骨芽細胞の分化におけるPKRの役割について

In this study, it was demonstrated that double-stranded RNA-dependent protein kinase (PKR) is required for the differentiation of osteoblasts. PKR was expressed on the surface of trabecula in rat tibiae. Dominant-negative mutant PKR cDNA, in which the amino acid lysine at 296 was replaced with arginine and which did not have catalytic activity, was transfected into mouse osteoblastic MC3T3-E1 cells; thereby establishing cells that stably expressed the PKR mutant gene (PKR-K/R). PKR-K/R mutant cells exhibited up-regulated cell growth and had low alkaline phosphatase (ALP) activity. PKR-K/R mutant cells were not able to form bone nodules in vitro. The expression of STAT1α protein increased in PKR-K/R mutant cells, in which runt-related gene 2 (Runx2)-mediated transcription decreased compared with the levels in control cells. When the expression of STAT1α protein in PKR mutant cells was suppressed in the presence of STAT1α siRNA, the activity of Runx2-mediated transcription recovered to the control level. These results indicate that PKR is a stimulator of Runx2 transcription and is a negative modulator of STAT1α expression. These findings also suggest that PKR plays important roles in the differentiation and calcification of osteoblasts by modulating STAT1α and/or Runx2 expression.