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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

The induction of c-Fos in RAW264.7D clone cells was inhibited by BIX02189 or XMD8-92.(A) RAW264.7D clone cells (2.5 × 104) were cultured in the presence of sRANKL (50 ng/ml) with or without BIX02189 or XMD8-92. After 20 hrs, c-Fos gene expression was measured by qRT-PCR. Similar results were obtained in two independent experiments. *P<0.05 when compared with the culture with sRANKL. (B) RAW264.7D clone cells (2.5 × 104) were cultured with sRANKL (50 ng/ml). Subsequently, 5 μM BIX02189 or 1μM XMD8-92 was added to the samples, and c-Fos gene expression was examined after 6 hrs by Western blot analysis.
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pone.0125054.g008: The induction of c-Fos in RAW264.7D clone cells was inhibited by BIX02189 or XMD8-92.(A) RAW264.7D clone cells (2.5 × 104) were cultured in the presence of sRANKL (50 ng/ml) with or without BIX02189 or XMD8-92. After 20 hrs, c-Fos gene expression was measured by qRT-PCR. Similar results were obtained in two independent experiments. *P<0.05 when compared with the culture with sRANKL. (B) RAW264.7D clone cells (2.5 × 104) were cultured with sRANKL (50 ng/ml). Subsequently, 5 μM BIX02189 or 1μM XMD8-92 was added to the samples, and c-Fos gene expression was examined after 6 hrs by Western blot analysis.

Mentions: The induction of c-Fos was also examined in RAW264.7D clone cells. Similarly to the 4B12 cells, c-Fos was induced in RAW264.7D clone cells in response to sRANKL stimulation. This phenomenon was blocked by BIX02189 or XMD8-92 in RAW264.7D clone cells (Fig 8), suggesting that activation of the ERK5 pathway was required for the induction of c-Fos.


ERK5 activation is essential for osteoclast differentiation.

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

The induction of c-Fos in RAW264.7D clone cells was inhibited by BIX02189 or XMD8-92.(A) RAW264.7D clone cells (2.5 × 104) were cultured in the presence of sRANKL (50 ng/ml) with or without BIX02189 or XMD8-92. After 20 hrs, c-Fos gene expression was measured by qRT-PCR. Similar results were obtained in two independent experiments. *P<0.05 when compared with the culture with sRANKL. (B) RAW264.7D clone cells (2.5 × 104) were cultured with sRANKL (50 ng/ml). Subsequently, 5 μM BIX02189 or 1μM XMD8-92 was added to the samples, and c-Fos gene expression was examined after 6 hrs by Western blot analysis.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0125054.g008: The induction of c-Fos in RAW264.7D clone cells was inhibited by BIX02189 or XMD8-92.(A) RAW264.7D clone cells (2.5 × 104) were cultured in the presence of sRANKL (50 ng/ml) with or without BIX02189 or XMD8-92. After 20 hrs, c-Fos gene expression was measured by qRT-PCR. Similar results were obtained in two independent experiments. *P<0.05 when compared with the culture with sRANKL. (B) RAW264.7D clone cells (2.5 × 104) were cultured with sRANKL (50 ng/ml). Subsequently, 5 μM BIX02189 or 1μM XMD8-92 was added to the samples, and c-Fos gene expression was examined after 6 hrs by Western blot analysis.
Mentions: The induction of c-Fos was also examined in RAW264.7D clone cells. Similarly to the 4B12 cells, c-Fos was induced in RAW264.7D clone cells in response to sRANKL stimulation. This phenomenon was blocked by BIX02189 or XMD8-92 in RAW264.7D clone cells (Fig 8), suggesting that activation of the ERK5 pathway was required for the induction of c-Fos.

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