ERK5 activation is essential for osteoclast differentiation.
ERK5 activation is essential for osteoclast differentiation.
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DOI：
10.1371/journal.pone.0125054
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fukui Y
中科院分区：
文献类型：
--
作者：
Amano S;Chang YT;Fukui Y
MEK/ERK通路对控制细胞增殖和分化至关重要。在本研究中，我们发现MEK5/ERK5通路参与破骨细胞分化。ERK5被M-CSF激活，是破骨细胞分化的重要因子之一。BIX02189抑制MEK5或XMD 8-92抑制ERK5可阻断破骨细胞分化。MEK5敲低抑制破骨细胞分化。RAW264.7D克隆细胞为单核细胞，经sRANKL刺激后分化为破骨细胞。在这些细胞中，ERK5在没有任何刺激的情况下被激活。这些抑制剂对MEK5/ERK5通路的抑制也阻断了RAW264.7D细胞向破骨细胞的分化。此外，MEK5或ERK5抑制剂抑制了破骨细胞分化不可或缺的转录因子c-Fos的表达。因此，c-Fos的诱导需要ERK5的激活。这些事件在m - csf依赖性骨髓巨噬细胞的实验中得到证实。综上所述，目前的结果表明，用M-CSF激活MEK5/ERK5通路是破骨细胞分化所必需的，这可能通过诱导c-Fos来诱导分化。
The MEK/ERK pathways are critical for controlling cell proliferation and differentiation. In this study, we show that the MEK5/ERK5 pathway participates in osteoclast differentiation. ERK5 was activated by M-CSF, which is one of the essential factors in osteoclast differentiation. Inhibition of MEK5 by BIX02189 or inhibition of ERK5 by XMD 8-92 blocked osteoclast differentiation. MEK5 knockdown inhibited osteoclast differentiation. RAW264.7D clone cells, which are monocytic cells, differentiate into osteoclasts after stimulation with sRANKL. ERK5 was activated without any stimulation in these cells. Inhibition of the MEK5/ERK5 pathway by the inhibitors also blocked the differentiation of RAW264.7D cells into osteoclasts. Moreover, expression of the transcription factor c-Fos, which is indispensable for osteoclast differentiation, was inhibited by treatment with MEK5 or ERK5 inhibitors. Therefore, activation of ERK5 is required for the induction of c-Fos. These events were confirmed in experiments using M-CSF-dependent bone marrow macrophages. Taken together, the present results show that activation of the MEK5/ERK5 pathway with M-CSF is required for osteoclast differentiation, which may induce differentiation through the induction of c-Fos.
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影响因子：
4
作者：
Watanabe, T;Kukita, T;Iijima, T
通讯作者：
Iijima, T
影响因子：
15.3
作者：
Kukita, T;Wada, N;Kukita, A;Kakimoto, T;Sandra, F;Toh, K;Nagata, K;Iijima, T;Horiuchi, M;Matsusaki, H;Hieshima, K;Yoshie, O;Nomiyama, H
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Nomiyama, H
影响因子：
29.4
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Todisco A
影响因子：
5.6
作者：
Amano, Shigeru;Sekine, Keisuke;Ohmori, Yoshihiro
通讯作者：
Ohmori, Yoshihiro
影响因子：
4.8
作者：
Meadows, Nicholas A.;Sharma, Sudarshana M.;Cassady, Alan I.
通讯作者：
Cassady, Alan I.