| First Author | Jeong HM | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1823 |
| Issue | 8 | Pages | 1225-32 |
| PubMed ID | 22633971 | Mgi Jnum | J:188072 |
| Mgi Id | MGI:5439073 | Doi | 10.1016/j.bbamcr.2012.05.018 |
| Citation | Jeong HM, et al. (2012) PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function. Biochim Biophys Acta 1823(8):1225-32 |
| abstractText | 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 (alpha, beta, delta, and zeta) interacted with Msx2, and PKCbeta 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. |
