Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2
Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2
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DOI：
10.1016/j.mce.2012.05.002
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发表时间：
2012-09-25
影响因子：
4.1
通讯作者：
Nishida, Shozo
中科院分区：
文献类型：
--
作者：
Tsubaki, Masanobu;Satou, Takao;Nishida, Shozo
破骨细胞的分化受到NF-κ B B配体受体激活因子（RANKL）、巨噬细胞集落刺激因子（M-CSF）和CD 9的影响，这些因子在骨髓基质细胞和成骨细胞上表达。另外，骨保护素（OPG）被认为是破骨细胞生成抑制因子。在这项研究中，我们研究了双膦酸盐和他汀类药物是否增加OPG表达，并抑制骨髓源性基质细胞系ST 2中CD 9、M-CSF和RANKL的表达。我们发现，双膦酸盐和他汀类药物增强OPG mRNA的表达，抑制CD 9，M-CSF和RANKL mRNA的表达。氟替卡松、二膦酸盐和他汀类药物降低Ras和磷酸化ERK 1/2的膜定位，并激活p38 MAPK。这表明双膦酸盐和他汀类药物增强OPG表达，并抑制CD 9的表达。M-CSF和RANKL通过阻断Ras/ERK通路和激活p38 MAPK而发挥作用。因此，我们相信其临床应用将在未来的骨质疏松症治疗的发展进行研究。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Osteoclast differentiation is influenced by receptor activator of the NF-kappa B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and CD9, which are expressed on bone marrow stromal cells and osteoblasts. In addition, osteoprotegerin (OPG) is known as an osteoclastogenesis inhibitory factor. In this study, we investigated whether bisphosphonates and statins increase OPG expression and inhibit the expression of CD9, M-CSF, and RANKL in the bone marrow-derived stromal cell line ST2. We found that bisphosphonates and statins enhanced OPG mRNA expression and inhibited the expression of CD9, M-CSF, and RANKL mRNA. Futhermore, bisphosphonates and statins decreased the membrane localization of Ras and phosphorylated ERK1/2, and activated the p38MAPK. This indicates that bisphosphonates and statins enhanced OPG expression, and inhibited the expression of CD9. M-CSF, and RANKL through blocking the Ras/ERK pathway and activating p38MAPK. Accordingly, we believe that its clinical applications will be investigated in the future for the development of osteoporosis therapy. (c) 2012 Elsevier Ireland Ltd. All rights reserved.