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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 TRAP activity in Raw264.7D clone cells was inhibited with BIX02189 or XMD8-92.RAW264.7D clone cells (5 × 103) were treated with BIX02189 (A) or XMD8-92 (B) in the presence of sRANKL (10 ng/ml). After 6 days, the TRAP activity was measured. Both BIX02189 and XMD8-92 inhibited TRAP activity in RAW264.7D clone cells. *P<0.05 compared with the culture without inhibitors.
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pone.0125054.g007: The TRAP activity in Raw264.7D clone cells was inhibited with BIX02189 or XMD8-92.RAW264.7D clone cells (5 × 103) were treated with BIX02189 (A) or XMD8-92 (B) in the presence of sRANKL (10 ng/ml). After 6 days, the TRAP activity was measured. Both BIX02189 and XMD8-92 inhibited TRAP activity in RAW264.7D clone cells. *P<0.05 compared with the culture without inhibitors.

Mentions: The differentiation of RAW264.7D clone cells was also activated by sRANKL, and M-CSF was not required for this process. The behavior of the RAW264.7D clone cells was examined during MEK5/ERK5 pathway inhibition. Inhibition of the MEK5 pathway reduced the formation of TRAP-positive MNCs (Fig 6A). Inhibition of the ERK5 pathway also reduced it (Fig 6B). ERK5 was constitutively activated (see the control lane in the Figure), and the activation of ERK5 was inhibited by BIX02189 (Fig 6C). ERK1 and 2 were not inhibited in these cells (Fig 6C). The viability of the cells was not affected by the drug treatments (Fig 6D). MEK5/ERK5 pathway inhibitors also reduced TRAP activity (Fig 7), which suggested that activation of the ERK5 pathway was required for the differentiation of RAW264.7D clone cells.


ERK5 activation is essential for osteoclast differentiation.

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

The TRAP activity in Raw264.7D clone cells was inhibited with BIX02189 or XMD8-92.RAW264.7D clone cells (5 × 103) were treated with BIX02189 (A) or XMD8-92 (B) in the presence of sRANKL (10 ng/ml). After 6 days, the TRAP activity was measured. Both BIX02189 and XMD8-92 inhibited TRAP activity in RAW264.7D clone cells. *P<0.05 compared with the culture without inhibitors.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0125054.g007: The TRAP activity in Raw264.7D clone cells was inhibited with BIX02189 or XMD8-92.RAW264.7D clone cells (5 × 103) were treated with BIX02189 (A) or XMD8-92 (B) in the presence of sRANKL (10 ng/ml). After 6 days, the TRAP activity was measured. Both BIX02189 and XMD8-92 inhibited TRAP activity in RAW264.7D clone cells. *P<0.05 compared with the culture without inhibitors.
Mentions: The differentiation of RAW264.7D clone cells was also activated by sRANKL, and M-CSF was not required for this process. The behavior of the RAW264.7D clone cells was examined during MEK5/ERK5 pathway inhibition. Inhibition of the MEK5 pathway reduced the formation of TRAP-positive MNCs (Fig 6A). Inhibition of the ERK5 pathway also reduced it (Fig 6B). ERK5 was constitutively activated (see the control lane in the Figure), and the activation of ERK5 was inhibited by BIX02189 (Fig 6C). ERK1 and 2 were not inhibited in these cells (Fig 6C). The viability of the cells was not affected by the drug treatments (Fig 6D). MEK5/ERK5 pathway inhibitors also reduced TRAP activity (Fig 7), which suggested that activation of the ERK5 pathway was required for the differentiation of RAW264.7D clone cells.

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