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ERK5 activation is essential for osteoclast differentiation.

Amano S, Chang YT, Fukui Y - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Keyakidai, Sakado City, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

ERK5 was activated by M-CSF in 4B12 cells.(A, B) 4B12 cells were stimulated with 20 ng/ml M-CSF or 100 ng/ml sRANKL, and the phosphorylation of ERK5 was examined by Western blot analysis. Similar results were obtained in two independent experiments.
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pone.0125054.g001: ERK5 was activated by M-CSF in 4B12 cells.(A, B) 4B12 cells were stimulated with 20 ng/ml M-CSF or 100 ng/ml sRANKL, and the phosphorylation of ERK5 was examined by Western blot analysis. Similar results were obtained in two independent experiments.

Mentions: The activation of ERK5 in 4B12 cells treated with M-CSF or sRANKL was examined. ERK5 was activated by M-CSF but not by sRANKL. The ERK5 activation was detected as early as 5 min after M-CSF stimulation and continued for a long duration (Fig 1A and 1B).


ERK5 activation is essential for osteoclast differentiation.

Amano S, Chang YT, Fukui Y - PLoS ONE (2015)

ERK5 was activated by M-CSF in 4B12 cells.(A, B) 4B12 cells were stimulated with 20 ng/ml M-CSF or 100 ng/ml sRANKL, and the phosphorylation of ERK5 was examined by Western blot analysis. Similar results were obtained in two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401765&req=5

pone.0125054.g001: ERK5 was activated by M-CSF in 4B12 cells.(A, B) 4B12 cells were stimulated with 20 ng/ml M-CSF or 100 ng/ml sRANKL, and the phosphorylation of ERK5 was examined by Western blot analysis. Similar results were obtained in two independent experiments.
Mentions: The activation of ERK5 in 4B12 cells treated with M-CSF or sRANKL was examined. ERK5 was activated by M-CSF but not by sRANKL. The ERK5 activation was detected as early as 5 min after M-CSF stimulation and continued for a long duration (Fig 1A and 1B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Keyakidai, Sakado City, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus