CXCL2 mediates lipopolysaccharide-induced osteoclastogenesis in RANKL-primed precursors
CXCL2 mediates lipopolysaccharide-induced osteoclastogenesis in RANKL-primed precursors
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DOI：
10.1016/j.cyto.2011.03.026
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发表时间：
2011-07-01
期刊：
影响因子：
3.8
通讯作者：
Kim, Hong-Hee
中科院分区：
文献类型：
--
作者：
Ha, Jeongim;Lee, Youngkyun;Kim, Hong-Hee
强炎症剂脂多糖（LPS）已被证明在体内引起骨溶解。然而，脂多糖诱导的骨破坏的病因仍然是难以捉摸的。在这里，我们发现LPS在转录水平上刺激骨髓巨噬细胞（BMMs）（破骨细胞前体）中CXCL2的诱导，即使在没有合成新蛋白（包括干扰素β）的情况下，活性氧参与CXCL2的分泌，但不参与mRNA的表达。LPS对CXCL2 mRNA的诱导通过p38、JNK和NF κ B信号通路介导。此外，c-Fos和p65被直接募集到CXCL2启动子上。lps处理的bmm条件培养基可以增强破骨细胞前体的迁移，而cxcl2中和抗体或CXCR2受体拮抗剂可以阻断这种迁移。CXCL2的阻断也减少了lps诱导的破骨细胞生成。更重要的是，cxcl2中和可以防止LPS处理小鼠的骨破坏。因此，CXCL2可能是炎性骨破坏性疾病的有效治疗靶点。(C) 2011 Elsevier Ltd.版权所有。
The strong inflammatory agent lipopolysaccharide (LPS) has been shown to cause bone lysis in vivo. However, the etiology of LPS-induced bone destruction is still elusive. Here, we show that LPS stimulates the induction of CXCL2 in bone marrow macrophages (BMMs), osteoclast precursors, at the transcription level even in the absence of the synthesis of new proteins including interferon beta Reactive oxygen species were involved in the secretion of CXCL2 but not in the mRNA expression. CXCL2 mRNA induction by LPS was mediated by p38, JNK, and NF kappa B signaling pathways. Moreover, c-Fos and p65 were directly recruited to CXCL2 promoter. The conditioned medium from LPS-treated BMMs could enhance migration of osteoclast precursors, which was blocked by treatment with CXCL2-neutralizing antibody or CXCR2 receptor antagonist. The blockade of CXCL2 also reduced LPS-induced osteoclastogenesis. More significantly, CXCL2-neutralization prevented bone destruction in mice treated with LPS. Therefore, CXCL2 might be a useful therapeutic target for inflammatory bone destructive diseases. (C) 2011 Elsevier Ltd. All rights reserved.