PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function

Hyung Min Jeong; Yun Hye Jin; You Hee Choi; Jinah Yum; Joong Kook Choi; Chang Yeol Yeo; Kwang Youl Lee

doi:10.1016/j.bbamcr.2012.05.018

PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function

Hyung Min Jeong, Yun Hye Jin, You Hee Choi, Jinah Yum, Joong Kook Choi, Chang Yeol Yeo, Kwang Youl Lee

Department of Life Science

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little is known about its downstream effectors. We examined the effect of modulating PKC activity on osteogenic transcription factors and found that the protein level of Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays critical roles in bone formation and osteoblast differentiation. Here, we examined the role of PKC signaling in regulating the function of Msx2. We found that the inhibition of PKC signaling enhances osteogenic differentiation in BMP2-stimulated C2C12 cells. Treatment with inhibitors of PKC activity or overexpression of kinase-defective (KD), dominant-negative mutant PKC isoforms strongly reduced the level of Msx2 protein. Several PKC isoforms (α, β, δ, and *) interacted with Msx2, and PKCβ phosphorylated Msx2 at Thr135 and Thr141. Msx2 repressed the transcriptional activity of the osteogenic transcription factor Runx2, and this repression was relieved by inhibition of PKC activity or overexpression of the KD mutant PKC isoforms. In addition, PKC prolonged the half-life of Msx2 protein. These results suggest that PKC signaling modulates osteoblast differentiation, at least in part, through the regulation of Msx2.

Original language	English
Pages (from-to)	1225-1232
Number of pages	8
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1823
Issue number	8
DOIs	https://doi.org/10.1016/j.bbamcr.2012.05.018
State	Published - Aug 2012

Bibliographical note

Funding Information:
This work was supported by a Grant ( 2010–00266220 ) from the National Research Foundation of Korea to K.Y. Lee and by the Korea Research Foundation Grants funded by the Korean Government to C.-Y. Yeo ( KRF-2008-314-C00306 ), and by the Ewha Global Top 5 Grant 2011 of Ewha Womans University . J. Y. is supported by the second stage of the Brain Korea 21 project .

Keywords

Msx2
Osteoblast differentiation
PKC
Protein stability
Runx2

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title = "PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function",

abstract = "Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little is known about its downstream effectors. We examined the effect of modulating PKC activity on osteogenic transcription factors and found that the protein level of Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays critical roles in bone formation and osteoblast differentiation. Here, we examined the role of PKC signaling in regulating the function of Msx2. We found that the inhibition of PKC signaling enhances osteogenic differentiation in BMP2-stimulated C2C12 cells. Treatment with inhibitors of PKC activity or overexpression of kinase-defective (KD), dominant-negative mutant PKC isoforms strongly reduced the level of Msx2 protein. Several PKC isoforms (α, β, δ, and *) interacted with Msx2, and PKCβ phosphorylated Msx2 at Thr135 and Thr141. Msx2 repressed the transcriptional activity of the osteogenic transcription factor Runx2, and this repression was relieved by inhibition of PKC activity or overexpression of the KD mutant PKC isoforms. In addition, PKC prolonged the half-life of Msx2 protein. These results suggest that PKC signaling modulates osteoblast differentiation, at least in part, through the regulation of Msx2.",

keywords = "Msx2, Osteoblast differentiation, PKC, Protein stability, Runx2",

author = "Jeong, {Hyung Min} and Jin, {Yun Hye} and Choi, {You Hee} and Jinah Yum and Choi, {Joong Kook} and Yeo, {Chang Yeol} and Lee, {Kwang Youl}",

note = "Funding Information: This work was supported by a Grant ( 2010–00266220 ) from the National Research Foundation of Korea to K.Y. Lee and by the Korea Research Foundation Grants funded by the Korean Government to C.-Y. Yeo ( KRF-2008-314-C00306 ), and by the Ewha Global Top 5 Grant 2011 of Ewha Womans University . J. Y. is supported by the second stage of the Brain Korea 21 project .",

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AU - Jin, Yun Hye

AU - Choi, You Hee

AU - Yum, Jinah

AU - Choi, Joong Kook

AU - Yeo, Chang Yeol

AU - Lee, Kwang Youl

N1 - Funding Information: This work was supported by a Grant ( 2010–00266220 ) from the National Research Foundation of Korea to K.Y. Lee and by the Korea Research Foundation Grants funded by the Korean Government to C.-Y. Yeo ( KRF-2008-314-C00306 ), and by the Ewha Global Top 5 Grant 2011 of Ewha Womans University . J. Y. is supported by the second stage of the Brain Korea 21 project .

PY - 2012/8

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N2 - Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little is known about its downstream effectors. We examined the effect of modulating PKC activity on osteogenic transcription factors and found that the protein level of Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays critical roles in bone formation and osteoblast differentiation. Here, we examined the role of PKC signaling in regulating the function of Msx2. We found that the inhibition of PKC signaling enhances osteogenic differentiation in BMP2-stimulated C2C12 cells. Treatment with inhibitors of PKC activity or overexpression of kinase-defective (KD), dominant-negative mutant PKC isoforms strongly reduced the level of Msx2 protein. Several PKC isoforms (α, β, δ, and *) interacted with Msx2, and PKCβ phosphorylated Msx2 at Thr135 and Thr141. Msx2 repressed the transcriptional activity of the osteogenic transcription factor Runx2, and this repression was relieved by inhibition of PKC activity or overexpression of the KD mutant PKC isoforms. In addition, PKC prolonged the half-life of Msx2 protein. These results suggest that PKC signaling modulates osteoblast differentiation, at least in part, through the regulation of Msx2.

AB - Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little is known about its downstream effectors. We examined the effect of modulating PKC activity on osteogenic transcription factors and found that the protein level of Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays critical roles in bone formation and osteoblast differentiation. Here, we examined the role of PKC signaling in regulating the function of Msx2. We found that the inhibition of PKC signaling enhances osteogenic differentiation in BMP2-stimulated C2C12 cells. Treatment with inhibitors of PKC activity or overexpression of kinase-defective (KD), dominant-negative mutant PKC isoforms strongly reduced the level of Msx2 protein. Several PKC isoforms (α, β, δ, and *) interacted with Msx2, and PKCβ phosphorylated Msx2 at Thr135 and Thr141. Msx2 repressed the transcriptional activity of the osteogenic transcription factor Runx2, and this repression was relieved by inhibition of PKC activity or overexpression of the KD mutant PKC isoforms. In addition, PKC prolonged the half-life of Msx2 protein. These results suggest that PKC signaling modulates osteoblast differentiation, at least in part, through the regulation of Msx2.

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KW - Osteoblast differentiation

KW - PKC

KW - Protein stability

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JF - Biochimica et Biophysica Acta - Molecular Cell Research

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PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function

Abstract

Bibliographical note

Keywords

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