Targeting extracellular signal-regulated kinase (ERK) signaling has therapeutic implications for inflammatory osteolysis.
Targeting extracellular signal-regulated kinase (ERK) signaling has therapeutic implications for inflammatory osteolysis.
复制标题
DOI：
10.1016/j.bone.2009.10.032
复制
发表时间：
2010-03
期刊：
影响因子：
4.1
通讯作者：
Lee, Francis Y.
中科院分区：
文献类型：
--
作者：
Seo, Sung Wook;Lee, Daniel;Minematsu, Hiroshi;Kim, Abraham D.;Shin, Mike;Cho, Samuel K.;Kim, Dae Won;Yang, Jay;Lee, Francis Y.
关键词：
细胞外信号调节激酶1/2（ERK）通路是丝裂原活化蛋白激酶（MAPK）家族的一部分，其在细胞分化和增殖中的作用是众所周知的。在破骨细胞生成的背景下，巨噬细胞集落刺激因子（M-CSF）是ERK的上游激活剂，其在破骨细胞前体分化成多核破骨细胞之前发出存活的信号。此外，最近的许多研究表明ERK参与促进骨质溶解。在这项研究中，我们通过鉴定ERK通路作为破骨细胞和巨噬细胞中骨质溶解的主要通路，扩展了这些现有的将ERK和骨质溶解联系起来的发现。我们还阐明了促炎能力的成骨细胞使用ERK途径。此外，ERK抑制剂PD 98059在局部和全身水平上抑制所有三种细胞类型传播的炎症反应。ERK信号在先前已知的介导炎性骨质溶解的细胞类型中的重要性以及涉及ERK信号的成骨细胞先天性免疫的发现增强了我们对炎性骨质溶解的理解，并支持针对ERK通路的靶向治疗用于治疗骨质溶解性疾病的进一步未来研究。
The extracellular signal-regulated kinase 1/2 (ERK) pathway, part of the mitogen-activated protein kinase (MAPK) family, is well-known for its role in cell differentiation and proliferation. In the context of osteoclastogenesis, macrophage colony stimulating factor (M-CSF) is an upstream activator of ERK, which signals for the survival of osteoclast precursors prior to their differentiation into multinucleated osteoclasts. In addition, many recent studies have revealed the involvement of ERK in promoting osteolysis. In this study, we extended these existing findings linking ERK and osteolysis by identifying the ERK pathway as the primary pathway for osteolysis in osteoclasts and macrophages. We also elucidated the pro-inflammatory capacity of osteoblasts using the ERK pathway. Moreover, the ERK inhibitor, PD98059, inhibited the inflammatory reaction propagated by all three cell types at both a local and systemic level. The importance of ERK signaling in previously known cell types mediating inflammatory osteolysis as well as the discovery of osteoblastic innate immunity involving ERK signaling enhances our understanding of inflammatory osteolysis and supports further future investigation of targeted therapies against the ERK pathway for treating osteolytic diseases.
登录
查看更多内容
DOI：
10.1152/ajpcell.1998.274.6.c1686
发表时间：
1998-06-01
影响因子：
5.5
作者：
Tam, VK;Schotland, S;Green, J
通讯作者：
Green, J
影响因子：
64.8
作者：
Takayanagi, H;Ogasawara, K;Taniguchi, T
通讯作者：
Taniguchi, T
DOI：
10.1006/bbrc.1999.1623
发表时间：
1999-11-11
影响因子：
3.1
作者：
Horwood, NJ;Kartsogiannis, V;Gillespie, MT
通讯作者：
Gillespie, MT
影响因子：
29
作者：
Elefteriou, Florent;Benson, M. Douglas;Karsenty, Gerard
通讯作者：
Karsenty, Gerard
影响因子：
6.1
作者：
Tanaka, H;Tanabe, N;Maeno, M
通讯作者：
Maeno, M