| First Author | Yoshida K | Year | 2012 |
| Journal | Mol Cell Endocrinol | Volume | 361 |
| Issue | 1-2 | Pages | 99-105 |
| PubMed ID | 22484461 | Mgi Jnum | J:189443 |
| Mgi Id | MGI:5445822 | Doi | 10.1016/j.mce.2012.03.019 |
| Citation | Yoshida K, et al. (2012) PKR plays a positive role in osteoblast differentiation by regulating GSK-3beta activity through a beta-catenin-independent pathway. Mol Cell Endocrinol 361(1-2):99-105 |
| abstractText | Double-stranded RNA-dependent protein kinase (PKR) is involved in various cellular functions. We previously reported that PKR regulates osteoblast differentiation, but the specific mechanisms by which this occurs remain unclear. In this study, we investigated the role of PKR in Glycogen synthase kinase 3beta (GSK-3beta) regulation of osteoblast differentiation. Lithium chloride (LiCl), a GSK-3beta inhibitor, increased GSK-3beta phosphorylation in MC3T3-E1 and MG-63 cells. LiCl also inhibited Runx2 and expression of its regulated genes, causing inhibition of Alkaline phosphatase activity and mineralization. LiCl injection to the calvaria in mice suppressed bone formation. Further, GSK-3beta phosphorylation was increased in osteoblasts, by Akt-independent mechanisms, in which PKR was constitutively inactivated. A PKR inhibitor, 2-aminopurine, also induced GSK-3beta phosphorylation in MC3T3-E1 and MG-63 cells. Further, Runx2 and its regulated genes were inhibited in PKR-inactivated osteoblasts, and differentiation was suppressed through a beta-catenin-independent pathway. PKR positively regulates the differentiation of osteoblasts by mediating GSK-3beta activity through a beta-catenin-independent pathway. |
