRAF6-dependent signaling may be a central pathway in osteoclast differentiation, and that TNF superfamily molecules other than RANKL may modify RANK signaling by interaction with TRAF6-associated signaling.

摘要

人破骨细胞从单核吞噬细胞前体的形成涉及肿瘤坏死因子（TNF）配体超家族成员及其受体之间的相互作用。最近的证据表明，除了触发细胞凋亡外，TNF 相关凋亡诱导配体（TRAIL）还诱导破骨细胞分化。为了了解 TRAIL 介导的破骨细胞分化中的信号转导机制，我们证明 TRAIL 通过肿瘤坏死因子受体相关因子 6（TRAF-6）依赖性信号通路诱导破骨细胞分化。TRAIL 诱导的破骨细胞分化在人单核细胞和鼠 RAW264.7 巨噬细胞系中均被 TRAF-6 siRNA 和 TRAF6 诱饵肽处理显著抑制，根据抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞和骨吸收活性进行评估。此外，TRAF6 基因敲除骨髓巨噬细胞中也消除了 TRAIL 诱导的破骨细胞分化。除了诱导 NFATc1 外，TRAIL 处理还诱导破骨细胞分化中 TRAF6 的泛素化。因此，我们的数据表明 TRAIL 通过 TRAF-6 依赖性信号通路诱导破骨细胞分化。这项研究表明 TRAF6 依赖性信号可能是破骨细胞分化的中心途径，并且 RANKL 以外的 TNF 超家族分子可能通过与 TRAF6 相关信号的相互作用来修饰 RANK 信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/c4d3f768f278/pone.0038048.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/47afe4b63f98/pone.0038048.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/95366510895c/pone.0038048.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/a61fa3e9acf4/pone.0038048.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/af424be77639/pone.0038048.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/021d66cbec9f/pone.0038048.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/c4d3f768f278/pone.0038048.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/47afe4b63f98/pone.0038048.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/95366510895c/pone.0038048.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/a61fa3e9acf4/pone.0038048.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/af424be77639/pone.0038048.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/021d66cbec9f/pone.0038048.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c1/3375273/c4d3f768f278/pone.0038048.g006.jpg

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