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

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19 Scopus citations


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 languageEnglish
Pages (from-to)1225-1232
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number8
StatePublished - 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 .


  • Msx2
  • Osteoblast differentiation
  • PKC
  • Protein stability
  • Runx2


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